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Burgos-Burgos J, Vega V, Macias-Verde D, Vicente E, Murias C, Santana C, Lara PC. IORT-photon boost plus hypofractionated whole breast irradiation in patients with breast cancer after primary systemic treatment: feasibility, safety and clinical results. Clin Transl Oncol 2024:10.1007/s12094-024-03759-z. [PMID: 39466580 DOI: 10.1007/s12094-024-03759-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 10/04/2024] [Indexed: 10/30/2024]
Abstract
AIM To assess for the first time the safety and feasibility of combining photon-intraoperative radiotherapy (ph-IORT) with hypofractionated whole breast irradiation (h-WBI) in patients referred to primary systemic therapy (PST). METHODS From March 2019 to December 2020, patients referred for breast conservative surgery (BCS) after PST in our institution were prospectively included in the present trial. PST was prescribed to all patients according the ESMO-SEOM guidelines. Once the PST was completed, BCS was discussed in the multidisciplinary tumor board (MTB). 20 Gy were prescribed to the surface of the applicator of an Intrabeam®photon-IORT during BCS. h-WBI (40.5 Gy/2.67 Gy/15frx) was planned to be administered 3-5w after BCS. All patients were treated with hWBI VMAT-Rapid-Arc&Daily Exac-Trac-IGRT. The primary end points of the study were feasibility and safety (grade 3 toxicity rate CTCAE.5.0-scale) of the proposed treatment protocol. The secondary end points included cosmetic results (Harvard Scale), local relapse rate and overall survival. RESULTS Thirty-five patients were included in the trial. The median age was 54 years. Tumor size was > 2 cm in all cases. Eighteen patients were N + (51.4%). There was no disease progression during PST. All patients received the planned 20 Gy-ph-IORT boost at the time of BCS and the proposed h-WBI. 31/35 (88,6%) patients started h-WBI within the predefined time period (3-5w after BCS). No patient showed ≥ G3 acute toxicity 3 months after the end of h-WBI. No ≥ G3 late toxicity was observed at 12 months of follow-up and thereafter. Cosmetic results were scored excellent/good in 26 patients (74.2%). After a median follow-up of 52 months, a TNBC patient locally relapsed at 13 months of follow-up. CONCLUSION We demonstrated for the first time that ph-IORT + hWBI is feasible and safe in patients referred to BCS after PST.
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Affiliation(s)
- J Burgos-Burgos
- Centro Oncologico Integral Canario, Hospital Universitario San Roque, Universidad Fernando Pessoa Canarias, Insituto Canario de Investigación del Cáncer, Las Palmas, Spain
| | - V Vega
- Centro Oncologico Integral Canario, Hospital Universitario San Roque, Universidad Fernando Pessoa Canarias, Insituto Canario de Investigación del Cáncer, Las Palmas, Spain
| | - D Macias-Verde
- Centro Oncologico Integral Canario, Hospital Universitario San Roque, Universidad Fernando Pessoa Canarias, Insituto Canario de Investigación del Cáncer, Las Palmas, Spain
| | - E Vicente
- Centro Oncologico Integral Canario, Hospital Universitario San Roque, Universidad Fernando Pessoa Canarias, Insituto Canario de Investigación del Cáncer, Las Palmas, Spain
| | - C Murias
- Centro Oncologico Integral Canario, Hospital Universitario San Roque, Universidad Fernando Pessoa Canarias, Insituto Canario de Investigación del Cáncer, Las Palmas, Spain
| | - C Santana
- Centro Oncologico Integral Canario, Hospital Universitario San Roque, Universidad Fernando Pessoa Canarias, Insituto Canario de Investigación del Cáncer, Las Palmas, Spain
| | - P C Lara
- Centro Oncologico Integral Canario, Hospital Universitario San Roque, Universidad Fernando Pessoa Canarias, Insituto Canario de Investigación del Cáncer, Las Palmas, Spain.
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Dave S, Choudhury A, Alurkar SS, Shah AM. Is Ki-67 Really Useful as a Predictor for Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer? Indian J Surg Oncol 2024; 15:44-52. [PMID: 38511030 PMCID: PMC10948718 DOI: 10.1007/s13193-023-01822-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 09/21/2023] [Indexed: 03/22/2024] Open
Abstract
Neoadjuvant chemotherapy (NACT) is routinely offered to operable locally advanced breast cancer (LABC) patients desirous of breast conservation surgery and inoperable LABC patients. Pathological complete response (pCR) following chemotherapy is recognized as a surrogate for survival outcomes in high grade tumour subtypes. Many biological and tumor characters have been shown to predict pCR. The current study was performed with the aim of investigating the ability of Ki-67 in predicting pCR with NACT in breast cancer patients. A total of 105 patients with locally advanced breast cancer who completed NACT followed by surgery were included in this study from January 2020 till December 2022. Patients with advanced metastatic breast carcinoma, who did not give consent for NACT, who did not complete NACT and who did not undergo surgery were excluded. All patients were assessed for Ki-67 score on core-needle biopsy samples and response rate was assessed clinically and by histopathological examination of resected specimen. Quantitative variables were compared using unpaired t-test or Mann-Whitney 'U' test and for categorical variables Chi-square or Fisher's exact test were used. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive potential of Ki-67 expression levels in predicting pCR. To identify the predictive factors associated with pCR, univariate analysis was performed. The P value < 0.05 was considered as statistically significant. Mean age was 51.57 ± 10.8 years. 51 patients achieved clinical complete response (cCR) and 33 achieved pCR after NACT. Mean Ki-67 index in overall study population, in pCR group and no pCR group was 46.44 ± 22.92%, 51.60 ± 22.3% and 44.06 ± 22.7%, respectively. On univariate analysis, ER negativity, PR negativity and Her 2neu positivity were found predictive of pCR. On subgroup analysis, TNBC and Her 2neu positive sub groups were associated with higher cCR and pCR rate. We found no significant association between Ki-67 and pCR. This result may be confounded by the fact that a significant duration of the study was in the COVID-19 pandemic. Validation of this data is required in a large prospective study.
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Affiliation(s)
- Sukruti Dave
- Department of Medical Oncology, Apollo Hospitals International Limited: Apollo Hospitals Ahmedabad, Ahmedabad, Gujarat India
| | - Arpan Choudhury
- Department of Surgical Oncology, Apollo Hospitals International Limited: Apollo Hospitals Ahmedabad, Ahmedabad, Gujarat India
| | - Shirish S. Alurkar
- Department of Medical Oncology, Apollo Hospitals International Limited: Apollo Hospitals Ahmedabad, Ahmedabad, Gujarat India
| | - Akash M. Shah
- Department of Medical Oncology, Apollo Hospitals International Limited: Apollo Hospitals Ahmedabad, Ahmedabad, Gujarat India
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3
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Petrelli F, Tomasello G, Parati MC, Ghidini A, Ghidini M, Borgonovo K, Cabiddu M, Ghilardi M, Reduzzi R, Gambini D, Zaniboni A, Faustinelli G, Garrone O. Different Chemotherapy Regimens and Pathologic Complete Response in Triple-Negative Breast Cancer: An Updated Network Meta-Analysis of Phase 3 Trials. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:341. [PMID: 38399628 PMCID: PMC10890456 DOI: 10.3390/medicina60020341] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 02/04/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024]
Abstract
Background and Objectives: Currently, the standard treatment for non-metastatic triple-negative breast cancer (TNBC) consists of a systemic neoadjuvant (or perioperative) anthracycline plus taxane-based chemotherapy, delivered either sequentially or concomitantly. We performed a network meta-analysis (NMA) to compare the relative efficacy of different neoadjuvant treatments for TNBC in terms of pathologic complete response (pCR). Materials and Methods: The MEDLINE, Embase, and Cochrane databases were searched from database inception to 1 November 2023. Randomized clinical trials were used that enrolled adults with stage I-III TNBC and provided data on pCR defined as residual ypT0/TisN0M0. Between-group comparisons were estimated using risk ratios (RRs) with 95% credible intervals (95% CrIs). The primary outcome was the pCR rate. Results: 1129 citations were screened, and 12 randomized clinical trials were included. In Bayesian comparisons, all regimens, except anthracycline/taxanes plus gemcitabine or capecitabine, resulted in a higher pCR than the standard regimen in both direct and indirect comparisons. In particular, immunotherapy-based regimens resulted in more than double the pCR compared to historical regimens (RR = 2.3, 95% CI 1.9-2.9) and ranked as being the optimal regimen with a probability of 97%. Disease-free survival was better for immune checkpoint inhibitor-based chemotherapy (HR = 0.36, 95% 1.21-2.09) than for historical regimens. Conclusion: This meta-analysis confirmed that incorporating immunotherapy with neoadjuvant platinum-based chemotherapy is the best option to guarantee remarkable pathologic downstaging and improve clinical outcomes.
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Affiliation(s)
- Fausto Petrelli
- Oncology Unit, ASST Bergamo Ovest, 24047 Treviglio, Italy; (F.P.); (M.C.P.); (K.B.)
| | - Gianluca Tomasello
- Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy (O.G.)
| | - Maria Chiara Parati
- Oncology Unit, ASST Bergamo Ovest, 24047 Treviglio, Italy; (F.P.); (M.C.P.); (K.B.)
| | | | - Michele Ghidini
- Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy (O.G.)
| | - Karen Borgonovo
- Oncology Unit, ASST Bergamo Ovest, 24047 Treviglio, Italy; (F.P.); (M.C.P.); (K.B.)
| | - Mary Cabiddu
- ASP IMMEeS & PAT, 20146 Milano, Italy; (M.C.); (G.F.)
| | - Mara Ghilardi
- Oncology Unit, ASST Bergamo Ovest, 24047 Treviglio, Italy; (F.P.); (M.C.P.); (K.B.)
| | | | - Donatella Gambini
- Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy (O.G.)
| | | | | | - Ornella Garrone
- Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy (O.G.)
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Donati B, Reggiani F, Torricelli F, Santandrea G, Rossi T, Bisagni A, Gasparini E, Neri A, Cortesi L, Ferrari G, Bisagni G, Ragazzi M, Ciarrocchi A. Spatial Distribution of Immune Cells Drives Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer. Cancer Immunol Res 2024; 12:120-134. [PMID: 37856875 DOI: 10.1158/2326-6066.cir-23-0076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 06/22/2023] [Accepted: 10/19/2023] [Indexed: 10/21/2023]
Abstract
Neoadjuvant chemotherapy (NAC) alone or combined with target therapies represents the standard of care for localized triple-negative breast cancer (TNBC). However, only a fraction of patients have a response, necessitating better understanding of the complex elements in the TNBC ecosystem that establish continuous and multidimensional interactions. Resolving such complexity requires new spatially-defined approaches. Here, we used spatial transcriptomics to investigate the multidimensional organization of TNBC at diagnosis and explore the contribution of each cell component to response to NAC. Starting from a consecutive retrospective series of TNBC cases, we designed a case-control study including 24 patients with TNBC of which 12 experienced a pathologic complete response (pCR) and 12 no-response or progression (pNR) after NAC. Over 200 regions of interest (ROI) were profiled. Our computational approaches described a model that recapitulates clinical response to therapy. The data were validated in an independent cohort of patients. Differences in the transcriptional program were detected in the tumor, stroma, and immune infiltrate comparing patients with a pCR with those with pNR. In pCR, spatial contamination between the tumor mass and the infiltrating lymphocytes was observed, sustained by a massive activation of IFN-signaling. Conversely, pNR lesions displayed increased pro-angiogenetic signaling and oxygen-based metabolism. Only modest differences were observed in the stroma, revealing a topology-based functional heterogeneity of the immune infiltrate. Thus, spatial transcriptomics provides fundamental information on the multidimensionality of TNBC and allows an effective prediction of tumor behavior. These results open new perspectives for the improvement and personalization of therapeutic approaches to TNBCs.
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Affiliation(s)
- Benedetta Donati
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Francesca Reggiani
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Federica Torricelli
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Giacomo Santandrea
- Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Teresa Rossi
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Alessandra Bisagni
- Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Elisa Gasparini
- Oncology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Antonino Neri
- Scientific Directorate, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Laura Cortesi
- Department of Oncology and Hematology, Azienda Ospedaliera Policlinico di Modena, Modena, Italy
| | - Guglielmo Ferrari
- Breast Surgery Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Giancarlo Bisagni
- Oncology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Moira Ragazzi
- Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
- Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Alessia Ciarrocchi
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
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Al Husban H, Al Rabadi A, Odeh AH, Abu Rumman K, Alkhawaldeh F, Noures H, Abo Ashoor M, Abu Rumman A, Atmeh M, Bawaneh M. Clinical Characteristics and Management of Triple-Negative Breast Cancer (TNBC) in Jordan: A Retrospective Analysis. Cureus 2024; 16:e53053. [PMID: 38410339 PMCID: PMC10896140 DOI: 10.7759/cureus.53053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2024] [Indexed: 02/28/2024] Open
Abstract
Introduction Triple-negative breast cancer (TNBC) is known for its aggressive nature and poor prognosis. Despite its responsiveness to chemotherapy, TNBC presents challenges in terms of survival, recurrence, and mortality rates, particularly in diverse populations. Limited research in the Middle East hampers comprehensive understanding and tailored management. Methods A retrospective study at the King Hussein Medical Center in Jordan between the period 2009 to 2023 explored TNBC patients (n=110) who underwent adjuvant chemotherapy after local excision or modified radical mastectomy (MRM). Data encompassed demographics, clinical variables, and operative details. Statistical analysis employed Wilcoxon and chi-squared tests, examining mortality risks and associations between variables. Results Among 110 TNBC patients (mean age 52), 84% underwent MRM, 16% wide local excision and axillary clearance (WLE&AC). Lymphovascular invasion (LVI) was observed in 41%, linked to higher lymph node positivity. Neoadjuvant therapy preceded MRM in 25% of cases. While 75% had grade III tumors, the prevalence of invasive ductal carcinoma was 85%. Conclusions This study contributes crucial insights into TNBC characteristics and management in Jordan. Despite limitations such as retrospective design and sample size, the findings underscore the need for tailored interventions in TNBC patients, emphasizing the importance of neoadjuvant therapy and vigilant consideration of LVI status in treatment planning. Future longitudinal research should delve into disease progression and treatment outcomes in diverse populations, facilitating optimized TNBC management strategies.
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Affiliation(s)
- Hussein Al Husban
- Department of General Surgery, Jordanian Royal Medical Services, Amman, JOR
| | - Anas Al Rabadi
- Department of General Surgery, Jordanian Royal Medical Services, Amman, JOR
| | - Ala H Odeh
- Department of General Surgery, Jordanian Royal Medical Services, Amman, JOR
| | - Kahled Abu Rumman
- Department of General Surgery, Jordanian Royal Medical Services, Amman, JOR
| | - Feras Alkhawaldeh
- Department of General Surgery, Jordanian Royal Medical Services, Amman, JOR
| | - Haneen Noures
- Department of Pathology, Jordanian Royal Medical Services, Amman, JOR
| | - Mohammad Abo Ashoor
- Department of Clinical Oncology, Jordanian Royal Medical Services, Amman, JOR
| | - Anas Abu Rumman
- Department of General Surgery, Jordanian Royal Medical Services, Amman, JOR
| | - Mousa Atmeh
- Department of Clinical Oncology, Jordanian Royal Medical Services, Amman, JOR
| | - Mohannad Bawaneh
- Department of General Surgery, Jordanian Royal Medical Services, Amman, JOR
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Saleh GA, Batouty NM, Gamal A, Elnakib A, Hamdy O, Sharafeldeen A, Mahmoud A, Ghazal M, Yousaf J, Alhalabi M, AbouEleneen A, Tolba AE, Elmougy S, Contractor S, El-Baz A. Impact of Imaging Biomarkers and AI on Breast Cancer Management: A Brief Review. Cancers (Basel) 2023; 15:5216. [PMID: 37958390 PMCID: PMC10650187 DOI: 10.3390/cancers15215216] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 10/13/2023] [Accepted: 10/21/2023] [Indexed: 11/15/2023] Open
Abstract
Breast cancer stands out as the most frequently identified malignancy, ranking as the fifth leading cause of global cancer-related deaths. The American College of Radiology (ACR) introduced the Breast Imaging Reporting and Data System (BI-RADS) as a standard terminology facilitating communication between radiologists and clinicians; however, an update is now imperative to encompass the latest imaging modalities developed subsequent to the 5th edition of BI-RADS. Within this review article, we provide a concise history of BI-RADS, delve into advanced mammography techniques, ultrasonography (US), magnetic resonance imaging (MRI), PET/CT images, and microwave breast imaging, and subsequently furnish comprehensive, updated insights into Molecular Breast Imaging (MBI), diagnostic imaging biomarkers, and the assessment of treatment responses. This endeavor aims to enhance radiologists' proficiency in catering to the personalized needs of breast cancer patients. Lastly, we explore the augmented benefits of artificial intelligence (AI), machine learning (ML), and deep learning (DL) applications in segmenting, detecting, and diagnosing breast cancer, as well as the early prediction of the response of tumors to neoadjuvant chemotherapy (NAC). By assimilating state-of-the-art computer algorithms capable of deciphering intricate imaging data and aiding radiologists in rendering precise and effective diagnoses, AI has profoundly revolutionized the landscape of breast cancer radiology. Its vast potential holds the promise of bolstering radiologists' capabilities and ameliorating patient outcomes in the realm of breast cancer management.
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Affiliation(s)
- Gehad A. Saleh
- Diagnostic and Interventional Radiology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; (G.A.S.)
| | - Nihal M. Batouty
- Diagnostic and Interventional Radiology Department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; (G.A.S.)
| | - Abdelrahman Gamal
- Computer Science Department, Faculty of Computers and Information, Mansoura University, Mansoura 35516, Egypt (A.E.T.)
| | - Ahmed Elnakib
- Electrical and Computer Engineering Department, School of Engineering, Penn State Erie, The Behrend College, Erie, PA 16563, USA;
| | - Omar Hamdy
- Surgical Oncology Department, Oncology Centre, Mansoura University, Mansoura 35516, Egypt;
| | - Ahmed Sharafeldeen
- Bioengineering Department, University of Louisville, Louisville, KY 40292, USA
| | - Ali Mahmoud
- Bioengineering Department, University of Louisville, Louisville, KY 40292, USA
| | - Mohammed Ghazal
- Electrical, Computer, and Biomedical Engineering Department, Abu Dhabi University, Abu Dhabi 59911, United Arab Emirates; (M.G.)
| | - Jawad Yousaf
- Electrical, Computer, and Biomedical Engineering Department, Abu Dhabi University, Abu Dhabi 59911, United Arab Emirates; (M.G.)
| | - Marah Alhalabi
- Electrical, Computer, and Biomedical Engineering Department, Abu Dhabi University, Abu Dhabi 59911, United Arab Emirates; (M.G.)
| | - Amal AbouEleneen
- Computer Science Department, Faculty of Computers and Information, Mansoura University, Mansoura 35516, Egypt (A.E.T.)
| | - Ahmed Elsaid Tolba
- Computer Science Department, Faculty of Computers and Information, Mansoura University, Mansoura 35516, Egypt (A.E.T.)
- The Higher Institute of Engineering and Automotive Technology and Energy, New Heliopolis, Cairo 11829, Egypt
| | - Samir Elmougy
- Computer Science Department, Faculty of Computers and Information, Mansoura University, Mansoura 35516, Egypt (A.E.T.)
| | - Sohail Contractor
- Department of Radiology, University of Louisville, Louisville, KY 40202, USA
| | - Ayman El-Baz
- Bioengineering Department, University of Louisville, Louisville, KY 40292, USA
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Wang C, Liu Z, Chen X, Qiao J, Lu Z, Li L, Sun X, Zhang C, Yue X, Xia Q, Zhang H, Yan M. Neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin in early triple-negative breast cancer: a single-arm phase II trial. Nat Commun 2023; 14:6654. [PMID: 37863916 PMCID: PMC10589334 DOI: 10.1038/s41467-023-42479-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Accepted: 10/12/2023] [Indexed: 10/22/2023] Open
Abstract
Immunotherapy combined with chemotherapy has been demonstrated to be effective in early triple-negative breast cancer (TNBC). In this single-arm, phase II study with Simon's two-stage design, we investigated the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy in patients with early TNBC (NCT04213898). Eligible female patients aged 18 years or older with histologically confirmed treatment-naïve early TNBC were treated with camrelizumab (200 mg, on day 1), nab-paclitaxel (125 mg/m2, on days 1, 8, and 15), and epirubicin (75 mg/m2, on day 1) every three weeks for six cycles. The primary end point was the pathological complete response; secondary endpoints included safety, objective response rate, and long-term survival outcomes of event-free survival, disease-free survival, and distant disease-free survival. A total of 39 patients were enrolled between January 2020 and October 2021. Twenty-five patients achieved a pathological complete response (64.1%, 95%CI: 47.2, 78.8). The objective response rate was 89.7% (95%CI: 74.8, 96.7), including 35 patients with partial responses. Treatment-related adverse events of grade 3 or 4 occurred in 30 (76.9%) patients. In conclusion, the trial meets the prespecified endpoints showing promising efficacy and manageable safety of neoadjuvant camrelizumab plus nab-paclitaxel and epirubicin chemotherapy in female patients with early TNBC. Long-term survival outcomes are still pending.
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Affiliation(s)
- Chengzheng Wang
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Zhenzhen Liu
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China.
| | - Xiuchun Chen
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Jianghua Qiao
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Zhenduo Lu
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Lianfang Li
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xianfu Sun
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Chongjian Zhang
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Xiayu Yue
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Qingxin Xia
- Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - He Zhang
- Department of Pathology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
| | - Min Yan
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, China
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Garutti M, Cucciniello L, Arpino G, Fabi A, Livi L, Munzone E, Staropoli N, Zamagni C, Zambelli A, Puglisi F. Risk-Based Therapeutic Strategies for HER2-Positive Early Breast Cancer: A Consensus Paper. Clin Breast Cancer 2023; 23:e458-e469. [PMID: 37543499 DOI: 10.1016/j.clbc.2023.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 07/11/2023] [Accepted: 07/24/2023] [Indexed: 08/07/2023]
Abstract
Breast cancer represents the most commonly diagnosed neoplasm worldwide and the HER2-positive subtype accounts for nearly 1 in 5 breast cancers. The majority of patients with breast cancer present with an early-stage disease upon diagnosis, which is thus susceptible to virtually curative treatment strategies. For a stage, I T1a/b N0 HER2-positive disease, upfront surgery followed by adjuvant therapy is the preferred approach. However, there is some uncertainty regarding the appropriate management of stage cT1c cN0, as both the neoadjuvant approach and upfront surgery have been proven to be feasible therapeutic options. The aim of this Delphi consensus was to define the best strategies for the treatment of early HER2-positive breast cancer. This work may help clinicians in the management of early HER2-positive breast cancer.
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Affiliation(s)
- Mattia Garutti
- CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy.
| | - Linda Cucciniello
- CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; Department of Medicine, University of Udine, Udine, Italy
| | - Grazia Arpino
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Alessandra Fabi
- Precision Medicine in Breast Cancer Unit, Department of Woman and Child Health and Public Health, IRCCS, Scientific Directorate, Fondazione Policlinico Universitario A. Gemelli, Rome, Italy
| | - Lorenzo Livi
- Radiation Oncology Unit, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Elisabetta Munzone
- Division of Medical Senology, European Institute of Oncology, IRCCS, Milan, Italy
| | - Nicoletta Staropoli
- Medical Oncology and Translational Medical Oncology Units, Department of Experimental and Clinical Medicine, Magna Graecia University, AOU Materdomini Catanzaro, Campus Salvatore Venuta, Catanzaro, Italy
| | - Claudio Zamagni
- Medical Oncology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Alberto Zambelli
- Department of Biomedical Sciences Humanitas University and IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy
| | - Fabio Puglisi
- CRO Aviano, National Cancer Institute, IRCCS, Aviano, Italy; Department of Medicine, University of Udine, Udine, Italy
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9
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Zhao F, Shen G, Dong Q, Xin Y, Huo X, Wang M, Liu Z, Zhao Y, Ren D, Xie Q, Liu Z, Li Z, Gao L, Du F, Zhao J. Impact of platinum-based chemotherapy on the prognosis of early triple-negative breast cancer: a systematic review and meta-analysis. Clin Exp Med 2023; 23:2025-2040. [PMID: 36422737 DOI: 10.1007/s10238-022-00940-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 11/02/2022] [Indexed: 11/25/2022]
Abstract
Although platinum-based chemotherapy can improve pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC), the impact on survival of platinum-based neoadjuvant and adjuvant chemotherapy is still controversial. Our meta-analysis aimed at analyzing survival with platinum-based neoadjuvant and adjuvant chemotherapy in patients with TNBC. We searched PubMed, EMBASE, MEDLINE, Cochrane databases, and several major conferences up to January 2021. Fixed and random models were used for our meta-analysis. Disease-free survival (DFS), overall survival (OS), and side effects data were extracted from the included literature in addition to the corresponding pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). A total of nine studies involving 3247 patients were included. The pooled analysis suggested that compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy could further improve DFS (HR = 0.56, 95% CI 0.45-0.67, p < 0.01) and OS (HR = 0.54, 95% CI 0.38-0.70, p < 0.01) in patients with TNBC. The subgroup analysis showed that platinum-based chemotherapy could further improve DFS (HR = 0.59, 95% CI 0.43-0.74, p < 0.01) and OS (HR = 0.61, 95% CI 0.40-0.83, p < 0.01) in neoadjuvant chemotherapy and DFS (HR = 0.53, 95% CI 0.37-0.69, p < 0.01) and OS (HR = 0.46, 95% CI 0.23-0.69, p < 0.01) in adjuvant chemotherapy compared with anthracycline- and/or paclitaxel-based chemotherapy in patients with TNBC. In addition, compared with anthracycline-based chemotherapy, platinum-based chemotherapy without anthracycline chemotherapy could further improve DFS (HR = 0.53, 95% CI 0.37-0.70, p < 0.01) and OS (HR = 0.46, 95%CI 0.19-0.72, p < 0.01) in patients with TNBC. Compared with anthracycline- and/or paclitaxel-based chemotherapy, all-grade diarrhea, fatigue, and grade ≥ 3 anemia were higher in platinum-based chemotherapy. In contrast, all-grade anemia, leukopenia, neutropenia, peripheral neuropathy, myalgia/arthralgia, cardiac toxicity were lower in platinum-based chemotherapy; grade ≥ 3 leukopenia, neutropenia and myalgia/arthralgia were also lower. Compared with anthracycline- and/or paclitaxel-based chemotherapy, platinum-based chemotherapy was more associated with improved DFS and OS in TNBC patients. The benefit of survival is consistent with platinum-based neoadjuvant and adjuvant chemotherapy. The side effects of platinum-based chemotherapy are tolerable.
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Affiliation(s)
- Fuxing Zhao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Guoshuang Shen
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Qiuxia Dong
- The Fifth People's Hospital of Qinghai Province, The First Ward of Oncology, Xining, 810000, China
| | - Yuanfang Xin
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Xingfa Huo
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Miaozhou Wang
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Zhen Liu
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Yi Zhao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Dengfeng Ren
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Qiqi Xie
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Zhilin Liu
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Zitao Li
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Lihong Gao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China
| | - Feng Du
- Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing), The VIPII Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Jiuda Zhao
- Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China.
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10
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El Hejjioui B, Lamrabet S, Amrani Joutei S, Senhaji N, Bouhafa T, Malhouf MA, Bennis S, Bouguenouch L. New Biomarkers and Treatment Advances in Triple-Negative Breast Cancer. Diagnostics (Basel) 2023; 13:diagnostics13111949. [PMID: 37296801 DOI: 10.3390/diagnostics13111949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 03/22/2023] [Accepted: 03/24/2023] [Indexed: 06/12/2023] Open
Abstract
Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer lacking hormone receptor expression and HER2 gene amplification. TNBC represents a heterogeneous subtype of breast cancer, characterized by poor prognosis, high invasiveness, high metastatic potential, and a tendency to relapse. In this review, the specific molecular subtypes and pathological aspects of triple-negative breast cancer are illustrated, with particular attention to the biomarker characteristics of TNBC, namely: regulators of cell proliferation and migration and angiogenesis, apoptosis-regulating proteins, regulators of DNA damage response, immune checkpoints, and epigenetic modifications. This paper also focuses on omics approaches to exploring TNBC, such as genomics to identify cancer-specific mutations, epigenomics to identify altered epigenetic landscapes in cancer cells, and transcriptomics to explore differential mRNA and protein expression. Moreover, updated neoadjuvant treatments for TNBC are also mentioned, underlining the role of immunotherapy and novel and targeted agents in the treatment of TNBC.
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Affiliation(s)
- Brahim El Hejjioui
- Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30050, Morocco
- Department of Medical Genetics and Oncogenetics, HASSAN II University Hospital, Fez 30050, Morocco
| | - Salma Lamrabet
- Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30050, Morocco
| | - Sarah Amrani Joutei
- Department of Radiotherapy, HASSAN II University Hospital, Fez 30050, Morocco
| | - Nadia Senhaji
- Faculty of Sciences, Moulay Ismail University, Meknès 50000, Morocco
| | - Touria Bouhafa
- Department of Radiotherapy, HASSAN II University Hospital, Fez 30050, Morocco
| | | | - Sanae Bennis
- Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez 30050, Morocco
| | - Laila Bouguenouch
- Department of Medical Genetics and Oncogenetics, HASSAN II University Hospital, Fez 30050, Morocco
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11
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Zhu Z, Shen H, Xu J, Fang Z, Wo G, Ma Y, Yang K, Wang Y, Yu Q, Tang JH. GATA3 mediates doxorubicin resistance by inhibiting CYB5R2-catalyzed iron reduction in breast cancer cells. Drug Resist Updat 2023; 69:100974. [PMID: 37230023 DOI: 10.1016/j.drup.2023.100974] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 04/26/2023] [Accepted: 05/04/2023] [Indexed: 05/27/2023]
Abstract
AIMS Neoadjuvant chemotherapy (NAC) is the primary preoperative therapy for breast cancer. The luminal subtype of breast cancer shows less NAC response than the basal subtype, with an inefficient NAC treatment effect. Understanding of the molecular and cellular mechanisms responsible for this chemoresistance is an important issue when determining optimal treatment. METHODS Doxorubicin-induced apoptosis and ferroptosis was investigated using cytotoxicity, western blotting, and flow cytometry assays. The role of GATA3 in modulating doxorubicin-induced cell death was investigated both in vitro and in vivo. RNA-seq, qPCR, ChIP, and luciferase assay and association analyses were performed to investigate the regulation of CYB5R2 by GATA3. The function of GATA3 and CYB5R2 in regulating doxorubicin-induced ferroptosis was evaluated with iron, ROS, and lipid peroxidation detection assays. Immunohistochemistry was performed for results validation. RESULTS Doxorubicin-induced basal breast cancer cell death is dependent on iron-mediated ferroptosis. Overexpression of the luminal signature transcriptional factor GATA3 mediates doxorubicin resistance. GATA3 promotes cell viability by decreasing ferroptosis-related gene CYB5R2 expression and by maintaining iron homeostasis. Analyzing data from the public and our cohorts demonstrates that GATA3 and CYB5R2 are associated with NAC response. CONCLUSIONS GATA3 promotes doxorubicin resistance by inhibiting CYB5R2-mediated iron metabolism and ferroptosis. Therefore, patients with breast cancer who display high GATA3 expression do not benefit from doxorubicin-based NAC regimens.
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Affiliation(s)
- Zhen Zhu
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
| | - Hongyu Shen
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China; Gusu School, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215026, PR China
| | - Jialin Xu
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China
| | - Zheng Fang
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China
| | - Guanqun Wo
- Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Ying Ma
- Foreign Language Teaching Department, Nanjing University of Chinese Medicine, Nanjing 210023, PR China
| | - Kai Yang
- The People's Hospital of Pizhou, Xuzhou 221300, PR China
| | - Yalin Wang
- First Clinical Medical College, Xuzhou Medical University, Xuzhou 221004, PR China
| | - Qiang Yu
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
| | - Jin-Hai Tang
- Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China; Gusu School, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215026, PR China.
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12
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Bhardwaj PV, Mason H, Kaufman SA, Visintainer P, Makari-Judson G. Outcomes of a Multidisciplinary Team in the Management of Patients with Early-Stage Breast Cancer Undergoing Neoadjuvant Chemotherapy at a Community Cancer Center. Curr Oncol 2023; 30:4861-4870. [PMID: 37232824 PMCID: PMC10217230 DOI: 10.3390/curroncol30050366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 03/31/2023] [Accepted: 05/04/2023] [Indexed: 05/27/2023] Open
Abstract
Background: The utilization of neoadjuvant chemotherapy (NAC) remains highly variable in clinical practice. The implementation of NAC requires coordination of handoffs between a multidisciplinary team (MDT). This study aims to assess the outcomes of an MDT in the management of early-stage breast cancer patients undergoing neoadjuvant chemotherapy at a community cancer center. Methods: We conducted a retrospective case series on patients receiving NAC for early-stage operable or locally advanced breast cancer coordinated by an MDT. Outcomes of interest included the rate of downstaging of cancer in the breast and axilla, time from biopsy to NAC, time from completion of NAC to surgery, and time from surgery to radiation therapy (RT). Results: Ninety-four patients underwent NAC; 84% were White and mean age was 56.5 yrs. Of them, 87 (92.5%) had clinical stage II or III cancer, and 43 (45.8%) had positive lymph nodes. Thirty-nine patients (42.9%) were triple negative, 28 (30.8%) were human epidermal growth factor receptor (HER-2)+, and 24 (26.2%) were estrogen receptor (ER) +HER-2-. Of 91 patients, 23 (25.3%) achieved pCR; 84 patients (91.4%) had downstaging of the breast tumor, and 30 (33%) had axillary downstaging. The median time from diagnosis to NAC was 37.5 days, the time from completion of NAC to surgery was 29 days, and the time from surgery to RT was 49.5 days. Conclusions: Our MDT provided timely, coordinated, and consistent care for patients with early-stage breast cancer undergoing NAC as evidenced by time to treatment outcomes consistent with recommended national trends.
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Affiliation(s)
- Prarthna V. Bhardwaj
- Division of Hematology—Oncology, University of Massachusetts Chan Medical School—Baystate, 759 Chestnut Street, Springfield, MA 01199 , USA
| | - Holly Mason
- Breast Surgery Section, University of Massachusetts Chan Medical School—Baystate, 759 Chestnut Street, Springfield, MA 01199, USA
| | - Seth A. Kaufman
- Division of Radiation Oncology, University of Massachusetts Chan Medical School—Baystate, 759 Chestnut Street, Springfield, MA 01199, USA
| | - Paul Visintainer
- Institute for Healthcare Delivery and Population Science, University of Massachusetts Chan Medical—Baystate, 759 Chestnut Street, Springfield, MA 01199, USA
| | - Grace Makari-Judson
- Division of Hematology—Oncology, University of Massachusetts Chan Medical School—Baystate, 759 Chestnut Street, Springfield, MA 01199 , USA
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13
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Huober J, van Mackelenbergh M, Schneeweiss A, Seither F, Blohmer JU, Denkert C, Tesch H, Hanusch C, Salat C, Rhiem K, Solbach C, Fasching PA, Jackisch C, Reinisch M, Lederer B, Mehta K, Link T, Nekljudova V, Loibl S, Untch M. Identifying breast cancer patients at risk of relapse despite pathological complete response after neoadjuvant therapy. NPJ Breast Cancer 2023; 9:23. [PMID: 37029138 PMCID: PMC10082019 DOI: 10.1038/s41523-023-00525-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 03/13/2023] [Indexed: 04/09/2023] Open
Abstract
This retrospective pooled analysis aims to identify factors predicting relapse despite a pathologic complete response (pCR) in patients with breast cancer (BC). 2066 patients with a pCR from five neoadjuvant GBG/AGO-B trials fulfill the inclusion criteria of this analysis. Primary endpoint is disease-free survival (DFS); secondary endpoints is distant DFS (DDFS) and overall survival (OS). After a median follow-up of 57.6 months, DFS is significantly worse for patients with positive lymph nodes (cN+ vs cN0 hazard ratio [HR] 1.94, 95%CI 1.48-2.54; p < 0.001). In patients with triple-negative tumors, lobular histology (lobular vs other HR 3.55, 95%CI 1.53-8.23; p = 0.003), and clinical nodal involvement (cN+ vs cN0 HR 2.45, 95%CI 1.59-3.79; p < 0.001) predict a higher risk of DFS events. Patients with HER2-positive cT3/4 tumors have a significantly higher risk of relapse (cT3/4 vs cT1 HR 2.07, 95%CI 1.06-4.03; p = 0.033). Initial tumor load and histological type predict relapse in patients with a pCR.
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Affiliation(s)
- Jens Huober
- Universitätsfrauenklinik Ulm, Brustzentrum, Germany
- Kantonsspital St.Gallen, Brustzentrum, Departement Interdisziplinäre medizinische Dienste, St. Gallen, Switzerland
| | - Marion van Mackelenbergh
- Brustzentrum, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Arnold-Heller-Straße 3, 24105, Kiel, Germany.
| | | | | | - Jens-Uwe Blohmer
- Gynäkologie mit Brustzentrum, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Carsten Denkert
- Institut für Pathologie, Philipps-Universität Marburg, Marburg, Germany
| | - Hans Tesch
- Centrum für Hämatologie und Onkologie Bethanien Frankfurt, Frankfurt, Germany
| | | | - Christoph Salat
- Hämatologisch-Onkologische Schwerpunktpraxis Salat/Stötzer, München, Germany
| | - Kerstin Rhiem
- Zentrum Familiärer Brust- und Eierstockkrebs, Uniklinik Köln, Germany
| | | | | | | | | | | | | | - Theresa Link
- Department of Gynecology and Obstetrics, Technische Universität Dresden, Dresden, Germany
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14
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Zapperi S, La Porta CAM. The Response of Triple-Negative Breast Cancer to Neoadjuvant Chemotherapy and the Epithelial–Mesenchymal Transition. Int J Mol Sci 2023; 24:ijms24076422. [PMID: 37047393 PMCID: PMC10094549 DOI: 10.3390/ijms24076422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/25/2023] [Accepted: 03/28/2023] [Indexed: 04/03/2023] Open
Abstract
It would be highly desirable to find prognostic and predictive markers for triple-negative breast cancer (TNBC), a strongly heterogeneous and invasive breast cancer subtype often characterized by a high recurrence rate and a poor outcome. Here, we investigated the prognostic and predictive capabilities of ARIADNE, a recently developed transcriptomic test focusing on the epithelial–mesenchymal transition. We first compared the stratification of TNBC patients obtained by ARIADNE with that based on other common pathological indicators, such as grade, stage and nodal status, and found that ARIADNE was more effective than the other methods in dividing patients into groups with different disease-free survival statistics. Next, we considered the response to neoadjuvant chemotherapy and found that the classification provided by ARIADNE led to statistically significant differences in the rates of pathological complete response within the groups.
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15
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Basmadjian RB, Chow K, Kim D, Kenney M, Lukmanji A, O'Sullivan DE, Xu Y, Quan ML, Cheung WY, Lupichuk S, Brenner DR. The Association between Early-Onset Diagnosis and Clinical Outcomes in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2023; 15:cancers15071923. [PMID: 37046584 PMCID: PMC10093252 DOI: 10.3390/cancers15071923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/16/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Early-onset diagnosis, defined by age <40 years, has historically been associated with inferior outcomes in breast cancer. Recent evidence suggests that this association is modified by molecular subtype. We performed a systematic review and meta-analysis of the literature to synthesize evidence on the association between early-onset diagnosis and clinical outcomes in triple-negative breast cancer (TNBC). Studies comparing the risk of clinical outcomes in non-metastatic TNBC between early-onset patients and later-onset patients (≥40 years) were queried in Medline and EMBASE from inception to February 2023. Separate meta-analyses were performed for breast cancer specific survival (BCSS), overall survival (OS), and disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), and pathological complete response (pCR). In total, 7581 unique records were identified, and 36 studies satisfied inclusion criteria. The pooled risk of any recurrence was significantly greater in early-onset patients compared to later-onset patients. Better BCSS and OS were observed in early-onset patients relative to later-onset patients aged >60 years. The pooled odds of achieving pCR were significantly higher in early-onset patients. Future studies should evaluate the role of locoregional management of TNBC and the implementation of novel therapies such as PARP inhibitors in real-world settings, and whether they improve outcomes.
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Affiliation(s)
- Robert B Basmadjian
- Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
| | - Kristian Chow
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
| | - Dayoung Kim
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
| | - Matthew Kenney
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
| | - Aysha Lukmanji
- Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
| | - Dylan E O'Sullivan
- Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
- Department of Cancer Epidemiology and Prevention Research, Cancer Research & Analytics, Cancer Care Alberta, Alberta Health Services, Calgary, AB T2S 3C3, Canada
| | - Yuan Xu
- Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
- Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
| | - May Lynn Quan
- Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
- Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
| | - Winson Y Cheung
- Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
| | - Sasha Lupichuk
- Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
| | - Darren R Brenner
- Department of Community Health Sciences, Foothills Medical Centre, University of Calgary, Calgary, AB T2N 2T9, Canada
- Department of Oncology, Tom Baker Cancer Centre, University of Calgary, Calgary, AB T2N 4N2, Canada
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16
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Zhu JW, Charkhchi P, Adekunte S, Akbari MR. What Is Known about Breast Cancer in Young Women? Cancers (Basel) 2023; 15:cancers15061917. [PMID: 36980802 PMCID: PMC10047861 DOI: 10.3390/cancers15061917] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 03/17/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
Breast cancer (BC) is the second leading cause of cancer-related death in women under the age of 40 years worldwide. In addition, the incidence of breast cancer in young women (BCYW) has been rising. Young women are not the focus of screening programs and BC in younger women tends to be diagnosed in more advanced stages. Such patients have worse clinical outcomes and treatment complications compared to older patients. BCYW has been associated with distinct tumour biology that confers a worse prognosis, including poor tumour differentiation, increased Ki-67 expression, and more hormone-receptor negative tumours compared to women >50 years of age. Pathogenic variants in cancer predisposition genes such as BRCA1/2 are more common in early-onset BC compared to late-onset BC. Despite all these differences, BCYW remains poorly understood with a gap in research regarding the risk factors, diagnosis, prognosis, and treatment. Age-specific clinical characteristics or outcomes data for young women are lacking, and most of the standard treatments used in this subpopulation currently are derived from older patients. More age-specific clinical data and treatment options are required. In this review, we discuss the epidemiology, clinicopathologic characteristics, outcomes, treatments, and special considerations of breast cancer in young women. We also underline future directions and highlight areas that require more attention in future studies.
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Affiliation(s)
- Jie Wei Zhu
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
- Department of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Parsa Charkhchi
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
| | - Shadia Adekunte
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
| | - Mohammad R Akbari
- Women's College Research Institute, Women's College Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada
- Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
- Dalla Lana School of Public Health, University of Toronto, Toronto, ON M5T 3M7, Canada
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17
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Das C, Adhikari S, Bhattacharya A, Chakraborty S, Mondal P, Yadav SS, Adhikary S, Hunt CR, Yadav K, Pandita S, Roy S, Tainer JA, Ahmed Z, Pandita TK. Epigenetic-Metabolic Interplay in the DNA Damage Response and Therapeutic Resistance of Breast Cancer. Cancer Res 2023; 83:657-666. [PMID: 36661847 PMCID: PMC11285093 DOI: 10.1158/0008-5472.can-22-3015] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/30/2022] [Accepted: 01/04/2023] [Indexed: 01/21/2023]
Abstract
Therapy resistance is imposing a daunting challenge on effective clinical management of breast cancer. Although the development of resistance to drugs is multifaceted, reprogramming of energy metabolism pathways is emerging as a central but heterogenous regulator of this therapeutic challenge. Metabolic heterogeneity in cancer cells is intricately associated with alterations of different signaling networks and activation of DNA damage response pathways. Here we consider how the dynamic metabolic milieu of cancer cells regulates their DNA damage repair ability to ultimately contribute to development of therapy resistance. Diverse epigenetic regulators are crucial in remodeling the metabolic landscape of cancer. This epigenetic-metabolic interplay profoundly affects genomic stability of the cancer cells as well as their resistance to genotoxic therapies. These observations identify defining mechanisms of cancer epigenetics-metabolism-DNA repair axis that can be critical for devising novel, targeted therapeutic approaches that could sensitize cancer cells to conventional treatment strategies.
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Affiliation(s)
- Chandrima Das
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
- Homi Bhaba National Institute, Mumbai 400094, India
| | - Swagata Adhikari
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
- Homi Bhaba National Institute, Mumbai 400094, India
| | - Apoorva Bhattacharya
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
| | | | - Payel Mondal
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
- Homi Bhaba National Institute, Mumbai 400094, India
| | - Shalini S. Yadav
- The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Santanu Adhikary
- Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India
- Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata, India
| | - Clayton R Hunt
- Houston Methodist Research Institute, Houston, TX, 77030, USA
| | - Kamlesh Yadav
- Center for Genomics and Precision Medicine, Texas A&M College of Medicine, Houston, Texas, 77030, USA
| | - Shruti Pandita
- University of Texas Health San Antonio MD Anderson Cancer Center, San Antonio, Texas, 78229, USA
| | - Siddhartha Roy
- Structural Biology and Bioinformatics Division, Council of Scientific and Industrial Research (CSIR)-Indian Institute of Chemical Biology, Kolkata, India
| | - John A Tainer
- The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Zamal Ahmed
- The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Tej K. Pandita
- Houston Methodist Research Institute, Houston, TX, 77030, USA
- Center for Genomics and Precision Medicine, Texas A&M College of Medicine, Houston, Texas, 77030, USA
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18
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Eckardt NK, Ignatov A, Meinecke AM, Burger E, Costa SD, Eggemann H. Tumor characteristics, therapy, and prognosis in young breast cancer patients ≤ 35 years. J Cancer Res Clin Oncol 2023; 149:709-719. [PMID: 36534272 DOI: 10.1007/s00432-022-04374-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 09/18/2022] [Indexed: 12/23/2022]
Abstract
PURPOSES Young breast cancer patients aged 35 years and younger are a small group of women who tend to present at high-risk form of the disease. More analysis of the data on tumor characteristics, treatment, and survival is necessary to help improving treatment and outcome. METHODS In this retrospective study, we compared the clinical and tumor characteristics, the treatments, and the survival of 257 women aged ≤ 35 years, with 6566 women aged 50-69 years. We used a registry-based data of patients with invasive, non-metastatic breast cancer diagnosed between 2000 and 2015. RESULTS Young women showed lower rate of hormone receptor (HR) positivity. Their tumors were more often HER2-positive, which showed lower rate of differentiation and higher rate of Ki-67 expression compared to their older counterparts. Women aged 35 years and younger were more likely to undergo neoadjuvant therapy and mastectomy. Endocrine therapy was underrepresented in young patients. 5-Year disease-free survival (DFS) was significantly lower in the younger patient group (81.7% vs. 91.3%, p < 0.001), while 5-year overall survival (OS) was not impaired (91.4% vs. 91.1%, p = 0.847). CONCLUSION The unfavorable disease-free survival in the group of younger patients might be explained by their unfavorable tumor characteristics. The surgical treatment appears to be more aggressive in young breast cancer patients and is more frequently combined with chemotherapy and immunotherapy, either in a neoadjuvant or in an adjuvant setting.
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Affiliation(s)
- Naaja-Kristin Eckardt
- Department of Gynecology and Obstetrics, Otto-Von-Guericke University, Magdeburg, Germany
| | - Atanas Ignatov
- Department of Gynecology and Obstetrics, Otto-Von-Guericke University, Magdeburg, Germany
- Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany
| | - Anne-Marie Meinecke
- Department of Gynecology and Obstetrics, Otto-Von-Guericke University, Magdeburg, Germany
| | - Elke Burger
- Cancer Registry Magdeburg, Magdeburg, Germany
| | - Serban-Dan Costa
- Department of Gynecology and Obstetrics, Otto-Von-Guericke University, Magdeburg, Germany
| | - Holm Eggemann
- Department of Gynecology and Obstetrics, Otto-Von-Guericke University, Magdeburg, Germany.
- Department of Gynecology and Obstetrics, Klinikum Magdeburg gGmbH, Mageburg, Germany.
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19
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Şeber ES, İriagac Y, Çavdar E, Karaboyun K, Avcı O, Yolcu A, Gürdal SÖ, Öznur M. A logarithmic model for hormone receptor-positive and breast cancer patients treated with neoadjuvant chemotherapy. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2023; 69:434-439. [PMID: 36921198 PMCID: PMC10004284 DOI: 10.1590/1806-9282.20221255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 12/20/2022] [Indexed: 03/12/2023]
Abstract
OBJECTIVE The aim of this study was to investigate the predictive importance of the previously validated log(ER)*log(PgR)/Ki-67 predictive model in a larger patient population. METHODS Patients with hormone receptor positive/HER-2 negative and clinical node positive before chemotherapy were included. Log(ER)*log(PgR)/Ki-67 values of the patients were determined, and the ideal cutoff value was calculated using a receiver operating characteristic curve analysis. It was analyzed with a logistic regression model along with other clinical and pathological characteristics. RESULTS A total of 181 patients were included in the study. The ideal cutoff value for pathological response was 0.12 (area under the curve=0.585, p=0.032). In the univariate analysis, no statistical correlation was observed between luminal subtype (p=0.294), histological type (p=0.238), clinical t-stage (p=0.927), progesterone receptor level (p=0.261), Ki-67 cutoff value (p=0.425), and pathological complete response. There was a positive relationship between numerical increase in age and residual disease. As the grade of the patients increased, the probability of residual disease decreased. Patients with log(ER)*log(PgR)/Ki-67 above 0.12 had an approximately threefold increased risk of residual disease when compared to patients with 0.12 and below (odds ratio: 3.17, 95% confidence interval: 1.48-6.75, p=0.003). When age, grade, and logarithmic formula were assessed together, the logarithmic formula maintained its statistical significance (odds ratio: 2.47, 95% confidence interval: 1.07-5.69, p=0.034). CONCLUSION In hormone receptor-positive breast cancer patients receiving neoadjuvant chemotherapy, the logarithmic model has been shown in a larger patient population to be an inexpensive, easy, and rapidly applicable predictive marker that can be used to predict response.
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Affiliation(s)
- Erdoğan Selçuk Şeber
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Medical Oncology - Tekirdag, Turkey
| | - Yakup İriagac
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Medical Oncology - Tekirdag, Turkey
| | - Eyyup Çavdar
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Medical Oncology - Tekirdag, Turkey
| | - Kubilay Karaboyun
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Medical Oncology - Tekirdag, Turkey
| | - Okan Avcı
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Medical Oncology - Tekirdag, Turkey
| | - Ahmet Yolcu
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Radiation Oncology - Tekirdag, Turkey
| | - Sibel Özkan Gürdal
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Surgical Oncology - Tekirdag, Turkey
| | - Meltem Öznur
- Tekirdağ Namık Kemal University, Faculty of Medicine, Department of Pathology - Tekirdag, Turkey
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20
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Li Y, Chen H, He J, Fan Z, Zhang H. The outcome of neoadjuvant chemotherapy and the current trend of surgical treatment in young women with breast cancer: A multicenter real-world study (CSBrS-012). Front Public Health 2023; 11:1100421. [PMID: 36895689 PMCID: PMC9988895 DOI: 10.3389/fpubh.2023.1100421] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 02/01/2023] [Indexed: 02/23/2023] Open
Abstract
Background and objectives The relationship between age and the outcome of breast cancer neoadjuvant chemotherapy (NAC) remains controversial, and little is known about the choice of surgical treatment for young patients. In this multicenter real-world study, we sought to analyze the outcome of NAC as well as the current status and trend of surgical decision-making after NAC in young breast cancer patients. Methods The medical records of patients from 20 hospitals in different regions of China were collected retrospectively. The study population included females diagnosed with cT1-4N0-3M0 breast cancer who received NAC from January 2010 to December 2020. Results A total of 9,643 eligible patients were included, 1,945 (20.2%) of whom were ≤40 years old. Young patients tend to have a higher tumor stage and a higher proportion of Luminal B and triple-negative breast cancer (TNBC) tumors compared with the >40-year-old group. The breast pathological complete response (pCR) rate in the young group was 20.3%, and Luminal B tumor was more likely to obtain pCR in young patients. The implementation rate of breast-conserving surgery (BCS) and breast reconstruction surgery was higher in young patients and tended to increase over time. In different regions of China, there were great differences in the choice of surgical treatment after NAC among young patients. Conclusion Breast cancer in young women has unique clinical characteristics, but age does not affect the overall pCR rate. In China, the BCS rate after NAC is increasing over time but is still at a low level.
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Affiliation(s)
- Yijun Li
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Heyan Chen
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jianjun He
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Zhimin Fan
- Department of Breast Surgery, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Huimin Zhang
- Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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21
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Yu Y, Zhang J, Lin Y, Kang S, Lv X, Song C. Efficacy and safety of neoadjuvant therapy for triple-negative breast cancer: a Bayesian network meta-analysis. Expert Rev Anticancer Ther 2022; 22:1141-1151. [DOI: 10.1080/14737140.2022.2125381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Affiliation(s)
- Yushuai Yu
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
| | - Jie Zhang
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
- Breast Cancer Institute, Fujian Medical University, Fuzhou 350001, Fujian Province, China
| | - Yuxiang Lin
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
- Breast Cancer Institute, Fujian Medical University, Fuzhou 350001, Fujian Province, China
| | - Shaohong Kang
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
| | - Xinyin Lv
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
| | - Chuangui Song
- Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
- Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, 350001, China
- Breast Cancer Institute, Fujian Medical University, Fuzhou 350001, Fujian Province, China
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22
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Ribeiro R, Carvalho MJ, Goncalves J, Moreira JN. Immunotherapy in triple-negative breast cancer: Insights into tumor immune landscape and therapeutic opportunities. Front Mol Biosci 2022; 9:903065. [PMID: 36060249 PMCID: PMC9437219 DOI: 10.3389/fmolb.2022.903065] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 07/13/2022] [Indexed: 12/24/2022] Open
Abstract
Triple-negative breast cancer (TNBC) is a clinically aggressive subtype of breast cancer that represents 15-20% of breast tumors and is more prevalent in young pre-menopausal women. It is the subtype of breast cancers with the highest metastatic potential and recurrence at the first 5 years after diagnosis. In addition, mortality increases when a complete pathological response is not achieved. As TNBC cells lack estrogen, progesterone, and HER2 receptors, patients do not respond well to hormone and anti-HER2 therapies, and conventional chemotherapy remains the standard treatment. Despite efforts to develop targeted therapies, this disease continues to have a high unmet medical need, and there is an urgent demand for customized diagnosis and therapeutics. As immunotherapy is changing the paradigm of anticancer treatment, it arises as an alternative treatment for TNBC patients. TNBC is classified as an immunogenic subtype of breast cancer due to its high levels of tumor mutational burden and presence of immune cell infiltrates. This review addresses the implications of these characteristics for the diagnosis, treatment, and prognosis of the disease. Herein, the role of immune gene signatures and tumor-infiltrating lymphocytes as biomarkers in TNBC is reviewed, identifying their application in patient diagnosis and stratification, as well as predictors of efficacy. The expression of PD-L1 expression is already considered to be predictive of response to checkpoint inhibitor therapy, but the challenges regarding its value as biomarker are described. Moreover, the rationales for different formats of immunotherapy against TNBC currently under clinical research are discussed, and major clinical trials are highlighted. Immune checkpoint inhibitors have demonstrated clinical benefit, particularly in early-stage tumors and when administered in combination with chemotherapy, with several regimens approved by the regulatory authorities. The success of antibody-drug conjugates and research on other emerging approaches, such as vaccines and cell therapies, will also be addressed. These advances give hope on the development of personalized, more effective, and safe treatments, which will improve the survival and quality of life of patients with TNBC.
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Affiliation(s)
- Rita Ribeiro
- CNC—Center for Neurosciences and Cell Biology, Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Faculty of Medicine (Polo 1), Coimbra, Portugal
- iMed.ULisboa—Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
- Univ Coimbra—University of Coimbra, CIBB, Faculty of Pharmacy, Coimbra, Portugal
| | - Maria João Carvalho
- Univ Coimbra—University of Coimbra, CIBB, Faculty of Pharmacy, Coimbra, Portugal
- CHUC—Coimbra Hospital and University Centre, Department of Gynaecology, Coimbra, Portugal
- Univ Coimbra—University Clinic of Gynaecology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- iCBR—Institute for Clinical and Biomedical Research Area of Environment Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- CACC—Clinical Academic Center of Coimbra, Coimbra, Portugal
| | - João Goncalves
- iMed.ULisboa—Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
| | - João Nuno Moreira
- CNC—Center for Neurosciences and Cell Biology, Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Faculty of Medicine (Polo 1), Coimbra, Portugal
- Univ Coimbra—University of Coimbra, CIBB, Faculty of Pharmacy, Coimbra, Portugal
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23
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Irajizad E, Wu R, Vykoukal J, Murage E, Spencer R, Dennison JB, Moulder S, Ravenberg E, Lim B, Litton J, Tripathym D, Valero V, Damodaran S, Rauch GM, Adrada B, Candelaria R, White JB, Brewster A, Arun B, Long JP, Do KA, Hanash S, Fahrmann JF. Application of Artificial Intelligence to Plasma Metabolomics Profiles to Predict Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer. Front Artif Intell 2022; 5:876100. [PMID: 36034598 PMCID: PMC9403735 DOI: 10.3389/frai.2022.876100] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 05/03/2022] [Indexed: 11/13/2022] Open
Abstract
There is a need to identify biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are less likely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied artificial intelligence to comprehensive metabolic profiles to identify additional metabolites associated with treatment response. Using a deep learning model (DLM), a metabolite panel consisting of two polyamines as well as nine additional metabolites was developed for improved prediction of RCB-II/III. The DLM has potential clinical value for identifying TNBC patients who are unlikely to respond to NACT and who may benefit from other treatment modalities.
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Affiliation(s)
- Ehsan Irajizad
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Ranran Wu
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jody Vykoukal
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Eunice Murage
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Rachelle Spencer
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jennifer B. Dennison
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Stacy Moulder
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Elizabeth Ravenberg
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Bora Lim
- Breast Cancer Research Program, Baylor College of Medicine, Houston, TX, United States
| | - Jennifer Litton
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Debu Tripathym
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Vicente Valero
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Senthil Damodaran
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Gaiane M. Rauch
- Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Beatriz Adrada
- Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Rosalind Candelaria
- Department of Breast Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Jason B. White
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Abenaa Brewster
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Banu Arun
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - James P. Long
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Kim Anh Do
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Sam Hanash
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- *Correspondence: Sam Hanash
| | - Johannes F. Fahrmann
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
- Johannes F. Fahrmann
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24
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Matsuda M, Fukuyama N, Matsuda T, Kikuchi S, Shiraishi Y, Takimoto Y, Kamei Y, Kurata M, Kitazawa R, Kido T. Utility of synthetic MRI in predicting pathological complete response of various breast cancer subtypes prior to neoadjuvant chemotherapy. Clin Radiol 2022; 77:855-863. [DOI: 10.1016/j.crad.2022.06.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Revised: 06/24/2022] [Accepted: 06/27/2022] [Indexed: 11/25/2022]
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25
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Katayama A, Starczynski J, Toss MS, Shaaban AM, Provenzano E, Quinn CM, Callagy G, Purdie CA, Millican-Slater R, Purnell D, Chagla L, Oyama T, Pinder SE, Chan S, Ellis I, Lee AHS, Rakha EA. The frequency and clinical significance of centromere enumeration probe 17 alterations in HER2 immunohistochemistry-equivocal invasive breast cancer. Histopathology 2022; 81:511-519. [PMID: 35879836 PMCID: PMC9545957 DOI: 10.1111/his.14728] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 07/14/2022] [Accepted: 07/21/2022] [Indexed: 11/30/2022]
Abstract
Background and aims Chromosome 17 alterations affect the assessment of HER2 gene amplification in breast cancer (BC), but its clinical significance remains unclear. This study aimed to identify the prevalence of centromere enumeration probe 17 (CEP17) alterations, and its correlation with response to neoadjuvant therapy (NAT) in BC patients with human epidermal growth factor receptor 2 (HER2) immunohistochemistry‐equivocal score. Methods and results A large BC cohort (n = 6049) with HER2 immunohistochemistry score 2+ and florescent in‐situ hybridisation (FISH) results was included to assess the prevalence of CEP17 alterations. Another cohort (n = 885) with available clinicopathological data was used to evaluate the effect of CEP17 in the setting of NAT. HER2‐amplified tumours with monosomy 17 (CEP17 copy number < 1.5 per nucleus), normal 17 (CEP17 1.5–< 3.0) and polysomy 17 (CEP17 ≥ 3.0) were observed in 16, 59 and 25%, respectively, compared with 3, 74 and 23%, respectively, in HER2‐non‐amplified tumours. There was no significant relationship between CEP17 alterations and pathological complete response (pCR) rate in both HER2‐amplified and HER2‐non‐amplified tumours. The independent predictors of pCR were oestrogen (ER) negativity in HER2‐amplified tumours [ER negative versus positive; odds ratio (OR) = 11.80; 95% confidence interval (CI) = 1.37–102.00; P = 0.02], and histological grade 3 in HER2 non‐amplified tumours (3 versus 1, 2; OR = 5.54; 95% CI = 1.61–19.00; P = 0.007). Conclusion The impacts of CEP17 alterations are not as strong as those of HER2/CEP17 ratio and HER2 copy number. The hormonal receptors status and tumour histological grade are more useful to identify BC patients with a HER2 immunohistochemistry‐equivocal score who would benefit from NAT.
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Affiliation(s)
- Ayaka Katayama
- Translational Medical Sciences Unit, School of Medicine, University of Nottingham, Nottingham, UK.,Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Jane Starczynski
- Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Edgebaston, Birmingham, UK
| | - Michael S Toss
- Translational Medical Sciences Unit, School of Medicine, University of Nottingham, Nottingham, UK
| | - Abeer M Shaaban
- Department of Cellular Pathology, University Hospitals Birmingham NHS Foundation Trust, Edgebaston, Birmingham, UK.,Institute of Cancer and Genomic Sciences, The University of Birmingham, Edgebaston, Birmingham, UK
| | - Elena Provenzano
- Department of Histopathology, Cambridge University NHS Foundation Trust, Cambridge, UK
| | - Cecily M Quinn
- Department of Histopathology, St. Vincent's University Hospital, Dublin, and School of Medicine, University College Dublin, Ireland
| | - Grace Callagy
- Discipline of Pathology, School of Medicine, Lambe Institute for Translational Research, NUI, Galway, Ireland
| | - Colin A Purdie
- Department of Breast Pathology, Ninewells Hospital and Medical School, Dundee, UK
| | | | - David Purnell
- Histopathology department, University Hospitals of Leicester, Leicester, UK
| | - Leena Chagla
- Burney Breast Unit , St Helens and Knowsley Teaching Hospital NHS Trust, UK
| | - Tetsunari Oyama
- Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Japan
| | - Sarah E Pinder
- Division of Cancer Studies, King's College London, Guy's Hospital, London, UK
| | - Steve Chan
- Department of Oncology, Nottingham University Hospitals NHS Trust, Nottingham, UK
| | - Ian Ellis
- Translational Medical Sciences Unit, School of Medicine, University of Nottingham, Nottingham, UK.,Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham, City Hospital Nottingham, UK
| | - Andrew H S Lee
- Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham, City Hospital Nottingham, UK
| | - Emad A Rakha
- Translational Medical Sciences Unit, School of Medicine, University of Nottingham, Nottingham, UK.,Department of Histopathology, Nottingham University Hospitals NHS Trust, Nottingham, City Hospital Nottingham, UK
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26
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Domergue C, Martin E, Lemarié C, Jézéquel P, Frenel JS, Augereau P, Campone M, Patsouris A. Impact of HER2 Status on Pathological Response after Neoadjuvant Chemotherapy in Early Triple-Negative Breast Cancer. Cancers (Basel) 2022; 14:2509. [PMID: 35626113 PMCID: PMC9139240 DOI: 10.3390/cancers14102509] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/10/2022] [Accepted: 05/13/2022] [Indexed: 02/06/2023] Open
Abstract
PURPOSE Investigates the link between HER2 status and histological response after neoadjuvant chemotherapy in patients with early TNBC. METHODS We retrieved clinical and anatomopathological data retrospectively from 449 patients treated for the first time with standard neoadjuvant chemotherapy for early unilateral BC between 2005 and 2020. The primary endpoint was pathological complete response (pCR, i.e., ypT0 ypN0), according to HER2 status. Secondary endpoints included invasive disease-free survival (I-DFS) and overall survival (OS). RESULTS 437 patients were included, and 121 (27.7%) patients had HER2-low tumours. The pCR rate was not significantly different between the HER2-low group vs. the HER2-0 group (35.7% versus 41.8%, p = 0.284) in either univariate analysis or multivariate analysis adjusted for TNM classification and grade (odds ratio [OR] = 0.70, confidence interval [CI] 95% 0.45-1.08). With a median follow-up of 72.9 months, no significant survival differences were observed between patients with HER2-low tumours vs. patients with HER2-0 tumours in terms of I-DFS (p = 0.487) and OS (p = 0.329). CONCLUSIONS In our cohort, HER2 status was not significantly associated with pCR in a manner consistent with data published recently on TNBC. However, the prognostic impact of HER2-low expression among TNBC patients warrants further evaluation.
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Affiliation(s)
- Camille Domergue
- Medical Oncology Department, ICO Institut de Cancérologie de l’Ouest, 49000 Angers, France; (P.A.); (M.C.); (A.P.)
| | - Elodie Martin
- Clinical Trial Sponsor Unit/Biometry, ICO Institut de Cancérologie de l’Ouest, 44800 Saint-Herblain, France;
| | - Camille Lemarié
- Biopathology Department, ICO Institut de Cancérologie de l’Ouest, 44800 Saint-Herblain, France;
| | - Pascal Jézéquel
- Omics Data Science Unit, ICO Institut de Cancérologie de l’Ouest, 44800 Saint-Herblain, France;
| | - Jean-Sebastien Frenel
- Medical Oncology Department, ICO Institut de Cancérologie de l’Ouest, 44800 Saint-Herblain, France;
| | - Paule Augereau
- Medical Oncology Department, ICO Institut de Cancérologie de l’Ouest, 49000 Angers, France; (P.A.); (M.C.); (A.P.)
| | - Mario Campone
- Medical Oncology Department, ICO Institut de Cancérologie de l’Ouest, 49000 Angers, France; (P.A.); (M.C.); (A.P.)
| | - Anne Patsouris
- Medical Oncology Department, ICO Institut de Cancérologie de l’Ouest, 49000 Angers, France; (P.A.); (M.C.); (A.P.)
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O6-Methylguanine-DNA Methyltransferase and ATP-Binding Cassette Membrane Transporter G2 Promotor Methylation: Can Predict the Response to Chemotherapy in Advanced Breast Cancer? Rep Biochem Mol Biol 2022; 11:20-29. [PMID: 35765521 PMCID: PMC9208568 DOI: 10.52547/rbmb.11.1.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 11/02/2021] [Indexed: 01/11/2023]
Abstract
Background ATP-binding cassette membrane transporter G2 (ABCG2) gene is one of transporter family and well characterized for their association with chemoresistance. Promoter methylation is a mechanism for regulation of gene expression. O6-Methyl guanine DNA methyl transferase (MGMT) gene plays a fundamental role in DNA repair. MGMT has the ability to remove alkyl adducts from DNA at the O6 position of guanine. Alkylating agents exert their function through adding these alkyls adducts to DNA leading to cell death unless it is repaired by MGMT. MGMT promoter was found to be methylated in several malignancies. The aim of the present work is to study the relation of MGMT and ABCG2 promoter methylation status in advanced breast cancer patients to response to cyclophosphamide-doxorubicin (AC) based therapeutic regime. Methods This retrospective study included Forty-two female patients with advanced breast cancer assessed before receiving chemotherapy and after the completion of regimens. They were grouped into responders and non-responders according to RECIST criteria. Methylation analysis of MGMT and ABCG2 genes were performed on breast cancer tissues. Results MGMT promoter was methylated in 40.5% of the cases. ABCG2 promoter was methylated in 14.3% of cases. There was no statistically significant association between MGMT and ABCG2 promoter methylation status and clinicopathological parameters. There was statistically significant association between methylation status of both promoters and response to AC when followed by Taxane. Conclusion Methylation of MGMT and ABCG2 promoters combined could be a potential predictive factor for response to cyclophosphamide-doxorubicin based therapeutic regime.
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Takada K, Kashiwagi S, Asano Y, Goto W, Morisaki T, Shibutani M, Tanaka H, Hirakawa K, Ohira M. Differences in tumor-infiltrating lymphocyte density and prognostic factors for breast cancer by patient age. World J Surg Oncol 2022; 20:38. [PMID: 35177074 PMCID: PMC8851811 DOI: 10.1186/s12957-022-02513-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 02/07/2022] [Indexed: 11/10/2022] Open
Abstract
Background Lymphocytes that surround cancer participate in tumor-related immune responses and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs index the tumor microenvironment and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TIL density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of preoperative chemotherapy (POC) in BC patients who were aged either less than 45 years or more than 60 years. Methods We retrospectively examined the data of 356 breast cancer patients who underwent POC, including 75 patients aged ≤ 45 years and 116 patients aged > 60 years. Using pre-treatment needle biopsy specimens, TIL density was compared for each age group by Student’s t-test. After analyzing different factors that affect TIL density, prognostic factors were also examined. Results Older patients with triple-negative BC had significantly lower TIL density than younger patients, while in human epidermal growth factor receptor 2 (HER2)-enriched BC, TIL density was significantly higher in the younger age group than that in the older age group. In addition, younger patients with HER2-rich breast cancer showed significantly higher complete pathological response rates than older patients with HER2-rich BC. In addition, significant differences in overall survival were observed among these patients with triple-negative BC. Conclusions Our study suggests that younger BC patients possess significantly higher TIL density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-022-02513-5.
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Affiliation(s)
- Koji Takada
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Shinichiro Kashiwagi
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
| | - Yuka Asano
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Wataru Goto
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Tamami Morisaki
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Masatsune Shibutani
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Hiroaki Tanaka
- Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Kosei Hirakawa
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.,Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Masaichi Ohira
- Department of Breast and Endocrine Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.,Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
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Chen LJ, Chang YJ, Chang YJ. Treatment and long-term outcome of breast cancer in very young women: nationwide population-based study. BJS Open 2021; 5:6406857. [PMID: 34672342 PMCID: PMC8529521 DOI: 10.1093/bjsopen/zrab087] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 08/03/2021] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND The study aimed to assess the correlation between long-term survival and treatment in very young women with breast cancer. METHODS Data on women with breast cancer were retrieved from the Taiwan Cancer Registry between 2004 and 2014. Patients who did not undergo surgery or who had stage 0 or IV disease were excluded. Survival analysis was conducted. The participants were divided into very young (20-29.9 years), young (30-39.9 years), and adult (40-50.0 years) groups. RESULTS Among 104 115 women, 24 474 (572 very young, 5565 young, and 18 337 adult) were eligible for the study. Median follow-up was 79.5 (range 24-158) months. The mortality rates in the very young, young, and adult groups were 12.9, 10.0, and 8.2 per cent respectively (P < 0.001). Very young patients had higher histological grade, unfavourable subtype, higher TNM stage, and received more breast-conserving surgery (BCS). Kaplan-Meier survival analysis showed that very young patients had the poorest long-term survival. Very young patients with stage II disease had the worst prognosis. In the multivariable regression model, radiotherapy was associated with decreased local recurrence but not with improved overall, cancer-specific, or disease-free survival for stage II disease in the very young group. Surgery type and chemotherapy were not associated with significant improvement in overall survival. CONCLUSION Very young patients with stage II disease had poor long-term outcomes. BCS had no detrimental effects on long-term outcomes.
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Affiliation(s)
- L-J Chen
- Department of Surgery, HepingFuyou Branch, Taipei City Hospital, Taipei, Taiwan.,Department of Surgery, University of Taipei, Taipei, Taiwan
| | - Y-J Chang
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.,Department of Surgery, Zhong-Xing Branch, Taipei City Hospital, Taipei, Taiwan
| | - Y-J Chang
- Department of Surgery, Taipei Tzu Chi Hospital, New Taipei City, Taiwan.,Department of Surgery, School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan
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30
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Oner G, Önder S, Karatay H, Ak N, Tükenmez M, Müslümanoğlu M, İğci A, Dincçağ A, Özmen V, Aydiner A, Yavuz E, Cabioğlu N. Clinical impact of PD-L1 expression in triple-negative breast cancer patients with residual tumor burden after neoadjuvant chemotherapy. World J Surg Oncol 2021; 19:264. [PMID: 34474671 PMCID: PMC8414710 DOI: 10.1186/s12957-021-02361-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 08/05/2021] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival. METHODS PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC). RESULTS Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by "MD Anderson Cancer Center Residual Cancer Burden Index" (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 46.3% and 51.4%, respectively. A high (> 20%) tumoral PD-L1 positivity was associated with a better DFS and DSS. CONCLUSIONS Studies in the literature mostly focused on PD-L1 expression in inflammatory cells. However, our results suggest that patients with a high PD-L1 expression on TCs were more likely to have a better outcome. Since patients with residual tumor burden who express PD-L1 on TILs were more likely to respond to NACT, an immune checkpoint inhibitor therapy in addition to NACT would be an important option for TNBC with locally advanced disease.
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Affiliation(s)
- Gizem Oner
- grid.9601.e0000 0001 2166 6619Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey ,grid.411414.50000 0004 0626 3418Multidisciplinary Oncologic Centre Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium ,grid.5284.b0000 0001 0790 3681Center for Oncological Research (CORE), University of Antwerp, Wilrijk, Belgium
| | - Semen Önder
- grid.9601.e0000 0001 2166 6619Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Hüseyin Karatay
- grid.9601.e0000 0001 2166 6619Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Naziye Ak
- grid.9601.e0000 0001 2166 6619Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey
| | - Mustafa Tükenmez
- grid.9601.e0000 0001 2166 6619Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mahmut Müslümanoğlu
- grid.9601.e0000 0001 2166 6619Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Abdullah İğci
- grid.9601.e0000 0001 2166 6619Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ahmet Dincçağ
- grid.9601.e0000 0001 2166 6619Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Vahit Özmen
- grid.9601.e0000 0001 2166 6619Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Adnan Aydiner
- grid.9601.e0000 0001 2166 6619Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey
| | - Ekrem Yavuz
- grid.9601.e0000 0001 2166 6619Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Neslihan Cabioğlu
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
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31
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In-depth characterization of a new patient-derived xenograft model for metaplastic breast carcinoma to identify viable biologic targets and patterns of matrix evolution within rare tumor types. Clin Transl Oncol 2021; 24:127-144. [PMID: 34370182 PMCID: PMC8732292 DOI: 10.1007/s12094-021-02677-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Accepted: 06/07/2021] [Indexed: 11/24/2022]
Abstract
Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype with rapid growth, high rates of metastasis, recurrence and drug resistance, and diverse molecular and histological heterogeneity. Patient-derived xenografts (PDXs) provide a translational tool and physiologically relevant system to evaluate tumor biology of rare subtypes. Here, we provide an in-depth comprehensive characterization of a new PDX model for MBC, TU-BcX-4IC. TU-BcX-4IC is a clinically aggressive tumor exhibiting rapid growth in vivo, spontaneous metastases, and elevated levels of cell-free DNA and circulating tumor cell DNA. Relative chemosensitivity of primary cells derived from TU-BcX-4IC was performed using the National Cancer Institute (NCI) oncology drug set, crystal violet staining, and cytotoxic live/dead immunofluorescence stains in adherent and organoid culture conditions. We employed novel spheroid/organoid incubation methods (Pu·MA system) to demonstrate that TU-BcX-4IC is resistant to paclitaxel. An innovative physiologically relevant system using human adipose tissue was used to evaluate presence of cancer stem cell-like populations ex vivo. Tissue decellularization, cryogenic-scanning electron microscopy imaging and rheometry revealed consistent matrix architecture and stiffness were consistent despite serial transplantation. Matrix-associated gene pathways were essentially unchanged with serial passages, as determined by qPCR and RNA sequencing, suggesting utility of decellularized PDXs for in vitro screens. We determined type V collagen to be present throughout all serial passage of TU-BcX-4IC tumor, suggesting it is required for tumor maintenance and is a potential viable target for MBC. In this study we introduce an innovative and translational model system to study cell–matrix interactions in rare cancer types using higher passage PDX tissue.
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32
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Yam C, Yen EY, Chang JT, Bassett RL, Alatrash G, Garber H, Huo L, Yang F, Philips AV, Ding QQ, Lim B, Ueno NT, Kannan K, Sun X, Sun B, Parra Cuentas ER, Symmans WF, White JB, Ravenberg E, Seth S, Guerriero JL, Rauch GM, Damodaran S, Litton JK, Wargo JA, Hortobagyi GN, Futreal A, Wistuba II, Sun R, Moulder SL, Mittendorf EA. Immune Phenotype and Response to Neoadjuvant Therapy in Triple-Negative Breast Cancer. Clin Cancer Res 2021; 27:5365-5375. [PMID: 34253579 DOI: 10.1158/1078-0432.ccr-21-0144] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 05/10/2021] [Accepted: 07/07/2021] [Indexed: 11/16/2022]
Abstract
PURPOSE Increasing tumor-infiltrating lymphocytes (TIL) is associated with higher rates of pathologic complete response (pCR) to neoadjuvant therapy (NAT) in patients with triple-negative breast cancer (TNBC). However, the presence of TILs does not consistently predict pCR, therefore, the current study was undertaken to more fully characterize the immune cell response and its association with pCR. EXPERIMENTAL DESIGN We obtained pretreatment core-needle biopsies from 105 patients with stage I-III TNBC enrolled in ARTEMIS (NCT02276443) who received NAT from Oct 22, 2015 through July 24, 2018. The tumor-immune microenvironment was comprehensively profiled by performing T-cell receptor (TCR) sequencing, programmed death-ligand 1 (PD-L1) IHC, multiplex immunofluorescence, and RNA sequencing on pretreatment tumor samples. The primary endpoint was pathologic response to NAT. RESULTS The pCR rate was 40% (42/105). Higher TCR clonality (median = 0.2 vs. 0.1, P = 0.03), PD-L1 positivity (OR: 2.91, P = 0.020), higher CD3+:CD68+ ratio (median = 14.70 vs. 8.20, P = 0.0128), and closer spatial proximity of T cells to tumor cells (median = 19.26 vs. 21.94 μm, P = 0.0169) were associated with pCR. In a multivariable model, closer spatial proximity of T cells to tumor cells and PD-L1 expression enhanced prediction of pCR when considered in conjunction with clinical stage. CONCLUSIONS In patients receiving NAT for TNBC, deep immune profiling through detailed phenotypic characterization and spatial analysis can improve prediction of pCR in patients receiving NAT for TNBC when considered with traditional clinical parameters.
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Affiliation(s)
- Clinton Yam
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Er-Yen Yen
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jeffrey T Chang
- Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, Texas
| | - Roland L Bassett
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Gheath Alatrash
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Haven Garber
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Lei Huo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Fei Yang
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Anne V Philips
- Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Qing-Qing Ding
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Bora Lim
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Naoto T Ueno
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Kasthuri Kannan
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Xiangjie Sun
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Baohua Sun
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Edwin Roger Parra Cuentas
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - William Fraser Symmans
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jason B White
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Elizabeth Ravenberg
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Sahil Seth
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jennifer L Guerriero
- Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.,Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts
| | - Gaiane M Rauch
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Senthil Damodaran
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jennifer K Litton
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jennifer A Wargo
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Gabriel N Hortobagyi
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Andrew Futreal
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ignacio I Wistuba
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ryan Sun
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Stacy L Moulder
- Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Elizabeth A Mittendorf
- Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts. .,Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts.,Ludwig Center at Harvard, Boston, Massachusetts
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Falcone V, Reiser E, Grula L, Bago-Horvath Z, Stolz M, Catic A, Deutschmann C, Singer C, Pfeiler G. Correlation Between Preoperative Radiological and Postoperative Pathological Tumor Size in Patients With HER2 + Breast Cancer After Neoadjuvant Chemotherapy Plus Trastuzumab and Pertuzumab. Clin Breast Cancer 2021; 22:149-160. [PMID: 34229944 DOI: 10.1016/j.clbc.2021.05.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 05/29/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) in combination with anti-HER2 treatment is standard of care in patients with early HER2 positive breast cancer. Preoperative radiological evaluation is mandatory for defining the extent of surgery. In this study, we evaluated the correlation between preoperative radiological and postoperative pathological tumor size in early HER2 positive patients after neoadjuvant chemotherapy in combination with trastuzumab and pertuzumab. In a patient population with HER2 positive breast cancer, who received neoadjuvant chemotherapy and anti-HER2 treatment, the correlation between preoperative radiological and postoperative pathological tumor size was performed. Concordance of radiological and pathological tumor size was found in 55.7%, leading to more extensive breast surgery as required in 7 cases and to the underestimation of 6 neoplastic lesions before surgery, respectively. PATIENTS AND METHODS Seventy early HER2 positive breast cancer patients were included and retrospectively analysed. All preoperative radiological assessments as well as the tumor board decision on surgical extent and pathological evaluation were completed at the Medical University of Vienna. Preoperative radiological assessment of tumor size and lymph node status were compared with final histopathological findings. The correlation between different radiological modalities regarding tumor size was investigated. RESULTS Concordance of radiological and pathological tumor size was found in 55.7 % (50% by sonography and 66.7% by MRI, respectively) of patients with a nonsignificant correlation of r = 0.31 (P = .08). Of the 39 patients with pathologic complete remission (pCR), 16 were also classified as radiological complete response (rCR) while 23 of those showed a radiological stable disease or partial response. In 6 patients, radiological assessment showed a CR but invasive cancer with a tumor size range from 7 to 36 mm was found in histopathological examination. Neither menopausal status (P= .69) nor BMI (P = .60) and age (P = .50) had an impact on the correlation between radiological and histopathological tumor size. Regarding lymph node status, a statistically significant association and clinically relevant correlation between radiological and histopathological evaluation was found (r = 0.66, P < .001). CONCLUSION Concordance between radiology and histopathology was low regarding tumor size after NAC in combination with trastuzumab and pertuzumab, but significant regarding lymph node status.
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Affiliation(s)
- Veronica Falcone
- Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Austria
| | - Elisabeth Reiser
- Department of Obstetrics and Gynecology, Division of Gynecological Endocrinology and Reproductive medicine, Medical University of Innsbruck, Austria
| | - Lenka Grula
- Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Austria
| | - Zsuzsanna Bago-Horvath
- Department of Pathology, Division of Gynecopathology and Senology, Medical University of Vienna, Austria
| | - Myriam Stolz
- Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Austria
| | - Anja Catic
- Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Austria
| | - Christine Deutschmann
- Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Austria
| | - Christian Singer
- Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Austria
| | - Georg Pfeiler
- Department of Obstetrics and Gynecology, Division of General Gynecology and Gynecologic Oncology, Medical University of Vienna, Austria.
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Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev 2021; 5:CD011220. [PMID: 34037241 PMCID: PMC8150746 DOI: 10.1002/14651858.cd011220.pub2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Retrospective analyses suggest that capecitabine may carry superior activity in hormone receptor-positive relative to hormone receptor-negative metastatic breast cancer. This review examined the veracity of that finding and explored whether this differential activity extends to early breast cancer. OBJECTIVES To assess effects of chemotherapy regimens containing capecitabine compared with regimens not containing capecitabine for women with hormone receptor-positive versus hormone receptor-negative breast cancer across the three major treatment scenarios: neoadjuvant, adjuvant, metastatic. SEARCH METHODS On 4 June 2019, we searched the Cochrane Breast Cancer Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5) in the Cochrane Library; MEDLINE; Embase; the World Health Organization International Clinical Trials Registry Platform; and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials looking at chemotherapy regimens containing capecitabine alone or in combination with other agents versus a control or similar regimen without capecitabine for treatment of breast cancer at any stage. The primary outcome measure for metastatic and adjuvant trials was overall survival (OS), and for neoadjuvant studies pathological complete response (pCR). DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and odds ratios (ORs) for dichotomous outcomes, and meta-analysis was performed using a fixed-effect model. MAIN RESULTS We included 26 studies with outcome data by hormone receptor: 12 metastatic studies (n = 4325), 6 neoadjuvant trials (n = 3152), and 8 adjuvant studies (n = 13,457). Capecitabine treatment was added in several different ways across studies. These could be classified as capecitabine alone compared to another treatment, capecitabine substituted for part of the control chemotherapy, and capecitabine added to control chemotherapy. In the metastatic setting, the effect of capecitabine was heterogenous between hormone receptor-positive and -negative tumours. For OS, no difference between capecitabine-containing and non-capecitabine-containing regimens was observed for all participants taken together (HR 1.01, 95% confidence interval (CI) 0.98 to 1.05; 12 studies, 4325 participants; high-certainty evidence), for those with hormone receptor-positive disease (HR 0.93, 95% CI 0.84 to 1.04; 7 studies, 1834 participants; high-certainty evidence), and for those with hormone receptor-negative disease (HR 1.00, 95% CI 0.88 to 1.13; 8 studies, 1577 participants; high-certainty evidence). For progression-free survival (PFS), a small improvement was seen for all people (HR 0.89, 95% CI 0.82 to 0.96; 12 studies, 4325 participants; moderate-certainty evidence). This was largely accounted for by a moderate improvement in PFS for inclusion of capecitabine in hormone receptor-positive cancers (HR 0.82, 95% CI 0.73 to 0.91; 7 studies, 1594 participants; moderate-certainty evidence) compared to no difference in PFS for hormone receptor-negative cancers (HR 0.96, 95% CI 0.83 to 1.10; 7 studies, 1122 participants; moderate-certainty evidence). Quality of life was assessed in five studies; in general there did not seem to be differences in global health scores between the two treatment groups at around two years' follow-up. Neoadjuvant studies were highly variable in design, having been undertaken to test various experimental regimens using pathological complete response (pCR) as a surrogate for disease-free survival (DFS) and OS. Across all patients, capecitabine-containing regimens resulted in little difference in pCR in comparison to non-capecitabine-containing regimens (odds ratio (OR) 1.12, 95% CI 0.94 to 1.33; 6 studies, 3152 participants; high-certainty evidence). By subtype, no difference in pCR was observed for either hormone receptor-positive (OR 1.22, 95% CI 0.76 to 1.95; 4 studies, 964 participants; moderate-certainty evidence) or hormone receptor-negative tumours (OR 1.28, 95% CI 0.61 to 2.66; 4 studies, 646 participants; moderate-certainty evidence). Four studies with 2460 people reported longer-term outcomes: these investigators detected no difference in either DFS (HR 1.02, 95% CI 0.86 to 1.21; high-certainty evidence) or OS (HR 0.97, 95% CI 0.77 to 1.23; high-certainty evidence). In the adjuvant setting, a modest improvement in OS was observed across all participants (HR 0.89, 95% CI 0.81 to 0.98; 8 studies, 13,547 participants; moderate-certainty evidence), and no difference in OS was seen in hormone receptor-positive cancers (HR 0.86, 95% CI 0.68 to 1.09; 3 studies, 3683 participants), whereas OS improved in hormone receptor-negative cancers (HR 0.72, 95% CI 0.59 to 0.89; 5 studies, 3432 participants). No difference in DFS or relapse-free survival (RFS) was observed across all participants (HR 0.93, 95% CI 0.86 to 1.01; 8 studies, 13,457 participants; moderate-certainty evidence). As was observed for OS, no difference in DFS/RFS was seen in hormone receptor-positive cancers (HR 1.03, 95% CI 0.91 to 1.17; 5 studies, 5604 participants; moderate-certainty evidence), and improvements in DFS/RFS with inclusion of capecitabine were observed for hormone receptor-negative cancers (HR 0.74, 95% CI 0.64 to 0.86; 7 studies, 3307 participants; moderate-certainty evidence). Adverse effects were reported across all three scenarios. When grade 3 or 4 febrile neutropenia was considered, no difference was seen for capecitabine compared to non-capecitabine regimens in neoadjuvant studies (OR 1.31, 95% CI 0.97 to 1.77; 4 studies, 2890 participants; moderate-certainty evidence), and a marked reduction was seen for capecitabine in adjuvant studies (OR 0.55, 95% CI 0.47 to 0.64; 5 studies, 8086 participants; moderate-certainty evidence). There was an increase in diarrhoea and hand-foot syndrome in neoadjuvant (diarrhoea: OR 1.95, 95% CI 1.32 to 2.89; 3 studies, 2686 participants; hand-foot syndrome: OR 6.77, 95% CI 4.89 to 9.38; 5 studies, 3021 participants; both moderate-certainty evidence) and adjuvant trials (diarrhoea: OR 2.46, 95% CI 2.01 to 3.01; hand-foot syndrome: OR 13.60, 95% CI 10.65 to 17.37; 8 studies, 11,207 participants; moderate-certainty evidence for both outcomes). AUTHORS' CONCLUSIONS In summary, a moderate PFS benefit by including capecitabine was seen only in hormone receptor-positive cancers in metastatic studies. No benefit of capecitabine for pCR was noted overall or in hormone receptor subgroups when included in neoadjuvant therapy. In contrast, the addition of capecitabine in the adjuvant setting led to improved outcomes for OS and DFS in hormone receptor-negative cancer. Future studies should stratify by hormone receptor and triple-negative breast cancer (TNBC) status to clarify the differential effects of capecitabine in these subgroups across all treatment scenarios, to optimally guide capecitabine inclusion.
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Affiliation(s)
- Siao-Nge Hoon
- Medical Oncology Department, St John of God Midland, Perth, Australia
- Medical Oncology Department, Sir Charles Gairdner Hospital, Perth, Australia
| | - Peter Kh Lau
- Medical Oncology Department, Sir Charles Gairdner Hospital, Perth, Australia
- Medical Oncology Department, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Alison M White
- Murdoch Community Hospice, St John of God Hospital Murdoch, Perth, Australia
- Palliative Care Department, Royal Perth Hospital, Perth, Australia
| | - Max K Bulsara
- Institute for Health Research, University of Notre Dame Australia, Fremantle, Australia
- School of Population and Global Health, The University of Western Australia, Perth, Australia
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Patricia D Banks
- Medical Oncology Department, Peter MacCallum Cancer Centre, Melbourne, Australia
- Medical Oncology Department, University Hospital Geelong, Geelong, Australia
| | - Andrew D Redfern
- School of Medicine, University of Western Australia, Perth, Australia
- Medical Oncology Department, Fiona Stanley Hospital, Perth, Australia
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Müller C, Schmidt G, Juhasz-Böss I, Jung L, Huwer S, Solomayer EF, Juhasz-Böss S. Influences on pathologic complete response in breast cancer patients after neoadjuvant chemotherapy. Arch Gynecol Obstet 2021; 304:1065-1071. [PMID: 33689016 PMCID: PMC8429372 DOI: 10.1007/s00404-021-06018-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 02/23/2021] [Indexed: 11/30/2022]
Abstract
Purpose Pathologic complete response is associated with longer disease-free survival and better overall survival after neoadjuvant chemotherapy in breast cancer patients. We, therefore, evaluated factors influencing pathologic complete response. Methods Patients receiving neoadjuvant chemotherapy from 2015 to 2018 at the Saarland University Hospital were included. Patients’ age, tumor stage, tumor biology, genetic mutation, recurrent cancer, discontinuation of chemotherapy, and participation in clinical trials were extracted from electronic medical records. Binary logistic regression was performed to evaluate the influence of these factors on pathologic complete response. Results Data of 183 patients were included. The median patient’s age was 54 years (22–78). The median interval between diagnosis and onset of chemotherapy was 28 days (14–91); between end of chemotherapy and surgery 28 days (9–57). Sixty-two patients (34%) participated in clinical trials for chemotherapy. A total of 86 patients (47%) achieved pathologic complete response. Patient’s age, genetic mutation, recurrent cancers, or discontinuation of chemotherapy (due to side effects) and time intervals (between diagnosis and onset of chemotherapy, as well as between end of chemotherapy and surgery) did not influence pathologic complete response. Patients with high Ki67, high grading, Her2 positive tumors, as well as patients participating in clinical trials for chemotherapy had a higher chance of having pathologic complete response. Patients with Luminal B tumors had a lower chance for pathologic complete response. Conclusion Particularly patients with high risk cancer and patients, participating in clinical trials benefit most from chemotherapy. Therefore, breast cancer patients can be encouraged to participate in clinical trials for chemotherapy.
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Affiliation(s)
- Carolin Müller
- Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center, Kirrbergerstraße 100, 66424, Homburg/Saar, Germany.
| | - Gilda Schmidt
- Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center, Kirrbergerstraße 100, 66424, Homburg/Saar, Germany
| | - Ingolf Juhasz-Böss
- Department of Gynecology, Obstetrics and Reproductive Medicine, University Medical Center Freiburg, Freiburg, Germany
| | - Lisa Jung
- Department of Gynecology, Obstetrics and Reproductive Medicine, University Medical Center Freiburg, Freiburg, Germany
| | - Sarah Huwer
- Department of Gynecology, Obstetrics and Reproductive Medicine, University Medical Center Freiburg, Freiburg, Germany
| | - Erich-Franz Solomayer
- Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center, Kirrbergerstraße 100, 66424, Homburg/Saar, Germany
| | - Stephanie Juhasz-Böss
- Department of Gynecology, Obstetrics and Reproductive Medicine, Saarland University Medical Center, Kirrbergerstraße 100, 66424, Homburg/Saar, Germany
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Laas E, Bresset A, Féron JG, Le Gal C, Darrigues L, Coussy F, Grandal B, Laot L, Pierga JY, Reyal F, Hamy AS. HER2-Positive Breast Cancer Patients with Pre-Treatment Axillary Involvement or Postmenopausal Status Benefit from Neoadjuvant Rather than Adjuvant Chemotherapy Plus Trastuzumab Regimens. Cancers (Basel) 2021; 13:370. [PMID: 33498405 PMCID: PMC7864202 DOI: 10.3390/cancers13030370] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/10/2021] [Accepted: 01/16/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND No survival benefit has yet been demonstrated for neoadjuvant chemotherapy (NAC) against HER2-positive tumors in patients with early breast cancer (BC). The objective of this study was to compare the prognosis of HER2-positive BC patients treated with NAC to that of patients treated with adjuvant chemotherapy (AC). MATERIALS AND METHODS We retrospectively analyzed disease-free (DFS) and overall survival (OS) in 202 HER2-positive patients treated with NAC and 701 patients treated with AC. All patients received trastuzumab in addition to chemotherapy. Patient data were weighted by a propensity score to overcome selection bias. RESULTS After inverse probability of treatment weights (IPTW) adjustment, no difference in DFS (p = 0.3) was found between treatments for the total population. However, after multivariate analysis, an interaction was found between cN status and chemotherapy strategy (IPTW-corrected corrected Hazard ratio cHR = 0.52, 95% CI (0.3-0.9), p interaction = 0.08) and between menopausal status and chemotherapy (CT) strategy (cHR = 0.35, 95%CI (0.18-0.7)) p interaction < 0.01). NAC was more beneficial than AC strategy in cN-positive patients and in postmenopausal patients. Moreover, after IPTW adjustment, the multivariate analysis showed that the neoadjuvant strategy conferred a significant OS benefit (cHR = 0.09, 95%CI [0.02-0.35], p < 0.001). CONCLUSION In patients with HER2-positive BC, the NAC strategy is more beneficial than the AC strategy, particularly in cN-positive and postmenopausal patients. NAC should be used as a first-line treatment for HER2-positive tumors.
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Affiliation(s)
- Enora Laas
- Department of Surgery, Institut Curie, 5 rue d’Ulm, 75005 Paris, France; (E.L.); (J.-G.F.); (C.L.G.); (L.L.)
| | - Arnaud Bresset
- Gynecology Department, Beaujon Hospital, 92210 Clichy, France;
| | - Jean-Guillaume Féron
- Department of Surgery, Institut Curie, 5 rue d’Ulm, 75005 Paris, France; (E.L.); (J.-G.F.); (C.L.G.); (L.L.)
| | - Claire Le Gal
- Department of Surgery, Institut Curie, 5 rue d’Ulm, 75005 Paris, France; (E.L.); (J.-G.F.); (C.L.G.); (L.L.)
| | - Lauren Darrigues
- Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, Institut Curie, 75005 Paris, France; (L.D.); (B.G.); (A.-S.H.)
| | - Florence Coussy
- Department of Medical Oncology, Institut Curie, 75005 Paris, France; (F.C.); (J.-Y.P.)
| | - Beatriz Grandal
- Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, Institut Curie, 75005 Paris, France; (L.D.); (B.G.); (A.-S.H.)
| | - Lucie Laot
- Department of Surgery, Institut Curie, 5 rue d’Ulm, 75005 Paris, France; (E.L.); (J.-G.F.); (C.L.G.); (L.L.)
| | - Jean-Yves Pierga
- Department of Medical Oncology, Institut Curie, 75005 Paris, France; (F.C.); (J.-Y.P.)
| | - Fabien Reyal
- Department of Surgery, Institut Curie, 5 rue d’Ulm, 75005 Paris, France; (E.L.); (J.-G.F.); (C.L.G.); (L.L.)
- Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, Institut Curie, 75005 Paris, France; (L.D.); (B.G.); (A.-S.H.)
| | - Anne-Sophie Hamy
- Residual Tumor & Response to Treatment Laboratory, RT2Lab, Translational Research Department, INSERM, U932 Immunity and Cancer, Institut Curie, 75005 Paris, France; (L.D.); (B.G.); (A.-S.H.)
- Department of Medical Oncology, Institut Curie, 75005 Paris, France; (F.C.); (J.-Y.P.)
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Firouzabadi D, Dehghanian A, Rezvani A, Mahmoudi L, Talei A. Addition of carboplatin-gemcitabine as second-line neoadjuvant chemotherapy in non-responsive locally advanced breast cancer patients to standard neoadjuvant chemotherapy and evaluation of factors affecting response: a randomized controlled trial. BMC Cancer 2021; 21:47. [PMID: 33430808 PMCID: PMC7798240 DOI: 10.1186/s12885-020-07652-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 11/17/2020] [Indexed: 12/20/2022] Open
Abstract
Background Neoadjuvant chemotherapy (NACT) is the prime approach to the management of locally advanced breast cancer (LABC). Influenced by different factors such as pathologic tumor characteristics, hormone receptor status, HER2 and proliferation marker expressions, response to therapy cannot be easily predicted. Pathologic complete response (pCR) has been considered as an endpoint to NACT; however, pCR rates have been unsatisfactory in such patients. In this randomized trial, we studied the efficacy of carboplatin/gemcitabine as second-line NACT while evaluating the impact of different factors affecting response. Methods In this randomized controlled trial, 52 clinically non-responsive (confirmed by palpation and/or ultrasonography) LABC patients to 4 cycles of doxorubicin/cyclophosphamide followed by 4 cycles of paclitaxel ± trastuzumab were randomly allocated to two groups. “Control” group underwent breast surgery and were further evaluated for pCR (ypT0/is ypN0). “Intervention” group received 2 cycles of carboplatin/gemcitabine and patients were further evaluated for pCR following surgery. Results In a total of 52 patients, pCR rate was 30.7%. pCR and response rate in lymph nodes were higher in carboplatin/gemcitabine recipients (32% vs 29.7 and 44% vs 40.7% respectively), however differences were insignificant. In both the “intervention” group and total study population, most pCR cases were of the hormone receptor (HR)+/HER2+ subtype (87.5% and 75% respectively). HER2 positivity, ki67 expression, lower extent of ER positivity, higher tumor grade and tumor-infiltrating lymphocyte (TIL) lead to higher pCR rates. Adverse events following addition of carboplatin/gemcitabine were mostly hematologic and none required hospitalization. Anemia was the most common grade 3 adverse event observed. No grade 4 toxicity was evident. Conclusion Although the proposed carboplatin/gemcitabine combination could not improve pCR rates as expected, probability of immune activation following use of carboplatin in achieving response to NACT may be considered. Accounting for the highest number of pCR cases in the “intervention” group, the HR+/HER2+ subtype with high TILs may be considered as most responsive to the proposed regimen in this study. It is noteworthy that the proposed combination imposed minimal toxicity. Trial registration This trial was prospectively registered in IRCT.ir (IRCT2017100136491N1). Date of registration: 19 November 2017.
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Affiliation(s)
- Dena Firouzabadi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirreza Dehghanian
- Trauma Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Molecular Pathology and Cytogenetics Section, Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Alireza Rezvani
- Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. .,Hematology and Medical Oncology Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Laleh Mahmoudi
- Department of Clinical Pharmacy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Abdolrasoul Talei
- Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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The Presence of an In Situ Component on Pre-Treatment Biopsy Is Not Associated with Response to Neoadjuvant Chemotherapy for Breast Cancer. Cancers (Basel) 2021; 13:cancers13020235. [PMID: 33435265 PMCID: PMC7827327 DOI: 10.3390/cancers13020235] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/25/2020] [Accepted: 01/06/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Identifying markers predictive of response and resistance to neoadjuvant chemotherapy (NAC) has become a major research objective. Ductal carcinoma in situ (DCIS) is associated with invasive disease in more than half of invasive breast cancer cases. It is generally assumed that DCIS does not respond to NAC, but the effect of chemotherapy on in situ components has been little studied. We assessed the predictive value of the presence of an in situ component on pre-NAC biopsy on pathological complete response (pCR) in a real-life cohort of patients treated by NAC. We included 1148 patients; 44% of tumors were luminal (n = 508), 31% triple negative breast cancer (TNBC) (n = 359) and 24% HER2-positive (n = 281). DCIS was found in 225 samples (19.6%) before NAC. The presence of a DCIS component on pre-NAC biopsy was not associated with pCR and did not seem to be a critical factor for the prediction of response to NAC. Abstract A ductal in situ (DCIS) component is often associated with invasive breast carcinoma (BC), and its effect on response to treatment is unknown. We assessed the predictive value of the DCIS component for pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC). We analyzed a cohort of 1148 T1–3NxM0 breast cancer (BC) patients treated by NAC at Institut Curie between 2002 and 2012. The presence of a DCIS component was retrospectively recorded from both the pre-NAC biopsy pathological report and surgical specimens. We included 1148 BC patients treated by NAC for whom pre- and post-NAC data concerning the in situ component were available. DCIS was present before NAC in 19.6% of the population. Overall, 283 patients (19.4%) achieved pCR after NAC. There was no significant association between the presence of DCIS on pre-NAC biopsy and pCR. In a multivariate analysis including subtype, tumor size, grade, mitotic index, and Ki67 index, only BC subtype (luminal/TNBC/HER2-positive) and Ki67 were significantly associated with pCR. The presence of a DCIS component on pre-NAC biopsy is not associated with pCR and does not seem to be a critical factor for predicting response to NAC.
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Ray D, Gupta S, De A, Jain P, Bhattacharya N, Biswas P. Tumor infiltrating lymphocytes profile and response in neoadjuvant chemotherapy-treated triple-negative breast carcinoma patients. J Cancer Res Ther 2021; 18:1782-1788. [DOI: 10.4103/jcrt.jcrt_997_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Skarping I, Förnvik D, Heide-Jørgensen U, Rydén L, Zackrisson S, Borgquist S. Neoadjuvant breast cancer treatment response; tumor size evaluation through different conventional imaging modalities in the NeoDense study. Acta Oncol 2020; 59:1528-1537. [PMID: 33063567 DOI: 10.1080/0284186x.2020.1830167] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Neoadjuvant chemotherapy (NACT) is offered to an increasing number of breast cancer (BC) patients, and comprehensive monitoring of treatment response is of utmost importance. Several imaging modalities are available to follow tumor response, although likely to provide different clinical information. We aimed to examine the association between early radiological response by three conventional imaging modalities and pathological complete response (pCR). Further, we investigated the agreement between these modalities pre-, during, and post-NACT, and the accuracy of predicting pathological residual tumor burden by these imaging modalities post-NACT. MATERIAL AND METHODS This prospective Swedish cohort study included 202 BC patients assigned to NACT (2014-2019). Breast imaging with clinically used modalities: mammography, ultrasound, and tomosynthesis was performed pre-, during, and post-NACT. We investigated the agreement of tumor size by the different imaging modalities, and their accuracy of tumor size estimation. Patients with a radiological complete response or radiological partial response (≥30% decrease in tumor diameter) during NACT were classified as radiological early responders. RESULTS Patients with an early radiological response by ultrasound had 2.9 times higher chance of pCR than early radiological non-responders; the corresponding relative chance for mammography and tomosynthesis tumor size measures was 1.8 and 2.8, respectively. Post-NACT, each modality, separately, could accurately estimate tumor size (within 5 mm margin compared to pathological evaluation) in 43-46% of all tumors. The diagnostic precision in predicting pCR post-NACT was similar between the three imaging modalities; however, tomosynthesis had slightly higher specificity and positive predictive values. CONCLUSION Breast imaging modalities correctly estimated pathological tumor size in less than half of the tumors. Based on this finding, predicting residual tumor size post-NACT is challenging using conventional imaging. Patients with early radiological non-response might need improved monitoring during NACT and be considered for changed treatment plans.
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Affiliation(s)
- Ida Skarping
- Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden
| | - Daniel Förnvik
- Department of Translational Medicine, Medical Radiation Physics, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Uffe Heide-Jørgensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Lisa Rydén
- Department of Surgery, Lund University, Skåne University Hospital, Lund, Sweden
| | - Sophia Zackrisson
- Department of Translational Medicine, Diagnostic Radiology, Lund University, Skåne University Hospital, Lund, Sweden
- Department of Translational Medicine, Diagnostic Radiology, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Signe Borgquist
- Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Skåne University Hospital, Lund, Sweden
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
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Arici S, Sengiz Erhan S, Geredeli C, Cekin R, Sakin A, Cihan S. The Clinical Importance of Androgen Receptor Status in Response to Neoadjuvant Chemotherapy in Turkish Patients with Local and Locally Advanced Breast Cancer. Oncol Res Treat 2020; 43:435-440. [PMID: 32570261 DOI: 10.1159/000508478] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2019] [Accepted: 04/28/2020] [Indexed: 11/19/2022]
Abstract
PURPOSE To investigate whether androgen receptor (AR) status affects neoadjuvant chemotherapy (NACT) in stage II and III Turkish breast cancer patients. METHODS The histological response for breast and axilla was assessed according to the Miller-Payne grading system. In light microscopy, nuclear staining in tumor cells was evaluated, and nuclear staining above 1% was accepted as positive for AR expression. The patients were divided into 3 groups according to the intensity of AR staining: low, moderate, and high. RESULTS In total, 71 women with breast cancer were included in the study. In univariate analysis, age, menopause status, tumor diameter, stage, histological grade, Ki-67, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER-2) status were tested to determine which of these factors were associated with >90% responsiveness. AR negativity was found to be the only statistically significant factor. In multivariate analysis, AR positivity at each intensity was found to be the single important factor affecting decreasing pathologic response in patients receiving NACT for breast cancer. CONCLUSION Our results show that AR positivity is associated with poor response to NACT in Turkish breast cancer patients and that AR positivity is independent of stage, hormone receptor status, HER-2 status, and disease stage.
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Affiliation(s)
- Serdar Arici
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey,
| | - Selma Sengiz Erhan
- Department of Pathology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Caglayan Geredeli
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Ruhper Cekin
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Abdullah Sakin
- Department of Medical Oncology, Yuzuncu Yil University Medical School, Van, Turkey
| | - Sener Cihan
- Department of Medical Oncology, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
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Xia LY, Hu QL, Zhang J, Xu WY, Li XS. Survival outcomes of neoadjuvant versus adjuvant chemotherapy in triple-negative breast cancer: a meta-analysis of 36,480 cases. World J Surg Oncol 2020; 18:129. [PMID: 32539858 PMCID: PMC7296918 DOI: 10.1186/s12957-020-01907-7] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 06/04/2020] [Indexed: 12/14/2022] Open
Abstract
Background The survival outcomes of neoadjuvant chemotherapy (NACT) versus adjuvant chemotherapy (ACT) for patients with triple-negative breast cancer (TNBC) remain unclear. Therefore, in this study, a meta-analysis was conducted to analyze current evidence on the survival outcomes of NACT versus ACT in TNBC. Methods A systematic search was performed on the PubMed and Embase databases to identify relevant articles investigating the survival outcomes of NACT versus ACT in TNBC. Results A total of nine studies involving 36,480 patients met the selection criteria. Among them, 10,728 (29.41%) received NACT, and 25,752 (70.59%) received ACT. The pathological complete response (pCR) rate was 35% (95% CI = 0.23–0.48). Compared with ACT, the overall survival (OS) of NACT was poor (HR = 1.59; 95% CI = 1.25–2.02; P = 0.0001), and there was no significant difference in disease-free survival (DFS) between the two treatments (HR = 0.85; 95% CI = 0.54–1.34; P = 0.49). NACT with pCR significantly improved the OS (HR = 0.53; 95% CI = 0.29–0.98; P = 0.04) and DFS (HR = 0.52; 95% CI = 0.29–0.94; P = 0.03), while the OS (HR = 1.18; 95% CI = 1.09–1.28; P < 0.0001) and DFS (HR = 2.36; 95% CI = 1.42–3.89; P = 0.0008) of patients with residual disease (RD) following NACT were worse compared to those receiving ACT. Conclusion These findings suggest that, for TNBC, NACT with pCR is superior to ACT in improving OS and DFS, and it turns to be opposite when patients are receiving NACT with RD.
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Affiliation(s)
- Lin-Yu Xia
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Avenue Middle Section, Xindu District, Chengdu City, 610500, Sichuan Province, China.
| | - Qing-Lin Hu
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Avenue Middle Section, Xindu District, Chengdu City, 610500, Sichuan Province, China
| | - Jing Zhang
- Department of Breast Surgery, Mianyang Central Hospital, Mianyang, Sichuan, China
| | - Wei-Yun Xu
- Department of Breast Surgery, Mianyang Central Hospital, Mianyang, Sichuan, China
| | - Xiao-Shi Li
- Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Chengdu Medical College, 278 Baoguang Avenue Middle Section, Xindu District, Chengdu City, 610500, Sichuan Province, China
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Chaudhary LN. Early stage triple negative breast cancer: Management and future directions. Semin Oncol 2020; 47:201-208. [PMID: 32507668 DOI: 10.1053/j.seminoncol.2020.05.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 05/05/2020] [Accepted: 05/05/2020] [Indexed: 12/31/2022]
Abstract
Triple negative breast cancer is the most aggressive kind of breast cancer with high risk of recurrences and poor outcomes. Systemic chemotherapy has significantly improved long term outcomes in early stage patients; however, metastatic recurrences still develop in a significant number of patients. Anthracycline and taxane based chemotherapy regimens are standard of care for early stage patients. Neoadjuvant treatment is preferred due to the ability to assess pathologic responses providing important prognostic information and guidance in adjuvant therapy decisions. Carboplatin addition to the anthracycline and taxane backbone is associated with a significant improvement in pathologic complete response but is associated with more toxicity. Understanding the immune microenvironment of triple negative disease is an exciting field and immune checkpoint inhibitors have shown great promise in further improving response rates in early stage patients. Patients with residual disease after neoadjuvant chemotherapy have a significantly higher risk of recurrence compared to those with complete responses. Adjuvant capecitabine for these high-risk patients have shown significant improvement in long term outcomes and is routinely used in this setting. Given the heterogeneity within triple negative tumors, molecular subtypes with variable genomic makeup and chemo sensitivities have been identified and will likely aid in further clinical developmental therapeutics.
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Affiliation(s)
- Lubna N Chaudhary
- Division of Hematology/Oncology, Froedtert and Medical College of Wisconsin, Milwaukee, WI.
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Basnet B, Goyal P, Mahawar V, Bothra SJ, Agrawal C, Thapa BB, Talwar V, Jain P, Babu Koyyala VP, Goel V, Batra U, Doval DC. Role of 18F-Flurodeoxyglucose Positron-Emission Tomography/Computed Tomography in the Evaluation of Early Response to Neoadjuvant Chemotherapy in Patients with Locally Advanced Triple-Negative Breast Cancer. INDIAN JOURNAL OF NUCLEAR MEDICINE : IJNM : THE OFFICIAL JOURNAL OF THE SOCIETY OF NUCLEAR MEDICINE, INDIA 2020; 35:105-109. [PMID: 32351263 PMCID: PMC7182325 DOI: 10.4103/ijnm.ijnm_210_19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/28/2019] [Accepted: 01/14/2020] [Indexed: 11/09/2022]
Abstract
Background: Response evaluation in locally advanced breast cancer is done through different methods ranging from clinical examination to magnetic resonance imaging, however evaluation with positron-emission tomography/computed tomography (PET/CT) in now being incorporated for the response evaluation. The aim of the present study is to correlate response to neoadjuvant chemotherapy (NACT) with PET/CT scan. Materials and Methods: The present study is a retrospective analysis of 30 locally advanced, triple-negative breast cancer patients. PET/CT scan was done pretreatment and post three and six cycles of NACT and was correlated with pathologic complete response (pCR). Responding disease was considered when there was at least a 50% reduction in the longest diameter. Results: The median pretreatment size of the breast lesion in CT scan was 3.9 ± 2.3 cm (2–12 cm) and maximum standardized uptake value (SUVmax) on PET/CT was 8.5 ± 5.5 (2.9–24). Among the responders, the median decrease in size of lesion was 3.2 ± 1.3 cm and median reduction in SUV of the tumor among was −8.1 ± 5.4 and was statistically significant when compared with nonresponders (P < 0.001). CT scan has 66% accuracy and PET has 82% accuracy at post three cycles NACT in predicting the pathological response. PET/CT had higher sensitivity and specificity when compared with CT findings alone in response evaluation. Conclusion: PET/CT scan can be considered as a sensitive tool for predicting pCRs and further larger trials are required to establish these findings.
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Affiliation(s)
- Bina Basnet
- Department of Radiology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Pankaj Goyal
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Vivek Mahawar
- Department of Radiology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Sneha Jatan Bothra
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Chaturbhuj Agrawal
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Bikash Bikram Thapa
- Department of Surgical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Vineet Talwar
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Parveen Jain
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | | | - Varun Goel
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Ullas Batra
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Dinesh Chandra Doval
- Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
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Mukai H, Yamaguchi T, Takahashi M, Hozumi Y, Fujisawa T, Ohsumi S, Akabane H, Nishimura R, Takashima T, Park Y, Sagara Y, Toyama T, Imoto S, Mizuno T, Yamashita S, Fujii S, Uemura Y. Ki-67 response-guided preoperative chemotherapy for HER2-positive breast cancer: results of a randomised Phase 2 study. Br J Cancer 2020; 122:1747-1753. [PMID: 32238920 PMCID: PMC7283228 DOI: 10.1038/s41416-020-0815-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 01/15/2020] [Accepted: 03/12/2020] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND The effectiveness of a therapeutic strategy that switches chemotherapy, based on Ki-67 tumour expression after initial therapy, relative to that of standard chemotherapy, has not been evaluated. METHODS Patients were randomly assigned to the control arm or the Ki-67 response-guided arm (Ki-67 arm). Primary tumour biopsies were obtained before treatment, and after three once-weekly doses of paclitaxel and trastuzumab to assess the interim Ki-67 index. In the control arm, paclitaxel and trastuzumab were continued for a total of 12 doses, regardless of the interim Ki-67 index. In the Ki-67 arm, subsequent treatment was based on the interim Ki-67 index. Ki-67 early responder is defined as the absolute Ki-67 value that was <10%, and the percentage of Ki-67-positive tumour cells was reduced by >30% compared with before treatment. Early Ki-67 responders continued to receive the same treatment, while early Ki-67 non-responders were switched to epirubicin plus cyclophosphamide. The primary endpoint was the pathological complete response (pCR) rate. RESULTS A total of 237 patients were randomised. There was almost linear correlation between the Ki-67 reduction rate at interim assessment and the pCR rate. The pCR rate in Ki-67 early non-responders in the Ki-67 arm was inferior to that in the control arm (44.1%; 31.4-56.7; P = 0.025). CONCLUSIONS The standard chemotherapy protocol remains as the recommended strategy for patients with HER2-positive breast cancer. CLINICAL TRIAL REGISTRATION Clinical Trial Registration: UMIN-CTR as UMIN000007074.
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Affiliation(s)
- Hirofumi Mukai
- National Cancer Center Hospital East, Kashiwa, Chiba, 277-8577, Japan.
| | | | - Masato Takahashi
- National Hospital Organization Hokkaido Cancer Center, Sapporo, Hokkaido, 003-0804, Japan
| | - Yasuo Hozumi
- University of Tsukuba Hospital, Tsukuba, Ibaraki, 305-8576, Japan
| | - Tomomi Fujisawa
- Gunma Prefectural Cancer Center, Ota, Gunma, 373-0828, Japan
| | - Shozo Ohsumi
- National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, 791-0245, Japan
| | | | - Reiki Nishimura
- Kumamoto Shinto General Hospital, Chuo Ward, Kumamoto, 862-8655, Japan
| | - Tsutomu Takashima
- Osaka City University Graduate School of Medicine, Sumiyoshi Ward, Osaka, 558-0022, Japan
| | - Youngjin Park
- Tohoku Medical and Pharmaceutical University Hospital, Sendai, Miyagi, 981-8558, Japan
| | - Yasuaki Sagara
- Hakuaikai Medical Corp Sagara Hospital, Kagoshima, Japan
| | - Tatsuya Toyama
- Nagoya City University Graduate School of Medical Sciences, Aichi, Nagoya, 467-8601, Japan
| | - Shigeru Imoto
- Kyorin University Hospital, Mitaka, Tokyo, 181-8611, Japan
| | | | - Satoshi Yamashita
- National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan
| | - Satoshi Fujii
- Division of Pathology, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan
| | - Yukari Uemura
- National Center for Global Health and Medicine, Tokyo, Japan
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Yang L, Fu B, Li Y, Liu Y, Huang W, Feng S, Xiao L, Sun L, Deng L, Zheng X, Ye F, Bu H. Prediction model of the response to neoadjuvant chemotherapy in breast cancers by a Naive Bayes algorithm. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2020; 192:105458. [PMID: 32302875 DOI: 10.1016/j.cmpb.2020.105458] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 02/17/2020] [Accepted: 03/16/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND OBJECTIVE Chemotherapy is useful to many breast cancer patients, however, it is not therapeutic for some patients. Pathologic complete response (pCR) is an indicator to good response in Neoadjuvant chemotherapy (NAC). In this study, we aimed to develop a way to predict pCR before NAC. METHODS We retrospectively collected 287 stage II-III breast cancer cases either to a training set (N = 197) or to a test set (N = 90). Fourteen candidate genes were selected from four public microarray data sets. A prediction model was built, by using these fourteen candidate genes and three reference genes expression which were tested by TaqMan probe-based quantitative polymerase chain reaction, after selecting a better algorithm. RESULTS The Naive Bayes algorithm had a relatively higher predictive value, compared with random forest, support vector machine (SVM), and k-nearest neighbor (knn) algorithms (P < 0.05). This 17-gene prediction model showed a high positive correlation with pCR (odds ratio, 8.914, 95% confidence interval, 4.430-17.934, P < 0.001). By using this model, the enrolled patients were classified into sensitive (SE) and insensitive (INS) groups. The pCR rates between the SE and INS groups were highly different (42.3% vs.7.6%, P < 0.001). The sensitivity and specificity of this prediction model were 84.5% and 62.0%. CONCLUSIONS Instead of whole transcriptome-based technologies, panel gene expression with tens of essential genes implemented in a machine learning model has predictive potential for chemosensitivity in breast cancers.
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Affiliation(s)
- Libo Yang
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China; Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China; Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Bo Fu
- Big Data Research Center, School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Yan Li
- Big Data Research Center, School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu, China
| | - Yueping Liu
- Department of Pathology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Wenting Huang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100021, China
| | - Sha Feng
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Shenzhen 518116, China
| | - Lin Xiao
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China; Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China
| | - Linyong Sun
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Ling Deng
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China; Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China
| | - Xinyi Zheng
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China; Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China
| | - Feng Ye
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China; Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China.
| | - Hong Bu
- Laboratory of Pathology, West China Hospital, Sichuan University, Chengdu, China; Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, China; Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
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Arispe Angulo KR, Jawa Z, Visotcky A, Majidi SS, Chitambar CR, Jorns JM. A high mitotic score in breast cancer after neoadjuvant chemotherapy is predictive of outcome and associated with a distinct morphology. Histopathology 2020; 76:661-670. [PMID: 31849088 DOI: 10.1111/his.14049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2019] [Revised: 11/14/2019] [Accepted: 12/13/2019] [Indexed: 11/28/2022]
Abstract
AIMS Neoadjuvant chemotherapy (NAC) is frequently used for the treatment of breast cancer. We sought to analyse the clinical, morphological and immunohistochemical features of tumours from patients who did not achieve pathological complete response following NAC. METHODS AND RESULTS We identified stage I-III post-NAC breast cancers from surgical resections (2000-2016) with evaluable residual invasive carcinoma [ypT1a(m) or greater and ≥15% tumour cellularity]. One hundred and forty-three tumours from 142 patients were included. On univariable analysis, a high (score 3) post-NAC mitotic score (as compared with 1 or 2) was significantly associated with invasive ductal carcinoma (IDC) subtype (P = 0.023), high grade, pushing borders with zones of necrosis, hormone receptor and triple-negative status, lack of hormonal therapy, higher cellularity (P < 0.001), and a higher percentage of tumour-infiltrating lymphocytes (P = 0.016). Multivariable analysis showed a high post-NAC mitotic score to be significantly associated with recurrence, distant metastasis, and shortened survival (hazard ratios of 5.73, 4.49, and 3.68, respectively). High post-NAC mitotic score tumours (n = 32) were IDC and had a high Ki67 proliferation index (median, 55%). Of these, 24 (75%) had pushing borders with zones of necrosis; 19 (79.2%) of these had necrosis on preoperative imaging, and 24 (75%), 15 (46.9%) and four (12.5%) lacked androgen receptor, GATA-3 and cytokeratin 18 expression, respectively. CONCLUSIONS High post-NAC mitotic score breast cancers cause high morbidity and mortality, frequently have pushing borders and zones of necrosis, and may show loss of common 'breast cancer markers'. Our findings support that necrosis in pretreatment studies and post-NAC mitotic score should be routinely reported, as they offer significant additional prognostic information to guide management.
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Affiliation(s)
| | | | - Alexis Visotcky
- Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Shadie S Majidi
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Christopher R Chitambar
- Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Julie M Jorns
- Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA
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Abstract
Breast cancer in young women requires special vigilance because of the unique condition and complex management that is involved. The indication for chemotherapy should not be based on age alone but in association with the biological characteristics of the tumour. In addition, age is not considered as demonstrated predictor of chemosensitivity. The choice of adjuvant or neoadjuvant chemotherapy should be guided by the histological type of the tumour, the stage of the tumour and the patient's comorbidities. In this subgroup of patients, the recommendations for the use of molecular signatures follow those of the general population. This manuscript summarizes the main data and recommendations on the management of breast cancer in young women in term of chemotherapy.
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Affiliation(s)
- Elise Deluche
- Institut Gustave-Roussy, Comité de pathologie mammaire, 114, rue Édouard-Vaillant, 94800 Villejuif, France.
| | - Jean-Yves Pierga
- Institut Curie, Département de médecine oncologique, 26, rue d'Ulm 75005 Paris, France
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50
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Skarping I, Förnvik D, Sartor H, Heide-Jørgensen U, Zackrisson S, Borgquist S. Mammographic density is a potential predictive marker of pathological response after neoadjuvant chemotherapy in breast cancer. BMC Cancer 2019; 19:1272. [PMID: 31888552 PMCID: PMC6937786 DOI: 10.1186/s12885-019-6485-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 12/20/2019] [Indexed: 12/12/2022] Open
Abstract
Background Our aim is to study if mammographic density (MD) prior to neoadjuvant chemotherapy is a predictive factor in accomplishing a pathological complete response (pCR) in neoadjuvant-treated breast cancer patients. Methods Data on all neoadjuvant treated breast cancer patients in Southern Sweden (2005–2016) were retrospectively identified, with patient and tumor characteristics retrieved from their medical charts. Diagnostic mammograms were used to evaluate and score MD as categorized by breast composition with the Breast Imaging-Reporting and Data System (BI-RADS) 5th edition. Logistic regression was used in complete cases to assess the odds ratios (OR) for pCR compared to BI-RADS categories (a vs b-d), adjusting for patient and pre-treatment tumor characteristics. Results A total of 302 patients were included in the study population, of which 57 (18.9%) patients accomplished pCR following neoadjuvant chemotherapy. The number of patients in the BI-RADS category a, b, c, and d were separately 16, 120, 140, and 26, respectively. In comparison to patients with BI-RADS breast composition a, patients with denser breasts had a lower OR of accomplishing pCR: BI-RADS b 0.32 (95%CI 0.07–0.1.5), BI-RADS c 0.30 (95%CI 0.06–1.45), and BI-RADS d 0.06 (95%CI 0.01–0.56). These associations were measured with lower point estimates, but wider confidence interval, in premenopausal patients; OR of accomplishing pCR for BI-RADS d in comparison to BI-RADS a: 0.03 (95%CI 0.00–0.76). Conclusions The likelihood of accomplishing pCR is indicated to be lower in breast cancer patients with higher MD, which need to be analysed in future studies for improved clinical decision-making regarding neoadjuvant treatment.
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Affiliation(s)
- Ida Skarping
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
| | - Daniel Förnvik
- Medical Radiation Physics, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden
| | - Hanna Sartor
- Diagnostic Radiology, Department of Translational Medicine, Lund University, Skåne University Hospital, Lund and Malmö, Sweden
| | - Uffe Heide-Jørgensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
| | - Sophia Zackrisson
- Diagnostic Radiology, Department of Translational Medicine, Lund University, Skåne University Hospital, Lund and Malmö, Sweden
| | - Signe Borgquist
- Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.,Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
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