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Wang Z, Zeng Y, Jiang H, Luo C, Zhang F, Zhu X, Fu Q. Management strategies for primary lung carcinosarcoma: a case study and comprehensive literature review. J Cancer Res Clin Oncol 2025; 151:147. [PMID: 40261422 DOI: 10.1007/s00432-025-06203-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 04/14/2025] [Indexed: 04/24/2025]
Abstract
BACKGROUND Primary lung carcinosarcoma, characterized by the presence of both carcinoma and sarcoma components, is a rare soft tissue malignancy. Its pathogenesis remains incompletely elucidated, and it exhibits significant resistance to conventional therapeutic interventions, resulting in a dismal prognosis. Consequently, there is currently no established standard treatment protocol for lung carcinosarcoma, leading most clinicians to draw upon their experiences with other tumor types when formulating treatment strategies. CASE DESCRIPTION A 56-year-old non-smoking male presented with a progressively enlarging mass in the right cervical region, The diagnosis of lung carcinosarcoma was definitively confirmed through CT-guided biopsy. First-line immunotherapy combined with targeted therapy was ineffective; second-line chemotherapy was effective, chest CT revealed the disappearance of enlarged lymph nodes in the retrosternal area and a significant reduction of pulmonary lesions, but showed signs of brain metastasis. the patient passed away at home on June 27th, 2023 due to sudden onset dyspnea accompanied by loss of consciousness. LITERATURE REVIEW A comprehensive literature search for lung carcinosarcoma was conducted across four databases, including PubMed/MEDLINE, Web of Science, Cochrane Library, and Embase, covering the period from 1968 to 2023. A total of 48 patients were included for analysis. Further survival analysis revealed a median survival time of 18 months; adjuvant therapy following surgery significantly improved survival compared to surgery alone and other treatment modalities. CONCLUSION Lung carcinosarcoma is an exceptionally rare malignant neoplasm of the lung, and definitive treatment protocols remain elusive. The most effective strategy to enhance prognosis may still entail complete surgical resection of the lesions in conjunction with adjuvant therapy.
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Affiliation(s)
- Zhonglian Wang
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan, 650032, People's Republic of China
| | - Ying Zeng
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan, 650032, People's Republic of China
| | - Hongting Jiang
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan, 650032, People's Republic of China
| | - Cha Luo
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan, 650032, People's Republic of China
| | - Fei Zhang
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan, 650032, People's Republic of China
| | - Xiaofeng Zhu
- Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, No. 2, 295 Xichang Road, Kunming, Yunnan, 650032, People's Republic of China.
| | - Qiaofen Fu
- Department of Radiation Oncology, The First Affiliated Hospital of Kunming Medical University, 295 Xichang Road, Kunming, Yunnan, 650032, People's Republic of China.
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Mastoraki A, Tsamopoulou M, Stamatis FK, Strimpakos A, Mouchtouri E, Panagi C, Mela E, Mastoraki S, Kechagias A, Schizas D. Carcinosarcoma of the breast: Facing the challenge of a rare nosologic entity. World J Clin Cases 2025; 13:99619. [PMID: 39823109 PMCID: PMC11577508 DOI: 10.12998/wjcc.v13.i2.99619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 10/02/2024] [Accepted: 10/20/2024] [Indexed: 11/08/2024] Open
Abstract
Carcinosarcoma (CS), also known as metaplastic breast carcinoma with mesenchymal differentiation, is one of the five distinct subtypes of metaplastic breast cancer. It is considered as a mixed, biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition zone. Although cellular origin of this neoplasm remains controversial, most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic differentiation. Despite recent research on the therapeutic strategies against CS neoplastic disorders, surgical resection appears the only potentially curative approach. Since CS metastasize by the lymphatic route, axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always implemented. Nevertheless, the tumor also presents a hematogenous metastatic pattern including pleural, pulmonary, liver, brain and less commonly bone metastases. Thus, surgical removal of breast CS does not necessarily ensure patient's long-term recovery. Moreover, alternative therapies, such as radio- and chemotherapy proved insufficient and 5-year survival rate is limited. Nevertheless, there is evidence that following surgery, the combination of radio and chemotherapy is associated with a better prognosis than either treatment alone. The aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological spread. Clinical features, histogenesis, morphological and immunochemical findings are discussed, while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.
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Affiliation(s)
- Aikaterini Mastoraki
- Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens 11527, Greece
| | - Maria Tsamopoulou
- Department of Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
| | | | | | - Ero Mouchtouri
- Department of Radiology, Henry Dunant Hospital Center, Athens 11526, Greece
| | - Christiana Panagi
- Department of Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Evgenia Mela
- Department of Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Sotiria Mastoraki
- Department of Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
| | | | - Dimitrios Schizas
- Department of Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
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Banerjee S, Mahajan I, Ghose A, Boussios S, Chakraborty S. A rare case of metaplastic breast carcinoma from India: Towards precision oncology. Cancer Rep (Hoboken) 2024; 7:e1997. [PMID: 38421154 PMCID: PMC10903326 DOI: 10.1002/cnr2.1997] [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: 08/10/2023] [Revised: 12/13/2023] [Accepted: 01/25/2024] [Indexed: 03/02/2024] Open
Abstract
BACKGROUND Metaplastic Breast Cancer (MpBC) is an exceedingly rare entity, accounting for less than 1% of all malignant breast tumours. Predominantly triple-negative, they are notorious for their chemoresistance, high rates of recurrence and decreased disease-free survival (DFS). All this contributes significantly to BC mortality and results in poor prognostic implications. Limited evidence has led to a lacuna of specific treatment guidelines for this entity and hence remains an uncharted territory for clinicians. CASE We report a case of a 46 year old premenopausal female with left-sided metaplastic triple negative T3N2aM0 BC with mesenchymal differentiation (high grade) whom we treated with neoadjuvant chemotherapy, primary surgery in the form of extreme oncoplasty and adjuvant radiotherapy by Telecobalt machine. Contrary to the expected aggressive course of the disease and poor prognosis of treatment, the patient is presently in remission without progression for over 2 years of follow up. CONCLUSION Limited experience in management of this pathological entity warrants the need for more research on it, with a special focus on targeted therapy. Discussing possibilities of a tailored approach, rather than a one-size-fits-all approach may aid in paving the path for the future of MpBC treatment.
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Affiliation(s)
- Soirindhri Banerjee
- Department of Radiation OncologyInstitute of Post Graduate Medical Education & Research and SSKM HospitalKolkataIndia
| | - Ishika Mahajan
- Department of Haematology and OncologyLincoln County Hospital, United Lincolnshire Hospitals TrustLincolnUK
| | - Aruni Ghose
- Department of Medical OncologyBarts Cancer Centre, St. Bartholomew's Hospital, Barts Health NHS TrustLondonUK
- Department of Medical OncologyMount Vernon Cancer Centre, East and North Hertfordshire NHS TrustLondonUK
- Department of Medical OncologyMedway NHS Foundation TrustKentUK
- United Kingdom and Ireland Global Cancer NetworkLondonUK
- Immuno‐Oncology Clinical NetworkKentUK
| | - Stergios Boussios
- Department of Medical OncologyMedway NHS Foundation TrustKentUK
- Faculty of Life Sciences and MedicineSchool of Cancer and Pharmaceutical Sciences, King's College LondonLondonUK
- Kent and Medway Medical SchoolUniversity of KentCanterburyUK
- AELIA OrganisationThessalonikiGreece
| | - Shivam Chakraborty
- Depatment of PathologyInstitute of Post Graduate Medical Education & Research and SSKM HospitalKolkataIndia
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Tang LS, Zhou YW, Wang JL, Zhang GX, Xu CH, Liu JY, Qiu M. Epidemiology, site-specific characteristics and survival of carcinosarcoma: a retrospective study based on SEER database. BMJ Open 2023; 13:e077974. [PMID: 38101828 PMCID: PMC10729011 DOI: 10.1136/bmjopen-2023-077974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 12/01/2023] [Indexed: 12/17/2023] Open
Abstract
OBJECTIVES Carcinosarcoma (CS) is a rare and biphasic malignancy characterised by a highly invasive biological nature and poor prognosis. This study explored the epidemiology, site-specific characteristics and survival outcome of CS. DESIGN We conducted a retrospective study in the Surveillance, Epidemiology and End Results (SEER) database (1975-2018) for primary CS. SETTING AND PARTICIPANTS SEER database includes publicly available information from regional and state cancer registries in the US centres. A total of 5042 CS patients were identified. We selected the top five anatomic CS (uterus, double adnexa, lung, bladder and breast) patients for further analysis. PRIMARY OUTCOME MEASURES Incidence was estimated by geographical region, age, sex, race, stage and primary site. Trends were calculated using joinpoint regression. The cancer-specific survival (CSS) rate and initial treatment were summarised. RESULTS Nearly 80% of CS occurred in the uterus and double adnexa, followed by lung, bladder and breast. The elderly and black population presented the highest age-adjusted rate of CS. The rates of distant metastasis in CS progressively increased from 1989 to 2018. Atlanta was the area with the highest incidence at 0.7 per 100 000. Pulmonary and bladder CS more frequently occurred in men and were diagnosed with regional stage. Distant metastasis was mostly found in ovary/fallopian tube CS. Radiotherapy was more commonly applied in uterine CS, while adnexa CS cases were more likely to receive chemotherapy. Multiple treatments were more used in breast CS. Pulmonary CS seemed to suffer worse CSS (median: 9.92 months), for which radiotherapy might not provide survival benefits (HR 0.60, 95% CI 0.42 to 0.86). Compared with the common histological types in each site, CS had the shortest survival. CONCLUSIONS CS has unique clinical features in each primary site. Substantial prognosis variances exist based on tumour locations. The aggressive course is the common feature in CS at all sites.
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Affiliation(s)
- Lian-Sha Tang
- West China Hospital of Sichuan University, Chengdu, China
| | - Yu-Wen Zhou
- Department of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Jia-Ling Wang
- West China Hospital of Sichuan University, Chengdu, China
| | - Guo-Xu Zhang
- West China Hospital of Sichuan University, Chengdu, China
| | - Chen-Hao Xu
- West China Hospital of Sichuan University, Chengdu, China
| | - Ji-Yan Liu
- Department of Biotherapy, West China Hospital of Sichuan University, Chengdu, China
| | - Meng Qiu
- Department of Abdominal Oncology, West China Hospital of Sichuan University, Chengdu, China
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Kumar B, Khatpe AS, Guanglong J, Batic K, Bhat-Nakshatri P, Granatir MM, Addison RJ, Szymanski M, Baldridge LA, Temm CJ, Sandusky G, Althouse SK, Cote ML, Miller KD, Storniolo AM, Nakshatri H. Stromal heterogeneity may explain increased incidence of metaplastic breast cancer in women of African descent. Nat Commun 2023; 14:5683. [PMID: 37709737 PMCID: PMC10502140 DOI: 10.1038/s41467-023-41473-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 09/05/2023] [Indexed: 09/16/2023] Open
Abstract
The biologic basis of genetic ancestry-dependent variability in disease incidence and outcome is just beginning to be explored. We recently reported enrichment of a population of ZEB1-expressing cells located adjacent to ductal epithelial cells in normal breasts of women of African ancestry compared to those of European ancestry. In this study, we demonstrate that these cells have properties of fibroadipogenic/mesenchymal stromal cells that express PROCR and PDGFRα and transdifferentiate into adipogenic and osteogenic lineages. PROCR + /ZEB1 + /PDGFRα+ (PZP) cells are enriched in normal breast tissues of women of African compared to European ancestry. PZP: epithelial cell communication results in luminal epithelial cells acquiring basal cell characteristics and IL-6-dependent increase in STAT3 phosphorylation. Furthermore, level of phospho-STAT3 is higher in normal and cancerous breast tissues of women of African ancestry. PZP cells transformed with HRasG12V ± SV40-T/t antigens generate metaplastic carcinoma suggesting that these cells are one of the cells-of-origin of metaplastic breast cancers.
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Affiliation(s)
- Brijesh Kumar
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
- School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, UP, 221005, India
| | - Aditi S Khatpe
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Jiang Guanglong
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Katie Batic
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | | | - Maggie M Granatir
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Rebekah Joann Addison
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Megan Szymanski
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Lee Ann Baldridge
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Constance J Temm
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - George Sandusky
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Sandra K Althouse
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Michele L Cote
- Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, 46202, USA
| | - Kathy D Miller
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Anna Maria Storniolo
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA
| | - Harikrishna Nakshatri
- Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
- VA Roudebush Medical Center, Indianapolis, IN, 46202, USA.
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Arekemase H, Mohammed O, Zafar U, Manpreet K, Maghari A. Metaplastic Breast Carcinoma Presenting as a Mixed Solid and Cystic Lesion. Cureus 2022; 14:e22029. [PMID: 35340469 PMCID: PMC8913436 DOI: 10.7759/cureus.22029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/07/2022] [Indexed: 11/05/2022] Open
Abstract
The objective of this paper is to report a rare presentation of metaplastic breast carcinoma (MBC) as a mixed solid/cystic mass and emphasize the possibility of having a different biopsy report and final diagnosis. MBC is a rare type of breast cancer consisting of mesenchymal or mixed mesenchymal and epithelial components. It is believed to result from the conversion of glandular cells into non-glandular cells through various forms of mutations. It is common in females and more frequent in older women. MBC is a triple-negative breast cancer (progestin receptor, estrogen receptor, and human epidermal growth factor receptor 2) with a very poor prognosis when compared with other types of breast cancers. This is a case of an 84-year-old woman presenting with rapidly growing mixed solid and cystic breast mass with a final diagnosis of MBC. The initial biopsy report was high-grade ductal carcinoma in situ. This is an unusual presentation of MBC.
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Assunção Ribeiro da Costa RE, da Silva Fontinele DR, Medeiros PCDR, Vieira SC. Survival in metaplastic breast carcinoma: A case series. Breast Dis 2021; 41:133-136. [PMID: 34864646 DOI: 10.3233/bd-210040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Metaplastic breast carcinoma (MBC) is a rare type of breast cancer (0.20-1.00% of all cases). With a more aggressive clinical course, MBC frequently presents as a triple-negative subtype. OBJECTIVE To describe a case series, analyzing patients survival in four MBC cases. METHODS The cases were obtained from 532 medical records of breast cancer patients (0.7% of the total). RESULTS All patients were female. Mean patient age was 49 years (range: 38-60 years). Mean tumor size was 8.9 cm (range: 3.0-15.5 cm). Mastectomy was performed in three cases. One patient had axillary nodal metastasis. All underwent chemotherapy and three received radiation therapy after surgery. CONCLUSIONS With a mean follow-up of 36 months (range: 10-60 months), one case had a tumor recurrence (25%). Three patients (75%) died from metastatic disease and one (25%) is still alive and free of disease.
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8
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Gortman A, Aherne NJ, Westhuyzen J, Amalaseelan JV, Dwyer PM, Hoffmann M, Last AT, Shakespeare TP. Metaplastic carcinoma of the breast: Clinicopathological features and treatment outcomes with long-term follow up. Mol Clin Oncol 2021; 15:178. [PMID: 34276997 DOI: 10.3892/mco.2021.2340] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 02/15/2021] [Indexed: 12/24/2022] Open
Abstract
Metaplastic breast carcinoma is an uncommon subtype of invasive ductal carcinoma with a tendency towards poorer clinical outcomes. Following ethical approval, the current study reviewed the institutional records of ~2,500 women with breast cancer. A total of 14 cases of metaplastic breast cancer were reviewed for management and treatment outcomes. The results demonstrated that patients had median follow up of 30 months, a 5-year disease-free survival of 57.1% and 5-year overall survival of 57.1%. The majority of patients had at least T2 disease and all tumours were high grade. Additionally, most patients were triple negative and nodal metastases were uncommon. Metaplastic breast cancer is an aggressive variant of invasive breast cancer. Most patients can be treated with breast conservation and survival parameters tend to be worse than more common breast cancer subtypes.
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Affiliation(s)
- Aron Gortman
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales 2450, Australia
| | - Noel J Aherne
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales 2450, Australia.,Rural Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2450, Australia.,School of Health and Human Sciences, Southern Cross University, Coffs Harbour, New South Wales 2450, Australia
| | - Justin Westhuyzen
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales 2450, Australia
| | - Julan V Amalaseelan
- Department of Radiation Oncology, North Coast Cancer Institute, Lismore, New South Wales 2480, Australia
| | - Patrick M Dwyer
- Department of Radiation Oncology, North Coast Cancer Institute, Lismore, New South Wales 2480, Australia
| | - Matthew Hoffmann
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Port Macquarie, New South Wales 2444, Australia
| | - Andrew T Last
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Port Macquarie, New South Wales 2444, Australia
| | - Thomas P Shakespeare
- Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales 2450, Australia.,Rural Clinical School, Faculty of Medicine, University of New South Wales, New South Wales 2450, Australia
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9
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McMullen ER, Zoumberos NA, Kleer CG. Metaplastic Breast Carcinoma: Update on Histopathology and Molecular Alterations. Arch Pathol Lab Med 2020; 143:1492-1496. [PMID: 31765246 DOI: 10.5858/arpa.2019-0396-ra] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
CONTEXT— Metaplastic carcinoma is a rare, triple-negative carcinoma of the breast that exhibits transformation of part or all of its glandular carcinomatous component into a nonglandular, or metaplastic, component. The World Health Organization currently recognizes 5 variants of metaplastic carcinoma based on their histologic appearance. OBJECTIVE— To review the histologic classifications, differential diagnosis, prognosis, and recent laboratory studies of metaplastic breast carcinoma. DATA SOURCES.— We reviewed recently published studies that collectively examine metaplastic carcinomas, including results from our own research. CONCLUSIONS.— Metaplastic breast carcinoma has a broad spectrum of histologic patterns, often leading to a broad differential diagnosis. Diagnosis can typically be rendered by a combination of morphology and immunohistochemical staining for high-molecular-weight cytokeratins and p63. Recent studies elucidate new genes and pathways involved in the pathogenesis of metaplastic carcinoma, including the downregulation of CCN6 and WNT pathway gene mutations, and provide a novel MMTV-Cre;Ccn6fl/fl knockout disease-relevant mouse model to test new therapies.
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Affiliation(s)
- Emily R McMullen
- From the Department of Pathology (Drs McMullen, Zoumberos, and Kleer) and Rogel Cancer Center (Dr Kleer), University of Michigan Medical School, Ann Arbor
| | - Nicholas A Zoumberos
- From the Department of Pathology (Drs McMullen, Zoumberos, and Kleer) and Rogel Cancer Center (Dr Kleer), University of Michigan Medical School, Ann Arbor
| | - Celina G Kleer
- From the Department of Pathology (Drs McMullen, Zoumberos, and Kleer) and Rogel Cancer Center (Dr Kleer), University of Michigan Medical School, Ann Arbor
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Quantitative proteomic landscape of metaplastic breast carcinoma pathological subtypes and their relationship to triple-negative tumors. Nat Commun 2020; 11:1723. [PMID: 32265444 PMCID: PMC7138853 DOI: 10.1038/s41467-020-15283-z] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 02/28/2020] [Indexed: 12/15/2022] Open
Abstract
Metaplastic breast carcinoma (MBC) is a highly aggressive form of triple-negative cancer (TNBC), defined by the presence of metaplastic components of spindle, squamous, or sarcomatoid histology. The protein profiles underpinning the pathological subtypes and metastatic behavior of MBC are unknown. Using multiplex quantitative tandem mass tag-based proteomics we quantify 5798 proteins in MBC, TNBC, and normal breast from 27 patients. Comparing MBC and TNBC protein profiles we show MBC-specific increases related to epithelial-to-mesenchymal transition and extracellular matrix, and reduced metabolic pathways. MBC subtypes exhibit distinct upregulated profiles, including translation and ribosomal events in spindle, inflammation- and apical junction-related proteins in squamous, and extracellular matrix proteins in sarcomatoid subtypes. Comparison of the proteomes of human spindle MBC with mouse spindle (CCN6 knockout) MBC tumors reveals a shared spindle-specific signature of 17 upregulated proteins involved in translation and 19 downregulated proteins with roles in cell metabolism. These data identify potential subtype specific MBC biomarkers and therapeutic targets. Metaplastic breast carcinoma (MBC) is among the most aggressive subtypes of triple-negative breast cancer (TNBC) but the underlying proteome profiles are unknown. Here, the authors characterize the protein signatures of human MBC tissue samples and their relationship to TNBC and normal breast tissue.
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11
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Al Sayed AD, Elshenawy MA, Tulbah A, Al-Tweigeri T, Ghebeh H. Complete Response of Chemo-Refractory Metastatic Metaplastic Breast Cancer to Paclitaxel-Immunotherapy Combination. AMERICAN JOURNAL OF CASE REPORTS 2019; 20:1630-1635. [PMID: 31690713 PMCID: PMC6858626 DOI: 10.12659/ajcr.918770] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Patient: Female, 49 Final Diagnosis: Metastatic metaplastic breast cancer Symptoms: Progressive right breast mass Medication: 5-fluorouracil • Cytoxan • Epirubicin (FEC 100) • Docetaxel • Capecitabine Clinical Procedure: Mastectomy • Radiation Therapy Specialty: Oncology
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Affiliation(s)
- Adher D Al Sayed
- Department of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Mahmoud A Elshenawy
- Department of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.,Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Asma Tulbah
- Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Taher Al-Tweigeri
- Department of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Hazem Ghebeh
- Stem Cell and Tissue Re-Engineering Program, Research Centre, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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