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1
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Andour L, Hagenaars SC, Vangangelt K, Aalberts J, Rebattu V, van der Meer DMAB, Kranenbarg EM, Gaarenstroom KN, van Asperen CJ, Tollenaar RAEM, Mesker WE. The TESTBREAST journey: Revisiting the importance of early detection by frequent screening of women at high risk of breast cancer. Int J Cancer 2025; 157:741-751. [PMID: 40232159 PMCID: PMC12178100 DOI: 10.1002/ijc.35444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Collaborators] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 03/13/2025] [Accepted: 03/26/2025] [Indexed: 04/16/2025]
Abstract
Women with an inherited pathogenic variant (PV) in a breast cancer (BC) susceptibility gene, or familial predisposition (FP) have an increased risk to develop BC. There is a need for improvement of screening methods due to interval cancers and radiation exposure. The aim of the TESTBREAST study is to develop a blood test suitable for early diagnosis. Here, the clinical composition of participants is provided. From 2010 to 2022, 1108 women were included in the TESTBREAST study, with currently 750 participants suitable for serum analysis. The median follow-up was 7 years [1-14]. Of the 1108 participants, 70% (n = 728) had a PV. BC was diagnosed in 16.5% (n = 124), mainly stage I-II (68.5%), and mostly BRCA1 (n = 47, 47%) and BRCA2 (n = 29, 29%) carriers. Invasive cancer was diagnosed in 100 cases: 76% (n = 76) had a PV with a median age of 49 [26-68] at diagnosis, whereas 24% (n = 24) had a FP, with a median age of 51 years [25-65]. The general population (the Netherlands) is aged 61 years on average at diagnosis. Triple negative breast cancer (TNBC) occurred in 51% (n = 39) of the TESTBREAST women with a PV, whereas this was 11% in the general population. Within the TESTBREAST cohort, BRCA carriers were younger at diagnosis and often had the aggressive TNBC subtype. Improvement of current screening methods for early detection is especially important for this group of high-risk women to reduce interval cancers, exposure to radiation, and to improve survival.
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Affiliation(s)
- Layla Andour
- Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
| | | | - Kiki Vangangelt
- Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
| | - Janneke Aalberts
- Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
| | - Valerie Rebattu
- Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
| | | | | | - Katja N. Gaarenstroom
- Department of Obstetrics and GynecologyLeiden University Medical CenterLeidenThe Netherlands
| | | | | | - Wilma E. Mesker
- Department of SurgeryLeiden University Medical CenterLeidenThe Netherlands
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Collaborators
J Aalberts, T M A Berends-van der Meer, S C Hagenaars, L Andour, W E Mesker, R A E M Tollenaar, W M Meershoek-Klein Kranenbarg, K N Gaarenstroom, C M R Haekens, K B M I Keymeulen, J Remmelzwaal, M Piek-den Hartog, E J T Rutgers, C Drukker, C Lemstra, A Prozee, J de Vries, A Stam, C Bandel, I Meijer, A E Dassen, S Makineli, E E van Oers-Hazelzet, A J Witkamp, K E Schenk, W van der Eijk, M B E Menke-Pluijmers, J de Droog-Laane, B A Kortmann,
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Sacchini V. Risk-reducing surgery in BRCA carriers: do we need more evidence? Lancet Oncol 2025; 26:671-673. [PMID: 40347972 DOI: 10.1016/s1470-2045(25)00232-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2025] [Accepted: 04/15/2025] [Indexed: 05/14/2025]
Affiliation(s)
- Virgilio Sacchini
- Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
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3
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Chiarella LS, Huelsboemer L, Diatta F, Klimitz FJ, Kammien AJ, Kochen A, Boroumand S, Allam O, Kauke-Navarro M, Pomahac B. The Five-Item Modified Frailty Index Predicts Adverse Surgical Outcomes in Patients Undergoing Mastectomy. Ann Surg Oncol 2025:10.1245/s10434-025-17105-2. [PMID: 40342005 DOI: 10.1245/s10434-025-17105-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 02/17/2025] [Indexed: 05/11/2025]
Abstract
BACKGROUND The 5-item modified Frailty Index (mFI-5) is a clinical tool to predict adverse outcomes in surgical patients by assessing five comorbidities: diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and dependent functional status. It helps to evaluate postoperative complication risks, recovery time, and overall survival, particularly in frail patients undergoing oncological and gynecological surgeries. METHODS This retrospective cohort study analyzed American College of Surgeons, National Surgical Quality Improvement Program data from adult female patients undergoing mastectomy procedures without reconstruction between 2017 and 2022. Patients were selected based on Current-Procedural-Terminology codes, excluding incomplete or non-breast-related cases. Preoperative, perioperative, and 30-day postoperative data were analyzed using logistic and linear regression models, with the mFI-5 cutoff set at 2. RESULTS Between 2017 and 2022, 860 patients underwent mastectomies at Yale Healthcare Network; 19% (n = 163) had mFI score ≥2. High-risk patients (mFI ≥2) were significantly older (66.32 ± 10.83 years) and had a higher body mass index (33.69 ± 7.73, both p < 0.001). Surgical complications occurred in 11.98% of patients, with a higher rate in the high-risk group (22.7% vs. 9.5%, p < 0.001). Adjusted multivariate logistic regression showed an increased risk of complications in frail patients (aOR 2.66; [1.60-4.43], p < 0.001). Although slight reductions in hospital stay and surgery duration were observed for high-risk patients, these differences were not significant. Sensitivity analysis confirmed higher odds of complications, including acute kidney failure (odds ratio [OR] 9.01) and pneumonia (OR 4.10). CONCLUSIONS The mFI-5 is a robust tool for predicting surgical complications in patients undergoing mastectomy, particularly those with multiple comorbidities.
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Affiliation(s)
- Laetitia S Chiarella
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
- Department of Plastic Surgery, University Hospital Muenster, Muenster, Germany
| | - Lioba Huelsboemer
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
| | - Fortunay Diatta
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
| | - Felix J Klimitz
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, Plastic- and Hand Surgery, University of Heidelberg, Ludwigshafen, Germany
| | - Alexander J Kammien
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
| | - Alejandro Kochen
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
| | - Sam Boroumand
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
| | - Omar Allam
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
| | - Martin Kauke-Navarro
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA
| | - Bohdan Pomahac
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, CT, USA.
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García-Sancha N, Corchado-Cobos R, Pérez-Losada J. Understanding Susceptibility to Breast Cancer: From Risk Factors to Prevention Strategies. Int J Mol Sci 2025; 26:2993. [PMID: 40243654 PMCID: PMC11988588 DOI: 10.3390/ijms26072993] [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: 02/05/2025] [Revised: 03/23/2025] [Accepted: 03/24/2025] [Indexed: 04/18/2025] Open
Abstract
Breast cancer is the most common malignancy among women globally, with incidence rates continuing to rise. A comprehensive understanding of its risk factors and the underlying biological mechanisms that drive tumor initiation is essential for developing effective prevention strategies. This review examines key non-modifiable risk factors, such as genetic predisposition, demographic characteristics, family history, mammographic density, and reproductive milestones, as well as modifiable risk factors like exogenous hormone exposure, obesity, diet, and physical inactivity. Importantly, reproductive history plays a dual role, providing long-term protection while temporarily increasing breast cancer risk shortly after pregnancy. Current chemoprevention strategies primarily depend on selective estrogen receptor modulators (SERMs), including tamoxifen and raloxifene, which have demonstrated efficacy in reducing the incidence of estrogen receptor-positive breast cancer but remain underutilized due to adverse effects. Emerging approaches such as aromatase inhibitors, RANKL inhibitors, progesterone antagonists, PI3K inhibitors, and immunoprevention strategies show promise for expanding preventive options. Understanding the interactions between risk factors, hormonal influences, and tumorigenesis is critical for optimizing breast cancer prevention and advancing safer, more targeted chemopreventive interventions.
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Affiliation(s)
- Natalia García-Sancha
- Institute of Molecular and Cellular Biology of Cancer (IBMCC-CIC), CSIC-University of Salamanca, 37007 Salamanca, Spain; (R.C.-C.); (J.P.-L.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
| | - Roberto Corchado-Cobos
- Institute of Molecular and Cellular Biology of Cancer (IBMCC-CIC), CSIC-University of Salamanca, 37007 Salamanca, Spain; (R.C.-C.); (J.P.-L.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
| | - Jesús Pérez-Losada
- Institute of Molecular and Cellular Biology of Cancer (IBMCC-CIC), CSIC-University of Salamanca, 37007 Salamanca, Spain; (R.C.-C.); (J.P.-L.)
- Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
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Darrigues L, Gaillard T, Sabah J, Saule C, Frank S, de Pauw A, Couturaud B, Binder JP, Feron JG, Laas-Faron E, Reyal F. [Prophylactic breast surgery in high-risk breast cancer patients]. Bull Cancer 2025; 112:286-299. [PMID: 39984363 DOI: 10.1016/j.bulcan.2025.01.002] [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: 12/06/2024] [Revised: 12/22/2024] [Accepted: 01/09/2025] [Indexed: 02/23/2025]
Abstract
INTRODUCTION Breast cancer associated with pathogenic variants of BRCA1 and BRCA2 genes requires specific management. This review examines the prognostic benefits, prophylactic surgical strategies, and impact on quality of life of patients at very high risk of breast cancer. Breast surgical prophylaxis concerns women at high risk of breast cancer with a risk assessment based on their personal and family history, or by diagnosis of pathogenic variants in high-risk genes. Personalized management is based on enhanced clinical and radiological monitoring, the use of predictive tools such as BOADICEA, and surgical options such as prophylactic bilateral mastectomy, which can reduce the risk of cancer by over 90 %. Although its impact on overall survival is still debated, advances in surgical techniques have significantly improved aesthetic results and patient satisfaction, thanks to modern reconstruction methods. The surgical strategy, whether primary or secondary, must be individualized, considering the patient's history, therapeutic needs, and preferences. Mastectomy with preservation of the skin envelope, often performed in one or two stages, offers significant psychosocial benefits, although radiotherapy may increase the risk of complications. Options include immediate reconstruction, by implant or autologous technique, adapted to the patient's morphology and any adjuvant treatments. CONCLUSION Prophylactic bilateral mastectomy is an effective strategy for reducing the risk of breast cancer, particularly in patients with pathogenic BRCA gene variants. Personalized assessment, detailed information on risks and impacts, and the use of decision-support tools are essential to enable informed choices tailored to individual patient needs.
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Affiliation(s)
- Lauren Darrigues
- Institut Curie, Paris, 26, rue d'Ulm, 75005 Paris, France; Institut Godinot, Reims, 1, rue du Général-Koenig, 51100 Reims, France.
| | | | - Jonathan Sabah
- Institut Godinot, Reims, 1, rue du Général-Koenig, 51100 Reims, France
| | - Claire Saule
- Institut Curie, Paris, 26, rue d'Ulm, 75005 Paris, France
| | - Sophie Frank
- Institut Curie, Paris, 26, rue d'Ulm, 75005 Paris, France
| | | | | | | | | | | | - Fabien Reyal
- Institut Curie, Paris, 26, rue d'Ulm, 75005 Paris, France; Institut Godinot, Reims, 1, rue du Général-Koenig, 51100 Reims, France
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6
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Roth S, Owczarzak J, Baker K, Davidson H, Jamal L. Experiences of hereditary cancer care among transgender and gender diverse people: "It's gender. It's cancer risk…it's everything". J Genet Couns 2025; 34:e1867. [PMID: 38342966 PMCID: PMC11316848 DOI: 10.1002/jgc4.1867] [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: 06/26/2023] [Revised: 12/15/2023] [Accepted: 12/27/2023] [Indexed: 02/13/2024]
Abstract
Transgender and gender diverse (TGD) individuals are a significant yet underrepresented population within genetic counseling research and broader LGBTQI+ health studies. This underrepresentation perpetuates a cycle of exclusion from the production of medical knowledge, impacting the quality and equity of care received by TGD individuals. This issue is particularly poignant in cancer genetic counseling, where TGD individuals with elevated cancer risk receive risk assessment, counseling, and referral to support based on risk figures and standards of care developed for cisgender individuals. The experiences of TGD individuals navigating inherited cancer syndromes remain largely undocumented in medical literature, posing challenges to the provision of inclusive care by genetics providers. To bridge this knowledge gap, we conducted a cross-sectional qualitative study. Nineteen semi-structured interviews were held with gender diverse adults having hereditary cancer syndromes, family histories of such syndromes, or personal histories of chest cancer. Our study employed thematic analysis using combined inductive and deductive methods to illuminate how hereditary cancer care intersects with participants' gender identities, gender expression, and gender-affirming care experiences. Participants reflected on care experiences that felt affirming or triggered gender dysphoria. Participants also discussed the interplay between risk-reducing mastectomy and top surgery, exploring co-emergent dynamics between cancer risk management and gender expression. Significantly, participants identified actionable strategies for healthcare providers to enhance support for gender diverse patients, including the mindful use of gendered language, collaborative decision-making, and conveying allyship. These findings offer valuable insights into tailoring genetic counseling to meet the unique needs of TGD individuals, advancing the path toward inclusive and appropriate care for LGBTQI+ individuals with hereditary cancer syndromes.
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Affiliation(s)
- Sarah Roth
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
- Center for Precision Health Research, NHGRI, NIH, Bethesda, Maryland, USA
| | - Jill Owczarzak
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Kellan Baker
- Whitman-Walker Health, Washington, District of Columbia, USA
| | - Hannah Davidson
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
- Center for Precision Health Research, NHGRI, NIH, Bethesda, Maryland, USA
| | - Leila Jamal
- Department of Bioethics, NIH, Bethesda, Maryland, USA
- Center for Cancer Research, NCI, NIH, Bethesda, Maryland, USA
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Patzelt M, Livancova T, Le Thanh X, Rosetzka K, Drozd J, Sukop A. Breast Cancer Occurrence After Risk-reducing Mastectomies in 274 Cases: A Single Center With More Than 42 Years of Experience. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2025; 13:e6526. [PMID: 39931117 PMCID: PMC11810035 DOI: 10.1097/gox.0000000000006526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2024] [Accepted: 12/17/2024] [Indexed: 02/13/2025]
Abstract
Introduction Carriers of genetic mutations with a high risk of developing breast cancer have a lifetime risk of this cancer of up to 70%. To reduce the risk, patients have the option of a risk-reducing mastectomy. There is limited data with only short follow-ups on its safety. The aim of the study was to determine the long-term incidence of breast cancer in healthy patients with no previous surgery, who underwent bilateral risk-reducing mastectomies (BRRMs). Methods We retrospectively reviewed 274 patients from our facility with no previous breast surgery, who underwent BRRM from 1981 to 2022, due to genetic mutations, a strong family history, or having very dense mammary glands. We approached these patients during their checkups, by phone call or email, and we asked them if they had developed breast cancer after their procedures. We recorded the patients' demographic factors, their genetic mutation types, and the mastectomy methods carried out. Results A total of 274 patients had BRRMs with a mean follow-up after 76 months; 208 patients had undergone nipple-sparing mastectomies, 39 patients had undergone skin-sparing mastectomies, and 27 patients had skin-reducing mastectomies. One BRCA1+ patient developed breast cancer 21 months after undergoing the risk-reducing skin-sparing mastectomy procedure. None of the patients died of breast cancer. Conclusions The incidence of breast cancer in the monitored patients is comparable to the results of the other related studies. The study result confirms that risk-reducing mastectomies reduce the risk of breast cancer in high-risk populations, regardless of the type of mastectomy performed.
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Affiliation(s)
- Matej Patzelt
- From the Department of Plastic Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Department of Plastic Surgery, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Tereza Livancova
- From the Department of Plastic Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Department of Plastic Surgery, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Xuan Le Thanh
- From the Department of Plastic Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Department of Plastic Surgery, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Kristyna Rosetzka
- From the Department of Plastic Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Department of Plastic Surgery, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Jan Drozd
- Department of General Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Department of General Surgery, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Andrej Sukop
- From the Department of Plastic Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Department of Plastic Surgery, Third Faculty of Medicine, Charles University, Prague, Czech Republic
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8
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Kim D, Ryu JM, Han SA, Kim Z, Kim SW. Pattern Anlysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers. Curr Oncol 2024; 31:6767-6777. [PMID: 39590130 PMCID: PMC11592990 DOI: 10.3390/curroncol31110499] [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: 09/14/2024] [Revised: 10/23/2024] [Accepted: 10/28/2024] [Indexed: 11/28/2024] Open
Abstract
The lifetime risk of breast and ovarian cancer increases substantially for individuals with mutations in BRCA1/2. The evidence indicates that BRCA1/2 mutation carriers benefit from early cancer detection and prevention strategies. However, data on the patterns of risk-reducing interventions are lacking. This study investigated the patterns of surveillance and risk-reducing interventions among unaffected BRCA1/2 mutation carriers. A cohort of unaffected BRCA1/2 mutation carriers was identified from the Korean Hereditary Breast cAncer (KOHBRA) study database, and a telephone survey was conducted. The survey included questions on the incidence of new cancers, patterns of cancer (breast, ovarian, prostate, other) surveillance, chemoprevention, risk-reducing surgery, and reasons for participating in risk-reducing strategies. Between November 2016 and November 2020, 192 BRCA1/2 mutation carriers were contacted, of which 83 responded. After excluding 37 responders who refused to participate, 46 participants (15 males, 31 females) were included in the analysis. The mean ± SD follow-up time was 103 ± 17 months (median 107, range 68~154), and the mean ± SD age was 31 ± 8 years. Ten BRCA1/2 mutation carriers developed breast cancer, one developed ovarian cancer, and three developed other cancers. Six BRCA1/2 mutation carriers (19.4%) underwent annual breast cancer surveillance as recommended by guidelines, while none underwent ovarian or prostate cancer surveillance. Three carriers (9.7%) used chemoprevention for breast cancer. Risk-reducing salpingo-oophorectomy was performed on only one BRCA1/2 mutation carrier. The rates of breast/ovarian cancer surveillance, chemoprevention, and risk-reducing surgery were low among unaffected Korean BRCA1/2 mutation carriers. Given this cohort's relatively high risk of developing breast cancer, strategies to encourage active participation in risk reduction are needed.
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Affiliation(s)
- Dabin Kim
- Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea;
| | - Jai Min Ryu
- Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea;
| | - Sang-Ah Han
- Department of Surgery, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea;
| | - Zisun Kim
- Department of Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea;
| | - Sung-Won Kim
- Department of Surgery, Daerim St. Mary’s Hospital, Seoul 07442, Republic of Korea
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9
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Heppell C, Malka S, Moosajee M. Incidental finding of a BRCA2 variant following whole genome sequencing to molecularly diagnose bilateral congenital cataracts. BMJ Case Rep 2024; 17:e260755. [PMID: 39395831 PMCID: PMC11474931 DOI: 10.1136/bcr-2024-260755] [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: 04/27/2024] [Accepted: 09/30/2024] [Indexed: 10/14/2024] Open
Abstract
A male patient in his 20s with a history of bilateral congenital cataracts and nystagmus presented to the genetic eye disease clinic at Moorfields Eye Hospital to enquire about genetic testing for family decision-making and access to preimplantation genetic testing. He had a history of lensectomy with best-corrected visual acuities of logMAR 0.60 and 1.00 in the right and left eye. Whole genome sequencing (WGS) was conducted, which included targeted analysis of a panel of 115 lens-related genes and incidental findings, for which patients are unable to opt-out. Genetic testing identified the causative variant c.134T>C (p.Leu45Pro) in the CRYGC gene. A pathogenic variant in BRCA2 was also identified as a secondary finding. This was unexpected given the absence of a strong family history of breast or ovarian cancer. This case illustrates the importance of genetic counselling and informing patients about the implications of incidental findings that arise from WGS.
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Affiliation(s)
- Cara Heppell
- Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Samantha Malka
- Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK
| | - Mariya Moosajee
- Genetics Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK
- Development, Ageing and Disease, UCL Institute of Ophthalmology, London, UK
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Pensabene M, Calabrese A, von Arx C, Caputo R, De Laurentiis M. Cancer genetic counselling for hereditary breast cancer in the era of precision oncology. Cancer Treat Rev 2024; 125:102702. [PMID: 38452709 DOI: 10.1016/j.ctrv.2024.102702] [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: 12/30/2023] [Revised: 02/23/2024] [Accepted: 02/25/2024] [Indexed: 03/09/2024]
Abstract
A relevant percentage of breast cancers (BCs) are tied to pathogenetic (P)/likely pathogenetic (LP) variants in predisposing genes. The knowledge of P/LP variants is an essential element in the management of BC patients since the first diagnosis because it influences surgery and subsequent oncological treatments and follow-up. Moreover, patients with metastatic BCs can benefit from personalized treatment if carriers of P/LP in BRCA1/2 genes. Multigene panels allow the identification of other predisposing genes with an impact on management. Cascade genetic testing for healthy family members allows personalized preventive strategies. Here, we review the advances and the challenges of Cancer Genetic Counseling (CGC). We focus on the area of oncology directed to hereditary BC management describing the peculiar way to lead CGC and how CGC changes over time. The authors describe the impact of genetic testing by targeted approach or universal approach on the management of BC according to the stage at diagnosis. Moreover, they describe the burden of CGC and testing and future perspectives to widely offer testing. A new perspective is needed for models of service delivery of CGC and testing, beyond formal genetic counselling. A broader genetic test can be quickly usable in clinical practice for comprehensive BC management and personalized prevention in the era of precision oncology.
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Affiliation(s)
- M Pensabene
- Clinical and Experimental Unit of Breast Cancer, National Cancer Institute, IRCCS "Fondazione G. Pascale", Naples, Italy.
| | - A Calabrese
- Clinical and Experimental Unit of Breast Cancer, National Cancer Institute, IRCCS "Fondazione G. Pascale", Naples, Italy.
| | - C von Arx
- Clinical and Experimental Unit of Breast Cancer, National Cancer Institute, IRCCS "Fondazione G. Pascale", Naples, Italy.
| | - R Caputo
- Clinical and Experimental Unit of Breast Cancer, National Cancer Institute, IRCCS "Fondazione G. Pascale", Naples, Italy.
| | - M De Laurentiis
- Clinical and Experimental Unit of Breast Cancer, National Cancer Institute, IRCCS "Fondazione G. Pascale", Naples, Italy.
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Irelli A, Patruno LV, Chiatamone Ranieri S, Di Giacomo D, Malatesta S, Alesse E, Tessitore A, Cannita K. Role of Breast Cancer Risk Estimation Models to Identify Women Eligible for Genetic Testing and Risk-Reducing Surgery. Biomedicines 2024; 12:714. [PMID: 38672070 PMCID: PMC11048717 DOI: 10.3390/biomedicines12040714] [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: 02/27/2024] [Revised: 03/17/2024] [Accepted: 03/21/2024] [Indexed: 04/28/2024] Open
Abstract
Hereditary breast and ovarian cancer (HBOC) syndrome is responsible for approximately 10% of breast cancers (BCs). The HBOC gene panel includes both high-risk genes, i.e., a four times higher risk of BC (BRCA1, BRCA2, PALB2, CDH1, PTEN, STK11 and TP53), and moderate-risk genes, i.e., a two to four times higher risk of BC (BARD1, CHEK2, RAD51C, RAD51D and ATM). Pathogenic germline variants (PGVs) in HBOC genes confer an absolute risk of BC that changes according to the gene considered. We illustrate and compare different BC risk estimation models, also describing their limitations. These models allow us to identify women eligible for genetic testing and possibly to offer surgical strategies for primary prevention, i.e., risk-reducing mastectomies and salpingo-oophorectomies.
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Affiliation(s)
- Azzurra Irelli
- Medical Oncology Unit, Department of Oncology, “Giuseppe Mazzini” Hospital, AUSL 04 Teramo, 64100 Teramo, Italy; (L.V.P.); (K.C.)
| | - Leonardo Valerio Patruno
- Medical Oncology Unit, Department of Oncology, “Giuseppe Mazzini” Hospital, AUSL 04 Teramo, 64100 Teramo, Italy; (L.V.P.); (K.C.)
| | - Sofia Chiatamone Ranieri
- Pathology Unit, Department of Services, AUSL 04 Teramo, 64100 Teramo, Italy; (S.C.R.); (D.D.G.); (S.M.)
| | - Daniela Di Giacomo
- Pathology Unit, Department of Services, AUSL 04 Teramo, 64100 Teramo, Italy; (S.C.R.); (D.D.G.); (S.M.)
| | - Sara Malatesta
- Pathology Unit, Department of Services, AUSL 04 Teramo, 64100 Teramo, Italy; (S.C.R.); (D.D.G.); (S.M.)
| | - Edoardo Alesse
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (E.A.); (A.T.)
| | - Alessandra Tessitore
- Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy; (E.A.); (A.T.)
| | - Katia Cannita
- Medical Oncology Unit, Department of Oncology, “Giuseppe Mazzini” Hospital, AUSL 04 Teramo, 64100 Teramo, Italy; (L.V.P.); (K.C.)
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12
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Ticha P, Sukop A. Patient-reported outcomes in bilateral prophylactic mastectomy with breast reconstruction: A narrative review. Breast 2024; 73:103602. [PMID: 37995427 PMCID: PMC10709055 DOI: 10.1016/j.breast.2023.103602] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 11/06/2023] [Accepted: 11/10/2023] [Indexed: 11/25/2023] Open
Abstract
In women at high risk of developing breast cancer, bilateral prophylactic mastectomy (BPM) 1 significantly reduces the risk; simultaneously, breast reconstruction preserves body integrity. Given the complex and personal nature of such surgical procedures, patient assessment of satisfaction and health-related quality of life (HRQoL) 2 is essential in evaluation of surgical outcomes. With this review, we aim to organize the current knowledge on patient-reported outcomes (PROs) 3 in bilateral prophylactic surgery. Literature search was conducted using the databases Google Scholar, PubMed, and Web of Science to address the following questions, which can help clinicians and women undergoing the procedures navigate their healthcare decision-making process: How does BPM with reconstruction influence cancer-related distress? How does the surgery impact patient satisfaction and HRQoL? How do preoperative PROs differ from postoperative outcomes? Does the type of BPM and the type of reconstruction impact patient satisfaction and HRQoL? Furthermore, we summarize available patient-reported outcome measures (PROMs) 4 that can be administered to women undergoing BPM with reconstruction. In addition, we discuss possible future directions for PRO research in prophylactic breast surgery.
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Affiliation(s)
- Pavla Ticha
- Department of Plastic Surgery, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Srobarova 50, 10034, Praha 10, Czech Republic.
| | - Andrej Sukop
- Department of Plastic Surgery, Kralovske Vinohrady University Hospital and Third Faculty of Medicine, Charles University, Srobarova 50, 10034, Praha 10, Czech Republic.
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13
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Wong SM, Apostolova C, Eisenberg E, Foulkes WD. Counselling Framework for Germline BRCA1/2 and PALB2 Carriers Considering Risk-Reducing Mastectomy. Curr Oncol 2024; 31:350-365. [PMID: 38248108 PMCID: PMC10814079 DOI: 10.3390/curroncol31010023] [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: 12/06/2023] [Revised: 12/31/2023] [Accepted: 01/05/2024] [Indexed: 01/23/2024] Open
Abstract
Female BRCA1/2 and PALB2 germline pathogenic variant carriers have an increased lifetime risk of breast cancer and may wish to consider risk-reducing mastectomy (RRM) for surgical prevention. Quantifying the residual lifetime risk and absolute benefit from RRM requires careful consideration of a patient's age, pathogenic variant, and their personal history of breast or ovarian cancer. Historically, patients have been counselled that RRM does not necessarily prolong survival relative to high-risk surveillance, although recent studies suggest a possible survival benefit of RRM in BRCA1 carriers. The uptake of RRM has increased dramatically over the last several decades yet varies according to sociodemographic factors and geographic region. The increased adoption of nipple-sparing mastectomy techniques, ability to avoid axillary staging, and availability of reconstructive options for most germline pathogenic variant carriers has helped to minimize the morbidity of RRM. Preoperative discussions should include evidence regarding postmastectomy sensation, the potential for supplemental surgery, pregnancy-related chest wall changes, and the need for continued clinical surveillance. Approaches that include sensation preservation and robotic nipple-sparing mastectomy are an area of evolving research that may be more widely adopted in the future.
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Affiliation(s)
- Stephanie M. Wong
- Department of Surgery, McGill University, Montreal, QC H3G 1A4, Canada
- Stroll Cancer Prevention Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC H3T 1E2, Canada
- Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H4A 3T2, Canada
| | - Carla Apostolova
- Department of Surgery, McGill University, Montreal, QC H3G 1A4, Canada
- Stroll Cancer Prevention Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC H3T 1E2, Canada
| | - Elisheva Eisenberg
- Department of Surgery, McGill University, Montreal, QC H3G 1A4, Canada
- Stroll Cancer Prevention Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC H3T 1E2, Canada
| | - William D. Foulkes
- Stroll Cancer Prevention Centre, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC H3T 1E2, Canada
- Gerald Bronfman Department of Oncology, McGill University, Montreal, QC H4A 3T2, Canada
- Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada
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14
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Li PC, Zhu YF, Cao WM, Li B. ER-positive and BRCA2-mutated breast cancer: a literature review. Eur J Med Res 2024; 29:30. [PMID: 38184581 PMCID: PMC10770892 DOI: 10.1186/s40001-023-01618-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 12/24/2023] [Indexed: 01/08/2024] Open
Abstract
BRCA2-mutated carriers have a high lifetime risk of breast cancer (BC), an early age of onset, and an increased risk of other cancers (including ovarian, pancreatic, and prostate cancer). Almost 70-80% of BRCA2-mutated BC are estrogen receptor (ER)-positive, which is a particular type of ER-positive BC that differs from sporadic ER-positive BC. This article reviews the clinicopathological features, treatment, and prognosis of ER-positive and BRCA2-mutated BC to provide a reference for clinical decision-making.
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Affiliation(s)
- Pu-Chun Li
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310022, China
- Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Yi-Fan Zhu
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310022, China
- Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China
| | - Wen-Ming Cao
- Department of Breast Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
| | - Bei Li
- Department of Geriatric, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, 310006, China.
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15
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Albujja MH, Al-Ghedan M, Dakshnamoorthy L, Pla Victori J. Preimplantation genetic testing for embryos predisposed to hereditary cancer: Possibilities and challenges. CANCER PATHOGENESIS AND THERAPY 2024; 2:1-14. [PMID: 38328708 PMCID: PMC10846329 DOI: 10.1016/j.cpt.2023.05.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Revised: 05/03/2023] [Accepted: 05/14/2023] [Indexed: 02/09/2024]
Abstract
Preimplantation genetic testing (PGT), which was developed as an alternative to prenatal genetic testing, allows couples to avoid pregnancies with abnormal chromosomes and the subsequent termination of the affected fetus. Originally used for early onset monogenic conditions, PGT is now used to prevent various types of inherited cancer conditions based on the development of PGT technology, assisted reproductive techniques (ARTs), and in vitro fertilization (IVF). This review provides insights into the potential benefits and challenges associated with the application of PGT for hereditary cancer and provides an overview of the existing literature on this test, with a particular focus on the current challenges related to laws, ethics, counseling, and technology. Additionally, this review predicts the future potential applications of this method. Although PGT may be utilized to predict and prevent hereditary cancer, each case should be comprehensively evaluated. The motives of couples must be assessed to prevent the misuse of this technique for eugenic purposes, and non-pathogenic phenotypes must be carefully evaluated. Pathological cases that require this technology should also be carefully considered based on legal and ethical reasoning. PGT may be the preferred treatment for hereditary cancer cases; however, such cases require careful case-by-case evaluations. Therefore, this study concludes that multidisciplinary counseling and support for patients and their families are essential to ensure that PGT is a viable option that meets all legal and ethical concerns.
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Affiliation(s)
- Mohammed H. Albujja
- Department of Forensic Sciences, Naif Arab University for Security Sciences, Riyadh 11452, Saudi Arabia
| | - Maher Al-Ghedan
- Genetics Laboratory, Thuriah Medical Center, Riyadh 11523, Saudi Arabia
| | | | - Josep Pla Victori
- Department of Genetic Counselling, VI-RMA Global, Valencia 46004, Spain
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16
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Bhardwaj PV, Gupta S, Elyash A, Teplinsky E. Male Breast Cancer: a Review on Diagnosis, Treatment, and Survivorship. Curr Oncol Rep 2024; 26:34-45. [PMID: 38224426 DOI: 10.1007/s11912-023-01489-z] [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] [Accepted: 12/11/2023] [Indexed: 01/16/2024]
Abstract
PURPOSE OF REVIEW Male breast cancer is a relatively uncommon and rare disease that is often managed based on evidence adopted from trials pertaining to female breast cancer due to low accrual rates or exclusion of males. This is despite the known differences in the biology and epidemiology of this condition. This review provides an update regarding the management and surveillance of male breast cancer. RECENT FINDINGS Men with breast cancer tend to undergo more extensive surgery in the breast and axilla. The outcomes of male breast cancer compared to a similar subtype of female breast cancer appear worse when matched for stage. Systemic therapies remain predominantly based on recommendations for female breast cancer, although tamoxifen is the more optimal endocrine therapy for men than women. Surveillance with mammograms is recommended for patients harboring a breast cancer susceptibility gene but is otherwise not advised for men who have undergone a mastectomy. Notably, the role of other imaging modalities, including ultrasound and magnetic resonance imaging, is minimal. Although the focus on survivorship care among men is low, it is abundantly clear that this is a stigmatizing diagnosis for men, and they suffer from long-term physical and psychological sequelae following a diagnosis and treatment of breast cancer. In summary, providing more gender-inclusive care and advocating for increased representation of men in prospective breast cancer studies and clinical trials may help improve outcomes and provide enhanced support for this population.
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Affiliation(s)
- Prarthna V Bhardwaj
- Division of Hematology-Oncology, University of Massachusetts Chan School of Medicine, Baystate, MA, USA
| | - Shilpi Gupta
- Division of Medical Oncology, Atlantic Health System, Morristown Medical Center, Morristown, NJ, USA
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17
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Boyd CJ, Ramesh S, Bekisz JM, Guth AA, Axelrod DM, Shapiro RL, Hiotis K, Schnabel FR, Karp NS, Choi M. Low Cancer Occurrence Rate following Prophylactic Nipple-Sparing Mastectomy. Plast Reconstr Surg 2024; 153:37e-43e. [PMID: 36999997 DOI: 10.1097/prs.0000000000010481] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/01/2023]
Abstract
BACKGROUND Nipple-sparing mastectomy (NSM) has become widely available for breast cancer prophylaxis. There are limited data on its long-term oncologic safety. The objective of this study was to determine the incidence of breast cancer in patients who underwent prophylactic NSM. METHODS All patients undergoing prophylactic NSM at a single institution from 2006 through 2019 were retrospectively reviewed. Patient demographic factors, genetic predispositions, mastectomy specimen pathology, and oncologic occurrences at follow-up were recorded. Descriptive statistics were performed where necessary to classify demographic factors and oncologic characteristics. RESULTS A total of 871 prophylactic NSMs were performed on 641 patients, with median follow-up of 82.0 months (standard error 1.24). A total of 94.4% of patients ( n = 605) underwent bilateral NSMs, although only the prophylactic mastectomy was considered. The majority of mastectomy specimens (69.6%) had no identifiable pathology. A total of 38 specimens (4.4%) had cancer identified in mastectomy specimens, with ductal carcinoma in situ being the most common (92.1%; n = 35). Multifocal or multicentric disease was observed in seven cases (18.4%) and lymphovascular invasion was identified in two (5.3%). One patient (0.16%), who was a BRCA2 variant carrier, was found to have breast cancer 6.5 years after prophylactic mastectomy. CONCLUSIONS Overall primary oncologic occurrence rates are very low in high-risk patients undergoing prophylactic NSM. In addition to reducing the risk of oncologic occurrence, prophylactic surgery itself may be therapeutic in a small proportion of patients. Continued surveillance for these patients remains important to assess at longer follow-up intervals. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, IV.
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Affiliation(s)
- Carter J Boyd
- From the Hansjörg Wyss Department of Plastic Surgery
| | - Sruthi Ramesh
- From the Hansjörg Wyss Department of Plastic Surgery
| | | | - Amber A Guth
- Division of Surgical Oncology, Department of Surgery, New York University Langone Health
| | - Deborah M Axelrod
- Division of Surgical Oncology, Department of Surgery, New York University Langone Health
| | - Richard L Shapiro
- Division of Surgical Oncology, Department of Surgery, New York University Langone Health
| | - Karen Hiotis
- Division of Surgical Oncology, Department of Surgery, New York University Langone Health
| | - Freya R Schnabel
- Division of Surgical Oncology, Department of Surgery, New York University Langone Health
| | - Nolan S Karp
- From the Hansjörg Wyss Department of Plastic Surgery
| | - Mihye Choi
- From the Hansjörg Wyss Department of Plastic Surgery
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18
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Liu T, Yu J, Gao Y, Ma X, Jiang S, Gu Y, Ming WK. Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers. Cancers (Basel) 2023; 16:103. [PMID: 38201529 PMCID: PMC10778044 DOI: 10.3390/cancers16010103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/16/2023] [Accepted: 12/21/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions. However, a meta-analysis of their efficacy and the impact of different genetic variants on their effectiveness is lacking. METHODS A systematic review and meta-analysis were conducted, adhering to Cochrane guidelines. The review encompassed studies that involved prophylactic interventions for healthy women with BRCA variants, focusing on cancer incidence and mortality outcomes. The Newcastle-Ottawa Scale was used for risk of bias assessment. We pooled the extracted outcomes using random effects models and conducted subgroup analyses stratified by intervention, variant, and cancer types. RESULTS A total of 21 studies met the inclusion criteria. The meta-analysis revealed that prophylactic interventions significantly reduced cancer risk and mortality. The subgroup analysis showed a greater protective effect for BRCA2 than BRCA1 variant carriers. Risk-reducing surgeries (RRS) were more effective than chemoprevention, with RRS notably reducing cancer risk by 56% compared to 39% for chemoprevention. Prophylactic oophorectomy significantly reduced HBOC risks, while the effect of prophylactic mastectomy and chemoprevention on mortality was less conclusive. CONCLUSIONS Prophylactic interventions significantly reduce the risk of HBOC and associated mortality. This comprehensive analysis provides insights for future economic evaluations and clinical decision-making in HBOC interventions.
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Affiliation(s)
- Taoran Liu
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
| | - Jing Yu
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
| | - Yangyang Gao
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
| | - Xinyang Ma
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
| | - Shan Jiang
- Macquarie University Centre for the Health Economy, Macquarie Business School and Australian Institute of Health Innovation, Macquarie University, Sydney, NSW 2109, Australia
| | - Yuanyuan Gu
- Macquarie University Centre for the Health Economy, Macquarie Business School and Australian Institute of Health Innovation, Macquarie University, Sydney, NSW 2109, Australia
| | - Wai-kit Ming
- Department of Infectious Diseases and Public Health, City University of Hong Kong, Hong Kong 999077, China
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19
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Hallsson LR, Sroczynski G, Engel J, Siebert U. Decision-analytic evaluation of the comparative effectiveness and cost-effectiveness of strategies to prevent breast and ovarian cancer in German women with BRCA-1/2 mutations. BMC Cancer 2023; 23:590. [PMID: 37365514 PMCID: PMC10294312 DOI: 10.1186/s12885-023-10956-6] [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: 11/23/2022] [Accepted: 05/13/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND Women with inherited mutations in the BRCA1 or BRCA2 genes have increased lifetime risks for developing breast and/or ovarian cancer and may develop these cancers around the age of 30 years. Therefore, prevention of breast and ovarian cancer in these women may need to start relatively early in life. In this study we systematically evaluate the long-term effectiveness and cost effectiveness of different prevention strategies for breast and ovarian cancer in women with BRCA-1/2 mutation in Germany. METHODS A decision-analytic Markov model simulating lifetime breast and ovarian cancer development in BRCA-1/2 carriers was developed. Different strategies including intensified surveillance (IS), prophylactic bilateral mastectomy (PBM), and prophylactic bilateral salpingo-oophorectomy (PBSO) alone or in combination at different ages were evaluated. German clinical, epidemiological, and economic (in 2022 Euro) data were used. Outcomes included cancer incidences, mortality, life years (LYs), quality-adjusted life years (QALYs), and discounted incremental cost-effectiveness ratios (ICER). We adopted the German health-care system perspective and discounted costs and health effects with 3% annually. RESULTS All intervention strategies are more effective and less costly than IS alone. Prevention with PBM plus PBSO at age 30 maximizes life expectancy with 6.3 LYs gained, whereas PBM at age 30 with delayed PBSO at age 35 improves quality of life with 11.1 QALYs gained, when compared to IS alone. A further delay of PBSO was associated with lower effectiveness. Both strategies are cost effective with ICERs significantly below 10,000 EUR/LYG or QALY. CONCLUSION Based on our results, PBM at age 30 plus PBSO between age 30 and 40 prolongs life and is cost effective in women with BRCA-1/2 mutations in Germany. Serial preventive surgeries with delayed PBSO potentially improve quality of life for women. However, delaying PBM and/or PBSO further may lead to increased mortality and reduced QALYs.
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Affiliation(s)
- Lára R Hallsson
- Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL - University for Health Sciences and Technology, Eduard-Wallnoefer-Zentrum 1, Hall in Tirol, A-6060, Austria
- Division of Health Technology Assessment and Bioinformatics, ONCOTYROL - Center for Personalized Cancer Medicine, Innsbruck, Austria
- IBE-Institute for Medical Informatics, Biometry and Epidemiology, LMU-Ludwig-Maximilians- University, Munich, Germany
| | - Gaby Sroczynski
- Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL - University for Health Sciences and Technology, Eduard-Wallnoefer-Zentrum 1, Hall in Tirol, A-6060, Austria
| | - Jutta Engel
- MCR-Munich Cancer Registry, Institute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians Universität (LMU), Munich, Germany
| | - Uwe Siebert
- Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and Health Technology Assessment, UMIT TIROL - University for Health Sciences and Technology, Eduard-Wallnoefer-Zentrum 1, Hall in Tirol, A-6060, Austria.
- Division of Health Technology Assessment and Bioinformatics, ONCOTYROL - Center for Personalized Cancer Medicine, Innsbruck, Austria.
- Center for Health Decision Science, Departments of Epidemiology and Health Policy & Management, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
- Institute for Technology Assessment, Department of Radiology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
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20
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Stadler ZK, Schrag D. Genetic Testing for Cancer Susceptibility. JAMA 2023:2805797. [PMID: 37276548 DOI: 10.1001/jama.2023.9474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Affiliation(s)
- Zsofia K Stadler
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Deborah Schrag
- Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Associate Editor, JAMA
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21
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Manley K, Ryan N, Jenner A, Newton C, Hillard T. Counselling of path_ BRCA carriers who are considering risk-reducing oophorectomy. Post Reprod Health 2023; 29:42-52. [PMID: 36757900 DOI: 10.1177/20533691231156640] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2023]
Abstract
path_BRCA 1/2 increases a woman's lifetime risk of breast and ovarian cancer. Interventions can be offered which manage cancer risk; annual breast screening from age 30, chemoprevention and, once a woman's family is complete, risk-reducing surgery. The latter is the most effective method of reducing cancer in path_BRCA carriers; salpingo-oophorectomy reduces breast and ovarian cancer, respectively, by up to 50% and 95%. Factors affecting a woman's decision to undergo risk-reducing surgery are complex; dominant factors include risks of surgery, effect on cancer outcomes and menopausal sequelae. Specific information relating to hormone replacement and non-hormonal alternatives are an important consideration for women but, are often overlooked. Informative counselling is required to enable satisfaction with the chosen intervention whilst improving survival outcomes. This review paper outlines the current data pertaining to these decision-making factors and provides a proforma to enable effective counselling.
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Affiliation(s)
- Kristyn Manley
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
| | - Neil Ryan
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
- Department of Gynaecology Oncology, Royal Infirmary of Edinburgh, Edinburgh
| | - Abigail Jenner
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- Department of Oncology, 1556Royal United Hospitals Bath, Bath, UK
| | - Claire Newton
- Department of Gynaecology, 1984University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UK
- The Academic Women's Health Unit, Translational Women's Health Sciences, 152004University of Bristol, Bristol, UK
| | - Timothy Hillard
- Department of Gynaecology, 6655University Hospitals Dorset, Poole, UK
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22
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Clarijs ME, van Egdom LSE, Verhoef C, Vasilic D, Koppert LB. Bilateral prophylactic mastectomy: should we preserve the pectoral fascia? Protocol of a Dutch double blinded, prospective, randomised controlled pilot study with a within-subject design (PROFAS). BMJ Open 2023; 13:e066728. [PMID: 36806067 PMCID: PMC9944307 DOI: 10.1136/bmjopen-2022-066728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/19/2023] Open
Abstract
INTRODUCTION Bilateral prophylactic mastectomy (BPM) in women with a high risk of developing breast cancer has shown to provide the greatest risk reduction. Many surgical guidelines recommend the removal of the pectoral fascia (PF) in mastectomies; however, there is no evidence to support this statement. Reported wound-related complications following mastectomy include seroma, flap necrosis, infection and haematoma. Seroma causes discomfort and may delay the reconstructive procedures. Whether removal or preservation of the PF influences drain volume, seroma formation and other postoperative complications following BPM remains unclear. The aim of this study is to assess the impact of removal versus preservation of the PF on drain policy and seroma after BPM. METHODS AND ANALYSIS This is a double blinded, prospective, randomised controlled pilot study with a within-subject design. The inclusion criteria are women >18 years, presenting in the Academic Breast Cancer Centre Rotterdam, who are opting for BPM. Patients with a history or diagnosis of breast cancer are excluded. According to the sample size calculation based on the difference in total drain volume, a number of 21 eligible patients will be included. Randomisation will occur within the patient, which means PF preservation in one breast and PF removal in the contralateral breast. The primary study endpoint is total drainage volume. Secondary study outcomes include time to drain removal, number of needle aspirations, postoperative complications and length of hospital stay. ETHICS AND DISSEMINATION The study is approved by the Erasmus Medical Center Review Board (REC 2020-0431). Results will be presented during international conferences and published in a peer-reviewed academic journal. TRIAL REGISTRATION NUMBER NCT05391763; clinicaltrials.gov.
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Affiliation(s)
- Marloes E Clarijs
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, Zuid-Holland, The Netherlands
| | - Laurentine S E van Egdom
- Department of Plastic and Reconstructive Surgery, Erasmus Medical Center, Rotterdam, Zuid-Holland, The Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, Zuid-Holland, The Netherlands
| | - Dalibor Vasilic
- Department of Plastic and Reconstructive Surgery, Erasmus Medical Center, Rotterdam, Zuid-Holland, The Netherlands
| | - Linetta B Koppert
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, Rotterdam, Zuid-Holland, The Netherlands
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23
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Robson M. Testing for Inherited Susceptibility to Breast Cancer. Hematol Oncol Clin North Am 2023; 37:17-31. [PMID: 36435609 DOI: 10.1016/j.hoc.2022.08.003] [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: 11/24/2022]
Abstract
When BRCA1 and BRCA2 were first identified, the initial models for delivering testing were shaped by concepts of genetic exceptionalism and a lack of data regarding therapeutic implications and the effectiveness of risk reduction. Since then, interventions have been effective, and treatment implications have become clear. The sensitivity of guideline-based testing is incomplete, leading to calls for universal testing. Completely universal testing, however, is not necessary to identify the great majority of BRCA1 or BRCA2 variants. Broader testing (both in terms of eligibility and genes tested) will identify more variants, particularly in moderate penetrance genes, but the clinical implications remain less clear for these variants.
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Affiliation(s)
- Mark Robson
- Breast Medicine Service, Department of Medicine, Memorial Hospital for Treatment of Cancer and Allied Disease, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 300 East 66th Street, Room 813, New York, NY 10065, USA.
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24
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Psychological factors and the uptake of preventative measures in BRCA1/2 pathogenic variant carriers: results of a prospective cohort study. Hered Cancer Clin Pract 2022; 20:38. [PMID: 36536421 PMCID: PMC9761978 DOI: 10.1186/s13053-022-00244-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 11/23/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Women carrying BRCA1/2 pathogenic variants are exposed to elevated risks of developing breast cancer (BC) and are faced by a complex decision-making process on preventative measures, i.e., risk-reducing mastectomy (RRM), and intensified breast surveillance (IBS). In this prospective cohort study we investigated the effect of anxiety, personality factors and coping styles on the decision-making process on risk management options in women with pathogenic variants in BRCA1/2. METHODS Breast cancer unaffected and affected women with a pathogenic variant in the BRCA1 or BRCA2 gene were psychologically evaluated immediately before (T0), 6 to 8 weeks (T1) and 6 to 8 months (T2) after the disclosure of their genetic test results. Uptake of RRM and IBS was assessed at T2. Psychological data were gathered using questionnaires on risk perception, personality factors, coping styles, decisional conflict, depression and anxiety, including the Hospital Anxiety and Depression Scale (HADS). We performed tests on statistical significance and fitted a logistic regression based on significance level. RESULTS A total of 98 women were included in the analysis. Baseline anxiety levels in women opting for RRM were high but decreased over time, while they increased in women opting for intensified breast surveillance (IBS). Elevated levels of anxiety after genetic test result disclosure (T1) were associated with the decision to undergo RRM (p < 0.01; OR = 1.2, 95% CI = 1.05-1.42), while personal BC history and personality factors seemed to be less relevant. CONCLUSIONS Considering psychosocial factors influencing the decision-making process of women with pathogenic variants in BRCA1/2 may help improving their genetic and psychological counselling. When opting for IBS they may profit from additional medical and psychological counselling. TRIAL REGISTRATION Retrospectively registered at the German Clinical Trials Register under DRKS00027566 on January 13, 2022.
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Saccardi C, Spagnol G, Saibene T, De Lorenzo LS, Marchetti M, Bonaldo G, Michieletto S, Toffanin MC, Noventa M, Tozzi R. Risk-Reducing Salpingo-Oophorectomy (RRSO) Combined with Simultaneous Mastectomy in Women with BRCA 1-2 Mutation Carriers: The Surgical Technique, the Feasibility and Patients' Satisfaction of Multiple Surgeries. J Clin Med 2022; 11:jcm11247502. [PMID: 36556118 PMCID: PMC9782152 DOI: 10.3390/jcm11247502] [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: 11/20/2022] [Revised: 12/05/2022] [Accepted: 12/13/2022] [Indexed: 12/23/2022] Open
Abstract
The main goal of our study was to evaluate the surgical technique, the feasibility and patient's satisfaction of multiple surgeries: Risk-reducing salpingo-oophorectomy (RRSO) combined with mastectomy in patients with BRCA 1-2 mutation carriers. We conducted a retrospective analysis of patients with BRCA 1-2 variants who underwent RRSO combined with risk-reducing bilateral mastectomy (RRBM) or surgeries for breast cancer from January-2015 to December-2021. We collected data about surgeries, complications, and patients' satisfaction using a questionnaire submitted 30 days after surgery. We included 54 patients. Forty-eight patients underwent RRSO, and six patients underwent RRSO + Total laparoscopic hysterectomy (LTH). The minor postoperative complications within 30 days were four: one breast seromas aspiration (1.9%), one infectious reconstructive complication treated with antibiotics therapy (1.9%), one Red-Breast-Syndrome (1.9%) and one trocar abdominal hematoma (1.9%) associated with RRSO. The major postoperative complications within 30 days were five: two evacuations of a breast hematoma (3.7%) and three infectious reconstructive complications treated with removal expander/implant (5.6%). No postoperative complications after 30 days were observed. According to the satisfaction questionnaire, more than 90% of patients were satisfied and would have combined surgery again. In conclusion, the multiple surgeries seem feasible and safety with a single anesthesia, a single surgical time, a single postoperative recovery, and a high patients' satisfactions without increasing morbidity.
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Affiliation(s)
- Carlo Saccardi
- Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35100 Padua, Italy
| | - Giulia Spagnol
- Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35100 Padua, Italy
- Correspondence:
| | - Tania Saibene
- Breast Surgery Unit, Veneto Institute of Oncology IOV—IRCCS, 35100 Padua, Italy
| | - Luciana Serena De Lorenzo
- Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35100 Padua, Italy
| | - Matteo Marchetti
- Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35100 Padua, Italy
| | - Giulio Bonaldo
- Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35100 Padua, Italy
| | - Silvia Michieletto
- Breast Surgery Unit, Veneto Institute of Oncology IOV—IRCCS, 35100 Padua, Italy
| | | | - Marco Noventa
- Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35100 Padua, Italy
| | - Roberto Tozzi
- Department of Women and Children’s Health, Clinic of Gynecology and Obstetrics, University of Padua, 35100 Padua, Italy
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Bernstein-Molho R, Friedman E, Evron E. Controversies and Open Questions in Management of Cancer-Free Carriers of Germline Pathogenic Variants in BRCA1/BRCA2. Cancers (Basel) 2022; 14:cancers14194592. [PMID: 36230512 PMCID: PMC9559251 DOI: 10.3390/cancers14194592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/06/2022] [Accepted: 09/19/2022] [Indexed: 11/16/2022] Open
Abstract
Females harboring germline BRCA1/BRCA2 (BRCA) P/LPV are offered a tight surveillance scheme from the age of 25−30 years, aimed at early detection of specific cancer types, in addition to risk-reducing strategies. Multiple national and international surveillance guidelines have been published and updated over the last two decades from geographically diverse countries. We searched for guidelines published between 1 January 2015 and 1 May 2022. Differences between guidelines on issues such as primary prevention, mammography screening in young (<30 years) carriers, MRI screening in carriers above age 65 years, breast imaging (if any) after risk-reducing bilateral mastectomy, during pregnancy, and breastfeeding, and hormone-replacement therapy, are just a few notable examples. Beyond formal guidelines, BRCA carriers’ concerns also focus on the timing of risk-reducing surgeries, fertility preservation, management of menopausal symptoms in cancer survivors, and pancreatic cancer surveillance, issues that, for some, there are no data to support evidence-based recommendations. This review discusses these unsettled issues, emphasizing the importance of future studies to enable global guideline harmonization for optimal surveillance strategies. Moreover, it raises the unmet need for personalized risk stratification and surveillance in BRCA P/LPV carriers.
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Affiliation(s)
- Rinat Bernstein-Molho
- The Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 5265601, Israel
| | - Eitan Friedman
- Assuta Medical Center, Tel-Aviv, Israel, The Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 8436322, Israel
| | - Ella Evron
- Oncology, Kaplan Medical Institute, Rehovot, Hadassah Medical School, The Hebrew University, Jerusalem 9190501, Israel
- Correspondence: or ; Tel.: +972-502-056-171
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Aristei C, Bölükbaşı Y, Kaidar-Person O, Pfeffer R, Arenas M, Boersma LJ, Ciabattoni A, Coles CE, Franco P, Krengli M, Leonardi MC, Marazzi F, Masiello V, Meattini I, Montero A, Offersen B, Trigo ML, Bourgier C, Genovesi D, Kouloulias V, Morganti AG, Meduri B, Pasinetti N, Pedretti S, Perrucci E, Rivera S, Tombolini V, Vidali C, Valentini V, Poortmans P. Ways to improve breast cancer patients' management and clinical outcome: The 2020 Assisi Think Tank Meeting. Crit Rev Oncol Hematol 2022; 177:103774. [PMID: 35917884 DOI: 10.1016/j.critrevonc.2022.103774] [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: 06/08/2021] [Revised: 07/19/2022] [Accepted: 07/29/2022] [Indexed: 10/16/2022] Open
Abstract
We report on the third Assisi Think Tank Meeting (ATTM) on breast cancer, a brainstorming project which involved European radiation and clinical oncologists who were dedicated to breast cancer research and treatment. Held on February 2020, the ATTM aimed at identifying key clinical questions in current clinical practice and "grey" areas requiring research to improve management and outcomes. Before the meeting, three key topics were selected: 1) managing patients with frailty due to either age and/or multi-morbidity; 2) stereotactic radiation therapy and systemic therapy in the management of oligometastatic disease; 3) contralateral breast tumour prevention in BCRA-mutated patients. Clinical practice in these areas was investigated by means of an online questionnaire. In the lapse period between the survey and the meeting, the working groups reviewed data, on-going studies and the clinical challenges which were then discussed in-depth and subjected to intense brainstorming during the meeting; research protocols were also proposed. Methodology, outcome of discussions, conclusions and study proposals are summarized in the present paper. In conclusion, this report presents an in-depth analysis of the state of the art, grey areas and controversies in breast cancer radiation therapy and discusses how to confront them in the absence of evidence-based data to guide clinical decision-making.
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Affiliation(s)
- Cynthia Aristei
- Radiation Oncology Section, Department of Medicine and Surgery, University of Perugia and Perugia General Hospital, Perugia, Italy.
| | - Yasemin Bölükbaşı
- Radiation Oncology Acıbadem Mehmet Ali Aydınlar University School of Medicine, Istanbul, Turkey
| | - Orit Kaidar-Person
- Breast Radiation Unit, Radiation Oncology, Sheba Medical Center, Ramat Gan, Israel
| | - Raphael Pfeffer
- Oncology Institute, Assuta Medical Center, Tel Aviv and Ben Gurion University Medical School, Israel
| | - Meritxell Arenas
- Universitat Rovira I Virgili, Radiation Oncology Department, Hospital Universitari Sant Hoan de Reus, IISPV, Spain
| | - Liesbeth J Boersma
- Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands
| | - Antonella Ciabattoni
- Department of Radiation Oncology, San Filippo Neri Hospital, ASL Rome 1, Rome, Italy
| | | | - Pierfrancesco Franco
- Depatment of Translational Medicine, University of Eastern Piedmont and Department of Radiation Oncology, 'Maggiore della Carità' University Hospital, Novara, Italy
| | - Marco Krengli
- Depatment of Translational Medicine, University of Eastern Piedmont and Department of Radiation Oncology, 'Maggiore della Carità' University Hospital, Novara, Italy
| | | | - Fabio Marazzi
- Unità Operativa di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagine, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Gemelli IRCSS Roma, Italy
| | - Valeria Masiello
- Unità Operativa di Radioterapia Oncologica, Dipartimento di Diagnostica per Immagine, Radioterapia Oncologica ed Ematologia, Fondazione Policlinico Gemelli IRCSS Roma, Italy
| | - Icro Meattini
- Department of Experimental and Clinical Biomedical Sciences "M. Serio", University of Florence & Radiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy
| | - Angel Montero
- Department of Radiation Oncology, University Hospital HM Sanchinarro, HM Hospitales, Madrid, Spain
| | - Birgitte Offersen
- Department of Experimental Clinical Oncology, Department of Oncology, Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark
| | - Maria Lurdes Trigo
- Service of Brachytherapy, Department of Image and Radioncology, Instituto Português Oncologia Porto Francisco Gentil E.P.E., Portugal
| | - Céline Bourgier
- Radiation Oncology, ICM-Val d'Aurelle, Univ Montpellier, Montpellier, France
| | - Domenico Genovesi
- Radiation Oncology, Ospedale Clinicizzato Chieti and University "G. d'Annunzio", Chieti, Italy
| | - Vassilis Kouloulias
- 2(nd) Department of Radiology, Radiotherapy Unit, Medical School, National and Kapodistrian University of Athens, Greece
| | - Alessio G Morganti
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna; DIMES, Alma Mater Studiorum Bologna University; Bologna, Italy
| | - Bruno Meduri
- Radiation Oncology Unit, University Hospital of Modena, Modena, Italy
| | - Nadia Pasinetti
- Radiation Oncology Service, ASST Valcamonica Esine and Brescia University, Brescia, Italy
| | - Sara Pedretti
- Istituto del Radio "O.Alberti" - Spedali Civili Hospital and Brescia University, Brescia
| | | | - Sofia Rivera
- Radiation Oncology, Institut Gustave Roussy, Villejuif, France
| | - Vincenzo Tombolini
- Radiation Oncology, Department of Radiological, Oncological and Pathological Science, University "La Sapienza", Roma, Italy
| | - Cristiana Vidali
- former Senior Assistant Department of Radiation Oncology, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy
| | - Vincenzo Valentini
- Division of Radiation Oncology, IEO European Institute of Oncology, IRCCS, Milan, Italy
| | - Philip Poortmans
- Department of Radiation Oncology, Iridium Kankernetwerk, Antwerp, Belgium; University of Antwerp, Faculty of Medicine and Health Sciences, Antwerp, Belgium
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Satisfaction with Long-Term Aesthetic and 10 Years Oncologic Outcome following Risk-Reducing Mastectomy and Implant-Based Breast Reconstruction with or without Nipple Preservation. Cancers (Basel) 2022; 14:cancers14153607. [PMID: 35892866 PMCID: PMC9331253 DOI: 10.3390/cancers14153607] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 07/09/2022] [Accepted: 07/16/2022] [Indexed: 11/17/2022] Open
Abstract
Incidence of bilateral risk-reducing mastectomies (RRMs) is increasing. The aim of this study was to compare satisfaction, aesthetic and oncological outcomes in women undergoing RRM with implant-based reconstruction comparing nipple-sparing mastectomy (NSM) with skin-sparing mastectomy (SSM) (sacrificing the nipple +/− nipple reconstruction). Women who had undergone bilateral RRM between 1997 and 2016 were invited. Aesthetic outcome and nipple symmetry were evaluated using standardized anthropometric measurements. The oncological outcome was assessed at last documented follow up. Ninety-three women (186 breasts) participated, 60 (64.5%) had NSM, 33 (35.5%) SSM. Median time between surgery and participation was 98.4 months (IQR: 61.7−133.9). Of the women, 23/33 (69.7%) who had SSM underwent nipple reconstruction. Nipple projection was shorter in the reconstructed SSM group than the maintained NSM group (p < 0.001). There was no significant difference in overall symmetry (p = 0.670), satisfaction regarding nipple preservation (p = 0.257) or overall nipple satisfaction (p = 0.074). There were no diagnoses of breast cancer at a median follow up of 129 months (IQR: 65−160.6). Women who undergo nipple-sparing RRM maintain long-term nipple symmetry. Nipple projection was less maintained after nipple reconstruction. Although satisfaction with the nipples was higher in the NSM group, this did not reach statistical significance. No breast cancers developed after RRM with long-term follow up.
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Shalabi SF, LaBarge MA. Cellular and molecular mechanisms of breast cancer susceptibility. Clin Sci (Lond) 2022; 136:1025-1043. [PMID: 35786748 DOI: 10.1042/cs20211158] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 06/16/2022] [Accepted: 06/22/2022] [Indexed: 11/17/2022]
Abstract
There is a plethora of recognized risk factors for breast cancer (BC) with poorly understood or speculative biological mechanisms. The lack of prevention options highlights the importance of understanding the mechanistic basis of cancer susceptibility and finding new targets for breast cancer prevention. Until now, we have understood risk and cancer susceptibility primarily through the application of epidemiology and assessing outcomes in large human cohorts. Relative risks are assigned to various human behaviors and conditions, but in general the associations are weak and there is little understanding of mechanism. Aging is by far the greatest risk factor for BC, and there are specific forms of inherited genetic risk that are well-understood to cause BC. We propose that bringing focus to the biology underlying these forms of risk will illuminate biological mechanisms of BC susceptibility.
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Affiliation(s)
- Sundus F Shalabi
- Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Medical Research Center, Al-Quds University, Jerusalem, Palestine
| | - Mark A LaBarge
- Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Center for Cancer and Aging, Beckman Research Institute, City of Hope, Duarte, CA, U.S.A
- Center for Cancer Biomarkers Research (CCBIO), Bergen, Norway
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Kufel-Grabowska J, Podolak A, Maliszewski D, Bartoszkiewicz M, Ramlau R, Lukaszuk K. Fertility Counseling in BRCA1/2-Mutated Women with Breast Cancer and Healthy Individuals. J Clin Med 2022; 11:jcm11143996. [PMID: 35887761 PMCID: PMC9321124 DOI: 10.3390/jcm11143996] [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: 05/15/2022] [Revised: 06/27/2022] [Accepted: 07/03/2022] [Indexed: 11/16/2022] Open
Abstract
Breast cancer is the most commonly diagnosed cancer worldwide and the fifth leading cause of cancer death. In 2020, there were 2.3 million new cases, and 685,000 women died from it. Breast cancer among young women under 40 years of age accounts for 5% to 10% of all cases of this cancer. The greater availability of multi-gene sequence analysis by next-generation sequencing has improved diagnosis and, consequently, the possibility of using appropriate therapeutic approaches in BRCA1/2 gene mutation carriers. Treatment of young breast cancer patients affects their reproductive potential by reducing ovarian reserve. It can lead to reversible or permanent premature menopause, decreased libido, and other symptoms of sex hormone deficiency. This requires that, in addition to oncological treatment, patients are offered genetic counseling, oncofertility, psychological assistance, and sexological counseling. Given the number of BRCA1/2 gene mutation carriers among young breast cancer patients, but also thanks to growing public awareness, among their healthy family members planning offspring, the possibility of benefiting from preimplantation testing and performing cancer-risk-reduction procedures: RRM (risk-reducing mastectomy) and RRSO (risk-reducing salpingo-oophorectomy) significantly increase the chance of a genetically burdened person living a healthy life and giving birth to a child not burdened by the parent's germline mutation. The goal of this paper is to show methods and examples of fertility counselling for BRCA1/2 gene mutation carriers, including both patients already affected by cancer and healthy individuals.
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Affiliation(s)
- Joanna Kufel-Grabowska
- Department of Oncology, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (J.K.-G.); (R.R.)
| | - Amira Podolak
- Department of Obstetrics and Gynecological Nursing, Faculty of Health Sciences, Medical University of Gdansk, 80-210 Gdansk, Poland; (A.P.); (K.L.)
| | - Daniel Maliszewski
- Department of General and Oncological Surgery, Wojewódzki Szpital Specjalistyczny im. Janusza Korczaka w Słupsku Sp. z o.o., 76-200 Słupsk, Poland;
- Department of General and Oncological Surgery at Specialist Hospital in Koscierzyn, Sp.z.o.o., 83-400 Kościerzyna, Poland
- Swissmed Health Center, 80-210 Gdansk, Poland
| | - Mikołaj Bartoszkiewicz
- Department of Immunobiology, Poznan University of Medical Sciences, 60-806 Poznan, Poland
- Correspondence: ; Tel.: +48-61-854-76-53
| | - Rodryg Ramlau
- Department of Oncology, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (J.K.-G.); (R.R.)
| | - Krzysztof Lukaszuk
- Department of Obstetrics and Gynecological Nursing, Faculty of Health Sciences, Medical University of Gdansk, 80-210 Gdansk, Poland; (A.P.); (K.L.)
- Invicta Research and Development Center, 81-740 Sopot, Poland
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Murray MF, Khoury MJ, Abul-Husn NS. Addressing the routine failure to clinically identify monogenic cases of common disease. Genome Med 2022; 14:60. [PMID: 35672798 PMCID: PMC9175445 DOI: 10.1186/s13073-022-01062-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 05/16/2022] [Indexed: 12/14/2022] Open
Abstract
Changes in medical practice are needed to improve the diagnosis of monogenic forms of selected common diseases. This article seeks to focus attention on the need for universal genetic testing in common diseases for which the recommended clinical management of patients with specific monogenic forms of disease diverges from standard management and has evidence for improved outcomes.We review evidence from genomic screening of large patient cohorts, which has confirmed that important monogenic case identification failures are commonplace in routine clinical care. These case identification failures constitute diagnostic misattributions, where the care of individuals with monogenic disease defaults to the treatment plan offered to those with polygenic or non-genetic forms of the disease.The number of identifiable and actionable monogenic forms of common diseases is increasing with time. Here, we provide six examples of common diseases for which universal genetic test implementation would drive improved care. We examine the evidence to support genetic testing for common diseases, and discuss barriers to widespread implementation. Finally, we propose recommendations for changes to genetic testing and care delivery aimed at reducing diagnostic misattributions, to serve as a starting point for further evaluation and development of evidence-based guidelines for implementation.
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Affiliation(s)
- Michael F. Murray
- grid.47100.320000000419368710Yale Center for Genomic Health, Department of Genetics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520 USA
| | - Muin J. Khoury
- grid.416738.f0000 0001 2163 0069Office of Genomics and Precision Public Health, Office of Science, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329 USA
| | - Noura S. Abul-Husn
- grid.59734.3c0000 0001 0670 2351Institute for Genomic Health, Division of Genomic Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1041, New York, NY 10029 USA
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Wong SM, Ferroum A, Apostolova C, Alhassan B, Prakash I, Basik M, Boileau JF, Meterissian S, Aleynikova O, Wong N, Foulkes WD. Incidence of Occult Breast Cancer in Carriers of BRCA1/2 or Other High-Penetrance Pathogenic Variants Undergoing Prophylactic Mastectomy: When is Sentinel Lymph Node Biopsy Indicated? Ann Surg Oncol 2022; 29:6660-6668. [PMID: 35616744 DOI: 10.1245/s10434-022-11916-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/03/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND This study sought to determine the likelihood of occult malignancy during risk-reducing mastectomy in high-penetrance pathogenic variant carriers to help refine axillary staging recommendations. METHODS The authors performed a retrospective cohort study analyzing all female carriers of pathogenic variants in BRCA1/2, PALB2 or other genes who underwent prophylactic surgery at their institution between 2006 and 2021. Occult breast cancer was defined as the unanticipated presence of in situ or invasive malignancy on pathologic evaluation of prophylactic mastectomy specimens. RESULTS Of 523 women, 243 carriers met the inclusion criteria for the study including 124 BRCA1 (51.0%), 108 BRCA2 (44.4%), and 11 PALB2, TP53, CDH1, or PTEN (4.6%) carriers. The median age was 44 years (interquartile range, 37-52 years). Overall, 128 women (52.7%) underwent bilateral prophylactic mastectomies, and 115 (47.3%) underwent contralateral prophylactic mastectomy. In the 371 mastectomies performed, 16 (4.3%) occult malignancies were diagnosed. Most of the occult malignancies were ductal carcinoma in situ (13 mastectomies, 3.5%), whereas 3 mastectomies (0.8%) contained invasive breast cancer. If Breast Imaging Reporting and Data System (BIRADS) 1-2 or BIRADS 3 findings were reported on preoperative magnetic resonance imaging (MRI), the rate of occult malignancy decreased to 3.0 and 2.8%, respectively, per mastectomy. The patient-level factors associated with a likelihood of occult breast cancer greater than 10% included a history of prior breast cancer, age exceeding 60 years, and BIRADS 4 findings on preoperative imaging. CONCLUSIONS Occult invasive malignancy was detected in less than 1% of the risk-reducing mastectomies performed for women with BRCA1/2 or PALB2 pathogenic variants. Sentinel lymph node biopsy can be safely avoided when BIRADS 1-3 findings are reported on preoperative MRI.
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Affiliation(s)
- Stephanie M Wong
- Department of Surgery, McGill University Medical School, Montreal, QC, Canada. .,Jewish General Hospital Stroll Cancer Prevention Centre, Montreal, QC, Canada. .,Department of Oncology, McGill University Medical School, Montreal, QC, Canada.
| | - Amina Ferroum
- Department of Surgery, McGill University Medical School, Montreal, QC, Canada.,Jewish General Hospital Stroll Cancer Prevention Centre, Montreal, QC, Canada
| | - Carla Apostolova
- Department of Surgery, McGill University Medical School, Montreal, QC, Canada.,Jewish General Hospital Stroll Cancer Prevention Centre, Montreal, QC, Canada
| | - Basmah Alhassan
- Department of Surgery, McGill University Medical School, Montreal, QC, Canada.,Jewish General Hospital Stroll Cancer Prevention Centre, Montreal, QC, Canada
| | - Ipshita Prakash
- Department of Surgery, McGill University Medical School, Montreal, QC, Canada.,Jewish General Hospital Stroll Cancer Prevention Centre, Montreal, QC, Canada.,Department of Pathology, McGill University, Montreal, QC, Canada
| | - Mark Basik
- Department of Surgery, McGill University Medical School, Montreal, QC, Canada.,Department of Oncology, McGill University Medical School, Montreal, QC, Canada
| | | | - Sarkis Meterissian
- Department of Surgery, McGill University Medical School, Montreal, QC, Canada.,Department of Oncology, McGill University Medical School, Montreal, QC, Canada
| | - Olga Aleynikova
- Department of Pathology, McGill University, Montreal, QC, Canada
| | - Nora Wong
- Jewish General Hospital Stroll Cancer Prevention Centre, Montreal, QC, Canada.,Department of Human Genetics, McGill University, Montreal, QC, Canada
| | - William D Foulkes
- Jewish General Hospital Stroll Cancer Prevention Centre, Montreal, QC, Canada.,Department of Human Genetics, McGill University, Montreal, QC, Canada
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Zarbo C, Brugnera A, Frigerio L, Celi C, Compare A, Dessì V, Giordano R, Malandrino C, Sina FP, Strepparava MG, Tessitore IV, Ventura M, Fruscio R. Cancer Anxiety Mediates the Association Between Satisfaction With Medical Communication and Psychological Quality of Life After Prophylactic Bilateral Salpingo-Oophorectomy. Front Psychol 2022; 13:840931. [PMID: 35356354 PMCID: PMC8959915 DOI: 10.3389/fpsyg.2022.840931] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 02/21/2022] [Indexed: 11/30/2022] Open
Abstract
Background Prophylactic Bilateral Salpingo-Oophorectomy (PBSO) reduces the risk of developing ovarian cancer. However, the psychological mechanisms that may affect post-surgery Quality of Life (QoL) among patients who underwent PBSO are still largely unknown. Thus, this study aimed at exploring the direct and indirect associations of satisfaction with medical communication and cancer anxiety on post-surgery QoL among women at high risk of developing ovarian cancer. Method Fifty-nine women (mean age: 50.64 ± 6.7 years) who underwent PBSO took part in this cross-sectional study, filling out a sociodemographic and clinical questionnaire, a battery of validated psychological measures and an ad hoc developed scale for the assessment of cancer anxiety. We first examined the correlations among all variables of interest, and then tested if cancer anxiety mediated the association between satisfaction with medical communication and post-surgery psychological QoL, controlling both for time from surgery and education. Results Post-surgery psychological QoL was unrelated from any sociodemographic or clinical variable. Cancer anxiety had a significant direct negative effect on psychological QoL, while satisfaction with medical communication had a significant positive direct effect on it. Finally, cancer anxiety significantly mediated the association between satisfaction with medical communication and post-surgery psychological QoL. Discussion Results suggest that post-surgery psychological QoL of patients who underwent PBSO may be increased with interventions, delivered in a genetic counselling setting, targeting quality of medical communication and cancer anxiety.
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Affiliation(s)
- Cristina Zarbo
- Unit of Epidemiological and Evaluation Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Agostino Brugnera
- Department of Human and Social Sciences, University of Bergamo, Bergamo, Italy
| | - Luigi Frigerio
- Department of Obstetrics & Gynaecology, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Chiara Celi
- Clinical Psychology Unit, ASST-Monza, Monza, Italy
| | - Angelo Compare
- Department of Human and Social Sciences, University of Bergamo, Bergamo, Italy
| | - Valentina Dessì
- Department of Human and Social Sciences, University of Bergamo, Bergamo, Italy
| | - Rosalba Giordano
- Department of Obstetrics & Gynaecology, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | - Chiara Malandrino
- Department of Obstetrics & Gynaecology, Hospital Papa Giovanni XXIII, Bergamo, Italy
| | | | - Maria Grazia Strepparava
- Clinical Psychology Unit, ASST-Monza, Monza, Italy.,Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
| | | | | | - Robert Fruscio
- Gynaecologic Surgery Unit, ASST-Monza, Monza, Italy.,Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
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Bilateral Prophylactic Nipple-Sparing Mastectomy: Analysis of the Risk-Reducing Effect in BRCA1/2 Mutation Carriers. Aesthetic Plast Surg 2022; 46:706-711. [PMID: 34342702 DOI: 10.1007/s00266-021-02506-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 07/24/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND Mutations in the BRCA1 or BRCA2 genes increase the lifetime risk of developing breast cancer to 68-72% by the age of 80. One of the modalities to manage the risk is a prophylactic mastectomy. Bilateral nipple-sparing mastectomy specifically offers the most favorable esthetic outcomes but the evidence for its oncological safety remains limited. Thus, we aimed to compare the occurrence of breast cancer between nipple-sparing mastectomy and surveillance groups of BRCA1 or BRCA 2 mutations carriers. MATERIALS AND METHODS BRCA1 or BRCA2-positive patients undergoing bilateral prophylactic nipple-sparing mastectomy at our department were identified. Only those unaffected by breast cancer were eligible. Each patient was pair-matched with a BRCA1 or BRCA2-positive patient of equal age from the surveillance group. Breast cancer incidence in both groups was recorded and the results were compared. RESULTS None of 105 patients who underwent NSM between 2009 and 2019 at a single institution with a mean follow-up time of 50 months developed breast cancer over this time period. One patient in this group died of an unrelated cause. Nine patients from 105 in the match-paired surveillance group were diagnosed with breast cancer during a mean follow-up time of 58.3 months, however, none of them died. CONCLUSION To the best of our knowledge, this is the largest single-center study of risk-reducing bilateral NSM in healthy BRCA1 or BRCA2 mutation carriers. Based on our results and those of other series, we conclude that NSM in its current form appears to be at least equally as safe as other types of mastectomy for preventing breast cancer in BRCA1 or BRCA2 mutation carriers. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Fu X, Tan W, Song Q, Pei H, Li J. BRCA1 and Breast Cancer: Molecular Mechanisms and Therapeutic Strategies. Front Cell Dev Biol 2022; 10:813457. [PMID: 35300412 PMCID: PMC8921524 DOI: 10.3389/fcell.2022.813457] [Citation(s) in RCA: 50] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 01/18/2022] [Indexed: 11/13/2022] Open
Abstract
Breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene, which is mainly involved in the repair of DNA damage, cell cycle regulation, maintenance of genome stability, and other important physiological processes. Mutations or defects in the BRCA1 gene significantly increase the risk of breast, ovarian, prostate, and other cancers in carriers. In this review, we summarized the molecular functions and regulation of BRCA1 and discussed recent insights into the detection and treatment of BRCA1 mutated breast cancer.
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Affiliation(s)
- Xiaoyu Fu
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Wei Tan
- Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, United States
| | - Qibin Song
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
| | - Huadong Pei
- Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States
| | - Juanjuan Li
- Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China
- Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China
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36
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Management of Hereditary Breast Cancer: An Overview. Breast Cancer 2022. [DOI: 10.1007/978-981-16-4546-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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37
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Pitiyarachchi O, Phillips KA, Friedlander M. Pregnancy induced hyperplasia of residual breast tissue following risk reducing contralateral mastectomy - simply interesting or a clinically important observation. Cancer Treat Res Commun 2022; 30:100504. [PMID: 34990902 DOI: 10.1016/j.ctarc.2021.100504] [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: 11/05/2021] [Revised: 12/27/2021] [Accepted: 12/28/2021] [Indexed: 10/19/2022]
Abstract
After a diagnosis of breast cancer women with increased genetic risk often have a risk reducing contralateral mastectomy, and may opt for a nipple or skin sparing mastectomy with immediate reconstruction. A variable amount of residual breast tissue remains which may substantially increase in volume during pregnancy. Whether this increases later risk of breast cancer is unknown. We describe the clinical details of 3 patients with a history of unilateral breast cancer, including 2 with a BRCA mutation, who developed hyperplasia of residual breast tissue in the 3rd trimester of a later pregnancy. They all had a delayed contralateral risk reducing skin sparing mastectomy and immediate reconstruction. Pregnancy occurred some years later. We summarise their management, review the literature and raise questions for discussion. All developed prominent hyperplasia of breast tissue in the 3rd trimester that was clinically obvious asymmetrical breast swelling in the reconstructed contralateral breast. MRI demonstrated substantial breast tissue. The risk of breast cancer, particularly in those at high genetic risk developing in the residual breast tissue is unknown but in view of the volume, breast tissue was excised postpartum. This phenomenon of pregnancy induced hyperplasia of breast tissue after risk reducing mastectomy is not well described .There is residual breast tissue following a risk reducing subcutaneous mastectomy. The risk factors include age and skin flap thickness. MRI can demonstrate the residual breast tissue. Pregnancy induced hyperplasia of residual breast tissue may occur after risk reducing mastectomy with a hypothetical increased risk of subsequent breast cancer.
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Affiliation(s)
- Omali Pitiyarachchi
- Department of Medical Oncology, Prince of Wales Hospital, Barker St, Randwick NSW 2031, Australia; Prince of Wales Clinical School, UNSW Medicine, Sydney, New South Wales, Australia
| | - Kelly-Anne Phillips
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; The Sir Peter MacCallum Department of Oncology, the University of Melbourne, Melbourne, Victoria, Australia
| | - Michael Friedlander
- Department of Medical Oncology, Prince of Wales Hospital, Barker St, Randwick NSW 2031, Australia; Prince of Wales Clinical School, UNSW Medicine, Sydney, New South Wales, Australia.
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Laustsen-Kiel CM, Lauritzen E, Langhans L, Engberg Damsgaard T. Study protocol for a 10-year prospective observational study, examining lymphoedema and patient-reported outcome after breast reconstruction. BMJ Open 2021; 11:e052676. [PMID: 34873005 PMCID: PMC8650483 DOI: 10.1136/bmjopen-2021-052676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Over the last decades, treatment of breast cancer has become increasingly more effective. Consequently, an increasing number of women are living with late effects of breast cancer treatment, including disfiguring scars, deformity or asymmetry of the breast, secondary lymphoedema and other physical and psychosocial late effects. Data from this study will provide knowledge on how to guide breast reconstruction in the future towards outcomes with fewer complications, higher long-term quality of life (QoL) and satisfaction with the aesthetic outcome. The development of secondary lymphoedema, for which the effect of breast reconstruction has yet to be established, will be thoroughly examined. METHODS AND ANALYSIS Women receiving breast reconstruction (autologous and implant based) at the Department of Plastic Surgery and Burns Treatment, Rigshospitalet, will be invited to participate. The patients will be followed for 10 years postoperatively. Demographic, health-related, oncological characteristics and treatment data will be registered. Validated assessment tools, such as the BREAST-Q and Beck Depression Inventory, will be used to measure an extensive range of clinical outcomes, including QoL, life and aesthetic satisfaction and depression. Arm range of motion will be measured with a goniometer and lymphoedema by bioimpedance spectroscopy, compared with circular arm measurements. ETHICS AND DISSEMINATION This study will be conducted according to the 5th version of the Helsinki Declaration. The regional ethical committee for Capital Region Denmark did not find the study notifiable, according to the law of the committee § 1, part 4. All data will be anonymised before its publication. This study will be conducted according to the Danish data protection regulation and is catalogued and approved by the Capital Region Head of Knowledge Centre. According to the Danish health law § 46, part 2, this study does not need the Danish Patient Safety Authority's approval. The findings of this study will be submitted to international peer-reviewed journals.
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Affiliation(s)
| | - Elisabeth Lauritzen
- Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark
| | - Linnea Langhans
- Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark
| | - Tine Engberg Damsgaard
- Department of Plastic Surgery and Burns Treatment, Rigshospitalet, Copenhagen, Denmark
- Institute of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark
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Association of Breast Surgeons of India (ABSI) Practical Consensus Statement, Recommendations, and Guidelines for the Treatment of Breast Cancer in India 2021—Indian Solutions for Indian Problems. Indian J Surg 2021. [DOI: 10.1007/s12262-021-03160-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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40
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Dick J, Aue V, Wesselmann S, Brédart A, Dolbeault S, Devilee P, Stoppa-Lyonnet D, Schmutzler RK, Rhiem K. Survey on Physicians' Knowledge and Training Needs in Genetic Counseling in Germany. Breast Care (Basel) 2021; 16:389-395. [PMID: 34602945 DOI: 10.1159/000511136] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 08/25/2020] [Indexed: 01/25/2023] Open
Abstract
Background In recent years, germline testing of women with a risk of developing breast and ovarian cancer has increased rapidly. This is due to lower costs for new high-throughput sequencing technologies and the manifold preventive and therapeutic options for germline mutation carriers. The growing demand for genetic counseling meets a shortfall of counselors and illustrates the need to involve the treating clinicians in the genetic testing process. This survey was undertaken to assess their state of knowledge and training needs in the field of genetic counseling and testing. Methods A cross-sectional survey within the European Bridges Study (Breast Cancer Risk after Diagnostic Gene Sequencing) was conducted among physician members (n = 111) of the German Cancer Society who were primarily gynecologists. It was designed to examine their experience in genetic counseling and testing. Results Overall, the study revealed a need for training in risk communication and clinical recommendations for persons at risk. One-third of respondents communicated only relative disease risks (31.5%) instead of absolute disease risks in manageable time spans. Moreover, almost one-third of the respondents (31.2%) communicated bilateral and contralateral risk-reducing mastectomy as an option for healthy women and unilateral-diseased breast cancer patients without mutations in high-risk genes (e.g. BRCA1 or BRCA2). Most respondents expressed training needs in the field of risk assessment models, the clinical interpretation of genetic test results, and the decision-making process. Conclusion The survey demonstrates a gap of genetic and risk literacy in a relevant proportion of physicians and the need for appropriate training concepts.
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Affiliation(s)
- Julia Dick
- Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany
| | - Viktoria Aue
- Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany
| | | | - Anne Brédart
- Supportive Care Department, Psycho-Oncology Unit, Institut Curie, Paris, France.,University Paris Descartes, Boulogne-Billancourt, France
| | - Sylvie Dolbeault
- Supportive Care Department, Psycho-Oncology Unit, Institut Curie, Paris, France.,Centre de Recherche en Épidémiologie et Santé des Populations (CESP), University Paris-Sud, UVSQ, INSERM, University Paris-Saclay, Villejuif Cedex, France
| | - Peter Devilee
- Departments of Human Genetics and Pathology, Leiden University Medical Centre, Leiden, The Netherlands
| | | | - Rita K Schmutzler
- Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany
| | - Kerstin Rhiem
- Center for Hereditary Breast and Ovarian Cancer and Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany
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41
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Utility and Outcomes of Pre-Operative Screening Breast MRI for Planned Bilateral Prophylactic Mastectomy in High-Risk Patients. AJR Am J Roentgenol 2021; 218:241-248. [PMID: 34523953 DOI: 10.2214/ajr.21.26561] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Background: There is a paucity of data and consensus guidelines on the utility of preoperative MRI for planned bilateral prophylactic mastectomy. Objective: To evaluate the utility of breast MRI performed in high-risk patients for the indication of planned bilateral prophylactic mastectomy, with attention to diagnostic performance for breast cancer detection. A secondary aim was to assess the potential impact of breast MRI findings on the decision to perform sentinel lymph node biopsy at the time of prophylactic mastectomy. Methods: A retrospective database review identified MRI examinations performed at an academic medical center from August 2003 to January 2020 for the indication of planned bilateral prophylactic mastectomy. Patient demographics, imaging findings, operative details, and pathology were recorded. BI-RADS 1 and 2 assessments were considered negative examinations, and BI-RADS 3, 4, and 5 were considered positive examinations. Descriptive statistics and performance metrics were calculated. Results: The final cohort included 53 patients (mean age, 45 years). Most (35/53; 66%) studies were baseline examinations. Of the 53 patients, 31 (58%) had a negative MRI, and 22 (42%) a positive MRI. MRI detected two malignancies, both assessed as BI-RADS 4 (one invasive lobular carcinoma and one high-grade DCIS). The patient with invasive lobular cancer underwent sentinel lymph node biopsy at the time of mastectomy, which demonstrated metastasis. Breast MRI had sensitivity of 100.0% and specificity of 60.8% for overall breast cancer detection, and sensitivity of 100.0% and specificity of 59.6% for invasive cancer detection. Conclusion: Preoperative MRI for planned bilateral prophylactic mastectomy detected all cancers, indicating a potential role for MRI in impacting surgical decision making. Clinical Impact: Given the high NPV for cancer, our results suggest that lymph node biopsy may be safely avoided in patients with a negative MRI. This is clinically relevant since sentinel nodes cannot be identified post-mastectomy.
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42
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Berger ER, Golshan M. Surgical Management of Hereditary Breast Cancer. Genes (Basel) 2021; 12:1371. [PMID: 34573353 PMCID: PMC8470490 DOI: 10.3390/genes12091371] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 08/26/2021] [Accepted: 08/26/2021] [Indexed: 12/26/2022] Open
Abstract
The identification that breast cancer is hereditary was first described in the nineteenth century. With the identification of the BRCA1 and BRCA 2 breast/ovarian cancer susceptibility genes in the mid-1990s and the introduction of genetic testing, significant advancements have been made in tailoring surveillance, guiding decisions on medical or surgical risk reduction and cancer treatments for genetic variant carriers. This review discusses various medical and surgical management options for hereditary breast cancers.
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Affiliation(s)
- Elizabeth R. Berger
- Department of Surgery, School of Medicine, Yale University, New Haven, CT 06511, USA;
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43
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Alaofi RK, Nassif MO, Al-Hajeili MR. Prophylactic mastectomy for the prevention of breast cancer: Review of the literature. Avicenna J Med 2021; 8:67-77. [PMID: 30090744 PMCID: PMC6057165 DOI: 10.4103/ajm.ajm_21_18] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The high incidence and recurrence rate of breast cancer has influenced multiple strategies such as early detection with imaging, chemoprevention and surgical interventions that serve as preventive measures for women at high risk. Prophylactic mastectomy is one of the growing strategies of breast cancer risk reduction that is of a special importance for breast cancer gene mutation carriers. Women with personal history of cancerous breast lesions may consider ipsilateral or contralateral mastectomy as well. Existing data showed that mastectomy effectively reduces breast cancer risk. However, careful risk estimation is necessary to wisely select individuals who will benefit from preventing breast cancer.
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Affiliation(s)
- Rawan K Alaofi
- Taibah University College of Medicine, Medina, Saudi Arabia
| | - Mohammed O Nassif
- Department of Surgery, King Abdulaziz University, Jeddah, Saudi Arabia
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44
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Houvenaeghel G, Cohen M, Dammacco MA, D'Halluin F, Regis C, Gutowski M, Acker O, Fournier M, Bannier M, Lusque A, Jouve E. Prophylactic nipple-sparing mastectomy with immediate breast reconstruction: results of a French prospective trial. Br J Surg 2021; 108:296-301. [PMID: 33793719 DOI: 10.1093/bjs/znaa082] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 10/14/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR) is used increasingly when performing a prophylactic mastectomy. Few prospective studies have reported on complication rates. This complementary trial to the French prospective multicentre MAPAM trial aimed to evaluate the nipple-areola complex (NAC) necrosis rate in prophylactic NSM with IBR. METHODS Patient characteristics and surgical data were recorded. Morbidity after prophylactic NSM with a focus on NAC necrosis was analysed. RESULTS Among 59 women undergoing prophylactic NSM, 19 (32 per cent) of the incisions were partly on the NAC. Reconstructions were performed with 46 definitive implants and 13 expanders. The crude rate of postoperative complications was 25 per cent (15 patients). Complete NAC necrosis was reported in two women (3 per cent) and partial or total necrosis in nine (15 per cent). No NAC resection was necessary. Median BMI was lower in women with total or partial NAC necrosis compared with the others (20.0 versus 21.3 kg/m2 respectively; P = 0.034). CONCLUSION Results of this prospective study confirm that prophylactic NSM with IBR is associated with a low risk of total NAC necrosis.
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Affiliation(s)
- G Houvenaeghel
- Department of Surgical Oncology, Paoli Calmettes Institute and Centre de Recherche en Cancerérologie de Marseille (CRCM), Aix-Marseille University, Marseille, France
| | - M Cohen
- Department of Surgical Oncology, Paoli Calmettes Institute, Marseille, France
| | - M A Dammacco
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - F D'Halluin
- Surgery Department, L'Etablissement Rennais du Sein, Centre Hospitalier Privé St Grégoire, St Grégoire, France
| | - C Regis
- Department of Surgical Oncology, Centre Oscar Lambret, Lille, France
| | - M Gutowski
- Department of Surgical Oncology, Institut du Cancer de Montpellier Val d'Aurelle, Montpellier, France
| | - O Acker
- Surgery Department, Pôle Santé Léonard de Vinci, Chambray les Tours, France
| | - M Fournier
- Department of Surgical Oncology, Institut Bergonie, Bordeaux, France
| | - M Bannier
- Department of Surgical Oncology, Paoli Calmettes Institute, Marseille, France
| | - A Lusque
- Department of Biostatistics, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France
| | - E Jouve
- Department of Surgical Oncology, Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France
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Safra T, Waissengrin B, Gerber D, Bernstein-Molho R, Klorin G, Salman L, Josephy D, Chen-Shtoyerman R, Bruchim I, Frey MK, Pothuri B, Muggia F. Breast cancer incidence in BRCA mutation carriers with ovarian cancer: A longitudal observational study. Gynecol Oncol 2021; 162:715-719. [PMID: 34172288 DOI: 10.1016/j.ygyno.2021.06.009] [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: 03/22/2021] [Accepted: 06/10/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVES We evaluated the incidence of breast cancer and overall survival in a multi-center cohort of ovarian cancer patients carrying BRCA1/2 mutations in order to assess risks and formulate optimal preventive interventions and/or surveillance. METHODS Medical records of 502 BRCA1/2 mutation carriers diagnosed with ovarian cancer between 2000 and 2018 at 7 medical centers in Israel and one in New York were retrospectively analyzed for breast cancer diagnosis. Data included demographics, type of BRCA mutations, surveillance methods, timing of breast cancer diagnosis, and family history of cancer. RESULTS The median age at diagnosis of ovarian cancer was 55.8 years (range, 23.9-90.1). A third (31.5%) had a family history of breast cancer and 17.1% of ovarian cancer. Most patients (67.3%) were Ashkenazi Jews, 72.9% were BRCA1 carriers. Breast cancer preceded ovarian cancer in 17.5% and was diagnosed after ovarian cancer in 6.2%; an additional 2.2% had a synchronous presentation. Median time to breast cancer diagnosis after ovarian cancer was 46.0 months (range, 11-168). Of those diagnosed with both breast cancer and ovarian cancer (n = 31), 83.9% and 16.1% harbored BRCA1 and BRCA2 mutations, respectively. No deaths from breast cancer were recorded. Overall survival did not differ statistically between patients with an ovarian cancer diagnosis only and those diagnosed with breast cancer after ovarian cancer. CONCLUSION The low incidence of breast cancer after ovarian cancer in women carrying BRCA1/2 mutations suggests that routine breast surveillance, rather than risk-reducing surgical interventions, may be sufficient in ovarian cancer survivors.
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Affiliation(s)
- Tamar Safra
- New York University Cancer Institute, New York, ,NY, United States of America; Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel.
| | | | - Deanna Gerber
- New York University Cancer Institute, New York, ,NY, United States of America
| | - Rinat Bernstein-Molho
- Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel; Chaim Sheba Medical Center, Breast Cancer Center, Oncology Institute, Ramat Gan, Israel
| | - Geula Klorin
- Rambam Health Care Campus, Haifa, Israel; Technion Institute of Technology, Rappaport School of Medicine, Haifa, Israel
| | | | - Dana Josephy
- Tel Aviv University Sackler School of Medicine, Tel Aviv, Israel; Meir Medical Center, Kfar Saba, Israel
| | - Rakefet Chen-Shtoyerman
- The Oncogenetic Clinic, The Clinical Genetics Institute, Kaplan Medical Center, Rehovot, Israel; Ariel University, Ariel, Israel
| | - Ilan Bruchim
- Technion Institute of Technology, Rappaport School of Medicine, Haifa, Israel; Hillel Yaffe Medical Center, Hadera, Israel
| | - Melissa K Frey
- New York University Cancer Institute, New York, ,NY, United States of America
| | - Bhavana Pothuri
- New York University Cancer Institute, New York, ,NY, United States of America
| | - Franco Muggia
- New York University Cancer Institute, New York, ,NY, United States of America
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Lapointe J, Dorval M, Chiquette J, Joly Y, Guertin JR, Laberge M, Gekas J, Hébert J, Pomey MP, Cruz-Marino T, Touhami O, Blanchet Saint-Pierre A, Gagnon S, Bouchard K, Rhéaume J, Boisvert K, Brousseau C, Castonguay L, Fortier S, Gosselin I, Lachapelle P, Lavoie S, Poirier B, Renaud MC, Ruizmangas MG, Sebastianelli A, Roy S, Côté M, Racine MM, Roy MC, Côté N, Brisson C, Charette N, Faucher V, Leblanc J, Dubeau MÈ, Plante M, Desbiens C, Beaumont M, Simard J, Nabi H. A Collaborative Model to Implement Flexible, Accessible and Efficient Oncogenetic Services for Hereditary Breast and Ovarian Cancer: The C-MOnGene Study. Cancers (Basel) 2021; 13:cancers13112729. [PMID: 34072979 PMCID: PMC8198545 DOI: 10.3390/cancers13112729] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/12/2021] [Accepted: 05/25/2021] [Indexed: 01/04/2023] Open
Abstract
Simple Summary We recently developed an oncogenetic model to overcome the unprecedented demand for genetic counseling and testing for hereditary breast and ovarian cancer. Quality and performance indicators showed that the implementation of this model improved access to genetic counseling and minimized delays for genetic tests for patients, who reported to be overwhelmingly satisfied with the process. However, it remains unknown whether this model is robust and sustainable or requires adjustments. In addition, whether the model could be deployed elsewhere remains also to be elucidated. The C-MOnGene study was therefore designed to gain an in-depth understanding of the context in which the model was developed and implemented, and document the lessons that can be learned to optimize oncogenetic services delivery in other settings. Abstract Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants’ understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.
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Affiliation(s)
- Julie Lapointe
- Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, 1050, Chemin Ste-Foy, Local J0-01, Québec, QC G1S 4L8, Canada; (J.L.); (M.D.); (J.C.); (J.R.G.); (M.L.); (K.B.); (J.S.)
| | - Michel Dorval
- Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, 1050, Chemin Ste-Foy, Local J0-01, Québec, QC G1S 4L8, Canada; (J.L.); (M.D.); (J.C.); (J.R.G.); (M.L.); (K.B.); (J.S.)
- Centre de Recherche CISSS Chaudière-Appalaches, 143 Rue Wolfe, Lévis, QC G6V 3Z1, Canada;
- Faculté de Pharmacie, Université Laval, 1050 Av de la Médecine, Québec, QC G1V 0A6, Canada
| | - Jocelyne Chiquette
- Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, 1050, Chemin Ste-Foy, Local J0-01, Québec, QC G1S 4L8, Canada; (J.L.); (M.D.); (J.C.); (J.R.G.); (M.L.); (K.B.); (J.S.)
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Yann Joly
- Institut de Recherche du Centre Universitaire de Santé McGill, 2155 Rue Guy, 5e étage, Montréal, QC H3H 2R9, Canada;
- Département de Génétique Humaine et Unité de Bioéthique, Faculté de Médecine, Université McGill, 3605 Rue de la Montagne Montréal, Montréal, QC H3G 2M1, Canada
| | - Jason Robert Guertin
- Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, 1050, Chemin Ste-Foy, Local J0-01, Québec, QC G1S 4L8, Canada; (J.L.); (M.D.); (J.C.); (J.R.G.); (M.L.); (K.B.); (J.S.)
- Département de Médecine Sociale et Préventive, Faculté de Médecine, Université Laval, 1050 Avenue de la Médecine, Université Laval, Québec, QC G1V 0A6, Canada
| | - Maude Laberge
- Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, 1050, Chemin Ste-Foy, Local J0-01, Québec, QC G1S 4L8, Canada; (J.L.); (M.D.); (J.C.); (J.R.G.); (M.L.); (K.B.); (J.S.)
- Vitam, Centre de Recherche en Santé Durable, Université Laval, 2525, Chemin de la Canardière, Québec, QC G1J 0A4, Canada
- Département des Opérations et Systèmes de Décision, Faculté des Sciences de l’Administration, Université Laval, 2325 Rue de la Terrasse Université Laval, Québec, QC G1V 0A6, Canada
| | - Jean Gekas
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Johanne Hébert
- Centre de Recherche CISSS Chaudière-Appalaches, 143 Rue Wolfe, Lévis, QC G6V 3Z1, Canada;
- Département des Sciences Infirmières, Université du Québec à Rimouski (UQAR), Campus de Lévis, 1595 Boulevard Alphonse-Desjardins, Lévis, QC G6V 0A6, Canada
| | - Marie-Pascale Pomey
- Centre de Recherche du CHUM, 900, Rue Saint-Denis, Montréal, QC H2X 0A9, Canada;
- Département de Gestion, Évaluation et Politique de Santé, Faculté de Médecine, Université de Montréal, 7101 Avenue du Parc, 3e Étage, Montréal, QC H3N 1X9, Canada
| | - Tania Cruz-Marino
- CIUSSS Saguenay Lac-St-Jean, 930 Rue Jacques-Cartier Est, Chicoutimi, QC G7H 7K9, Canada; (T.C.-M.); (O.T.); (S.G.); (V.F.); (J.L.); (M.-È.D.)
| | - Omar Touhami
- CIUSSS Saguenay Lac-St-Jean, 930 Rue Jacques-Cartier Est, Chicoutimi, QC G7H 7K9, Canada; (T.C.-M.); (O.T.); (S.G.); (V.F.); (J.L.); (M.-È.D.)
| | - Arnaud Blanchet Saint-Pierre
- CISSS Bas St-Laurent, 150 Av Rouleau, Rimouski, QC G5L 5T1, Canada; (A.B.S.-P.); (M.-C.R.); (N.C.); (C.B.); (N.C.)
| | - Sylvain Gagnon
- CIUSSS Saguenay Lac-St-Jean, 930 Rue Jacques-Cartier Est, Chicoutimi, QC G7H 7K9, Canada; (T.C.-M.); (O.T.); (S.G.); (V.F.); (J.L.); (M.-È.D.)
| | - Karine Bouchard
- Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, 1050, Chemin Ste-Foy, Local J0-01, Québec, QC G1S 4L8, Canada; (J.L.); (M.D.); (J.C.); (J.R.G.); (M.L.); (K.B.); (J.S.)
| | - Josée Rhéaume
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Karine Boisvert
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Claire Brousseau
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Lysanne Castonguay
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Sylvain Fortier
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Isabelle Gosselin
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Philippe Lachapelle
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Sabrina Lavoie
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Brigitte Poirier
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Marie-Claude Renaud
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Maria-Gabriela Ruizmangas
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Alexandra Sebastianelli
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Stéphane Roy
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Madeleine Côté
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | | | - Marie-Claude Roy
- CISSS Bas St-Laurent, 150 Av Rouleau, Rimouski, QC G5L 5T1, Canada; (A.B.S.-P.); (M.-C.R.); (N.C.); (C.B.); (N.C.)
| | - Nathalie Côté
- CISSS Bas St-Laurent, 150 Av Rouleau, Rimouski, QC G5L 5T1, Canada; (A.B.S.-P.); (M.-C.R.); (N.C.); (C.B.); (N.C.)
| | - Carmen Brisson
- CISSS Bas St-Laurent, 150 Av Rouleau, Rimouski, QC G5L 5T1, Canada; (A.B.S.-P.); (M.-C.R.); (N.C.); (C.B.); (N.C.)
| | - Nelson Charette
- CISSS Bas St-Laurent, 150 Av Rouleau, Rimouski, QC G5L 5T1, Canada; (A.B.S.-P.); (M.-C.R.); (N.C.); (C.B.); (N.C.)
| | - Valérie Faucher
- CIUSSS Saguenay Lac-St-Jean, 930 Rue Jacques-Cartier Est, Chicoutimi, QC G7H 7K9, Canada; (T.C.-M.); (O.T.); (S.G.); (V.F.); (J.L.); (M.-È.D.)
| | - Josianne Leblanc
- CIUSSS Saguenay Lac-St-Jean, 930 Rue Jacques-Cartier Est, Chicoutimi, QC G7H 7K9, Canada; (T.C.-M.); (O.T.); (S.G.); (V.F.); (J.L.); (M.-È.D.)
| | - Marie-Ève Dubeau
- CIUSSS Saguenay Lac-St-Jean, 930 Rue Jacques-Cartier Est, Chicoutimi, QC G7H 7K9, Canada; (T.C.-M.); (O.T.); (S.G.); (V.F.); (J.L.); (M.-È.D.)
| | - Marie Plante
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Christine Desbiens
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Martin Beaumont
- CHU de Québec-Université Laval, 1050, Chemin Ste-Foy, Québec, QC G1S 4L8, Canada; (J.G.); (J.R.); (K.B.); (C.B.); (L.C.); (S.F.); (I.G.); (P.L.); (S.L.); (B.P.); (M.-C.R.); (M.-G.R.); (A.S.); (S.R.); (M.C.); (M.P.); (C.D.); (M.B.)
| | - Jacques Simard
- Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, 1050, Chemin Ste-Foy, Local J0-01, Québec, QC G1S 4L8, Canada; (J.L.); (M.D.); (J.C.); (J.R.G.); (M.L.); (K.B.); (J.S.)
- Département de Médecine moléculaire, Faculté de Médecine, Université Laval, 1050 Avenue de la Médecine, Québec, QC G1V 0A6, Canada
| | - Hermann Nabi
- Centre de Recherche du CHU de Québec-Université Laval, Hôpital du Saint-Sacrement, 1050, Chemin Ste-Foy, Local J0-01, Québec, QC G1S 4L8, Canada; (J.L.); (M.D.); (J.C.); (J.R.G.); (M.L.); (K.B.); (J.S.)
- Département de Médecine Sociale et Préventive, Faculté de Médecine, Université Laval, 1050 Avenue de la Médecine, Université Laval, Québec, QC G1V 0A6, Canada
- Correspondence: ; Tel.: +1-418-525-4444 (ext. 82800)
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Risk-Reducing Mastectomy and Reconstruction Following Prophylactic Breast Irradiation: Hope Sustained. Cancers (Basel) 2021; 13:cancers13112694. [PMID: 34070748 PMCID: PMC8198915 DOI: 10.3390/cancers13112694] [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: 03/22/2021] [Revised: 05/10/2021] [Accepted: 05/26/2021] [Indexed: 11/16/2022] Open
Abstract
Simple Summary In this study we report the outcome of salvage mastectomy and reconstruction in 11 BRCA mutation carrier patients that participated in a clinical trial of prophylactic contralateral breast irradiation and suffered reoccurrences of breast cancer in either the ipsilateral or contralateral breast or elected to have the procedure for risk reduction. Patients’ satisfaction and physicians’ assessment of the cosmetic outcome were not inferior for previously irradiated compared to non-irradiated breasts. These results are encouraging and support continuing research as well as a discussion of risk-reduction alternatives besides mastectomy, including prophylactic breast irradiation, in BRCA1/2 mutation carriers. Abstract Risk-reducing mastectomy (RRM) is often advocated for BRCA1/2 mutation carriers who face a heightened lifetime risk of breast cancer. However, many carrier patients seek alternative risk-reducing measures. In a phase II nonrandomized trial, we previously reported that prophylactic irradiation to the contralateral breast among BRCA carriers undergoing breast-conserving treatment significantly reduced subsequent contralateral breast cancer. Herein, we report the outcome of salvage mastectomy and reconstruction in 11 patients that suffered reoccurrences of breast cancer in either the ipsilateral or contralateral breast or elected to have the procedure for risk reduction during the eight-year follow-up period. Patients’ satisfaction with the procedure and physicians’ assessment of the cosmetic outcome were not inferior for previously irradiated compared to non-irradiated breasts. Although the numbers are small, the results are encouraging and sustain hope in a challenging population. Our findings support continuing research as well as a discussion of risk-reduction alternatives besides mastectomy, including prophylactic breast irradiation, in BRCA1/2 mutation carriers.
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The incisional hernia epidemic: evaluation of outcomes, recurrence, and expenses using the healthcare cost and utilization project (HCUP) datasets. Hernia 2021; 25:1667-1675. [PMID: 33835324 DOI: 10.1007/s10029-021-02405-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 03/29/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Incisional hernias (IH) following abdominal surgery persist as morbid, costly, and multi-disciplinary surgical challenges. Using longitudinal, multi-state, administrative claims data (HCUP State Inpatient Databases (SID)); (HCUP State Ambulatory Surgery and Services Databases (SASD)), we aimed to characterize the epidemiology, outcomes, recurrence, and costs of IH. STUDY DESIGN 529,108 patients undergoing abdominal surgery in 2010 across six specialties (colorectal, general/bariatric, hepatobiliary, obstetrics/gynecology, urology, and vascular) were identified within inpatient and ambulatory databases for Florida (FL), Iowa (IA), Nebraska (NE), New York (NY), and Utah (UT). IH repairs, complications, and expenditures were assessed through 2014. Predictive regression modeling was validated using a training set of 1000 bootstrapped repetitions. RESULTS 16,169 (3.1%) patients developed hernias requiring repair (4.3-year mean follow-up), 3176 (20%) underwent recurrent repair, and 731 (23%) underwent re-recurrent repair. Patients with IH had increased readmissions (6.6 vs. 2.4), morbidity (39 vs. 8% surgical and 22 vs. 7% medical), and costs ($46,000 vs. $25,000) when compared to patients without IH (p < 0.001). IH expenditures totaled $875 million: initial ($687 million), recurrent ($155 million), and re-recurrent hernias ($33 million). IH predominated in colorectal (10%), hepatobiliary (8%), and vascular (5%) procedures. Of 31 significant independent IH risk factors (p < 0.001), obesity, age, smoking, open surgery, and prior surgery were pervasive across surgical specialties. CONCLUSION IH represents an unremitting surgical epidemic associated with considerable morbidity, costs, and features consistent with a chronic disease state. We define critical pervasive risk factors (obesity, age, smoking open surgery, and prior surgery) independently associated with IH across surgical disciplines. With failed repairs, subsequent success becomes less likely, increasing morbidity and costs-underscoring the critical importance of optimal treatment and prevention.
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Canadian cost-effectiveness model of BRCA-driven surgical prevention of breast/ovarian cancers compared to treatment if cancer develops. Int J Technol Assess Health Care 2021; 36:104-112. [PMID: 32423520 DOI: 10.1017/s0266462319003519] [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] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To assess the cost effectiveness from a Canadian perspective of index patient germline BRCA testing and then, if positive, family members with subsequent risk-reducing surgery (RRS) in as yet unaffected mutation carriers compared with no testing and treatment of cancer when it develops. METHODS A patient level simulation was developed comparing outcomes between two groups using Canadian data. Group 1: no mutation testing with treatment if cancer developed. Group 2: cascade testing (index patient BRCA tested and first-/second-degree relatives tested if index patient/first-degree relative is positive) with RRS in carriers. End points were the incremental cost-effectiveness ratio (ICER) and budget impact. RESULTS There were 29,102 index patients: 2,786 ovarian cancer and 26,316 breast cancer (BC). Using the base-case assumption of 44 percent and 21 percent of women with a BRCA mutation receiving risk-reducing bilateral salpingo-oophorectomy and risk-reducing mastectomy, respectively, testing was cost effective versus no testing and treatment on cancer development, with an ICER of CAD 14,942 (USD 10,555) per quality-adjusted life-year (QALY), 127 and 104 fewer cases of ovarian and BC, respectively, and twenty-one fewer all-cause deaths. Testing remained cost effective versus no testing at the commonly accepted North American threshold of approximately CAD 100,000 (or USD 100,000) per QALY gained in all scenario analyses, and cost effectiveness improved as RRS uptake rates increased. CONCLUSIONS Prevention via testing and RRS is cost effective at current RRS uptake rates; however, optimization of uptake rates and RRS will increase cost effectiveness and can provide cost savings.
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Akhoon N. Precision Medicine: A New Paradigm in Therapeutics. Int J Prev Med 2021; 12:12. [PMID: 34084309 PMCID: PMC8106271 DOI: 10.4103/ijpvm.ijpvm_375_19] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 02/04/2020] [Indexed: 11/26/2022] Open
Abstract
A key goal of clinical care is to treat patients as individuals and to approach therapeutics in such a way that it has optimal efficacy and minimal toxicity. With swift technological advances, such as genomic sequencing and molecular targeted drug exploitation, the concept of precision medicine has been robustly promoted in recent years. Precision medicine endeavors to demarcate diseases using multiple data sources from genomics to digital health metrics in order to facilitate an individualized yet "evidence-based" decision regarding diagnostic and therapeutic approaches. In this way, therapeutics can be centered toward patients based on their molecular presentation rather than grouping them into broad categories with a "one size fits all" approach. This review article is aimed to provide a broad overview of the advent and emergence of precision medicine in view of its current implications.
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Affiliation(s)
- Neha Akhoon
- Department of Pharmacology, Armed Forces Medical College, Pune, Maharashtra, India
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