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乳腺癌易感基因BRCA1和BRCA2是重要的抑癌基因，如果发生致病突变，容易发生乳腺癌、卵巢癌等恶性肿瘤。不过，对于BRCA2突变乳腺癌患者，各种治疗方法对生存结局的影响尚不明确。 2021年2月18日，英国癌症研究基金会《英国癌症杂志》在线发表英国、澳大利亚、意大利、波兰、加拿大、美国、挪威、奥地利的研究报告，探讨了双侧卵巢切除术和其他治疗方法对种系BRCA2突变患者乳腺癌相关生存结局的影响。 该研究对5个地区（北美、波兰、澳大利亚、英国、意大利）前瞻或回顾研究数据进行分析，确定664例早期乳腺癌种系BRCA2突变女性。从诊断乳腺癌到乳腺癌所致死亡，对这些女性进行中位7.2年随访。根据患者报告和医疗记录，获得肿瘤特征和癌症治疗方法。通过多因素比例风险回归模型对其他治疗方法和预后特征进行校正后，确定生存结局预测因素。 结果，10年乳腺癌相关生存比例：
因此，该多中心大样本回顾研究结果表明，对于种系BRCA2突变的乳腺癌女性，雌激素受体阳性与阴性相比、化疗与未化疗相比，生存结局相似。双侧卵巢切除与未切除相比，乳腺癌所致死亡风险显著较低，制定治疗计划时应予考虑，故有必要进一步开展多中心大样本前瞻研究进行验证。 Br J Cancer. 2021 Feb 18. Online ahead of print. Survival from breast cancer in women with a BRCA2 mutation by treatment. D. Gareth Evans, Kelly-Anne Phillips, Roger L. Milne, Robert Fruscio, Cezary Cybulski, Jacek Gronwald, Jan Lubinski, Tomasz Huzarski, Zerin Hyder, Claire Forde, Kelly Metcalfe, Leigha Senter, Jeffrey Weitzel, Nadine Tung, Dana Zakalik, Maria Ekholm, Ping Sun, Steven A. Narod, Maria Blasińska-Morawiec, Maria Chosia, Kazimierz Drosik, Sylwia Gozdecka-Grodecka, Stanislaw Gozdz, Ewa Grzybowska, Arkadiusz Jeziorski, Aldona Karczewska, Radzislaw Kordek, Agnieszka Synowiec, Beata Kozak-Klonowska, Katarzyna Lamperska, Dariusz Lange, Andrzej Mackiewicz, Jerzy Wladyslaw Mitus, Stanislas Niepsuj, Oleg Oszurek, Karol Gugala, Zbigniew Morawiec, Tomasz Mierzwa, Michal Posmyk, Janusz Rys, Cezary Szczylik, Michal Uciński, Krzysztof Urbański, Bernard Wasko, Piotr Wandzel, Michael Friedlander, Sue Anne McLachlan, Stephanie Nesci, Sandra Picken, Sarah O'Connor, Lucy Stanhope, Andrea Eisen, Kevin Sweet, Raymond Kim, William Foulkes, Pal Moller, Susan Neuhausen, Carey Cullinane, Charis Eng, Peter Ainsworth, Fergus Couch, Christian Singer, Beth Karlan, Wendy McKinnon, Marie Wood; kConFab Investigators, Polish Hereditary Breast Cancer Consortium, Hereditary Breast Cancer Clinical Study Group. The University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, The Christie, Manchester, UK; University of Melbourne, Melbourne, Australia; Peter MacCallum Cancer Centre, Melbourne, Australia; Monash University, Clayton, Australia; Cancer Council Victoria, Melbourne, Australia; Prince of Wales Hospital, Randwick, Australia; St Vincent's Hospital, Fitzroy, Australia; University of Milan-Bicocca, Milan, Italy; Pomeranian Medical University, Szczecin, Poland; Copernicus Memorial Hospital, Lodz, Poland; Regional Cancer Center, Opole, Poland; Poznan University of Medical Sciences, Poznań, Poland; Holycross Cancer Centre, Kielce, Poland; Maria Sklodowska-Curie Institute, Gliwice, Poland; Medical University of Lodz, Lodz, Poland; University School of Medical Sciences at Great Poland Cancer Center, Poznań, Poland; Military Institute of Medicine, Warsaw, Poland; Greater Poland Cancer Centre, Poznan, Poland; Maria Sklodowska-Curie Institute-Oncology Center, Gliwice, Poland; Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Krakow, Poland; Maria Sklodowska-Curie Memorial Institute of Oncology, Krakow, Poland; Regional Oncology Hospital, Olsztyn, Poland; Regional Oncology Hospital, Bydgoszcz, Poland; Regional Oncology Center, Bialystok, Poland; Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Krakow, Poland; Military Hospital, Warsaw, Poland; Institute of Oncology, Krakow, Poland; Regional Hospital, Rzeszów, Poland; Regional Hospital Bielsko-Biala, Bielsko-Biala, Poland; Women's College Hospital, Toronto, ON, Canada; Sunnybrook Health Sciences Centre, Toronto, Canada; University Health Network, Toronto, Canada; McGill University, Montreal, Canada; London Health Sciences Centre, London, Canada; Ohio State University, Columbus, Ohio, USA; Ohio State University, Columbus, OH, USA; City of Hope, Duarte, CA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA; Beaumont Health, Royal Oak, MI, USA; Cleveland Clinic, Cleveland, Ohio, USA; Mayo Clinic, Rochester, MN, USA; University of California, Los Angeles, CA, USA; University of Vermont, Burlington, VT, USA; Norwegian Radium Hospital, Oslo, Norway; Medical University of Vienna, Vienna, Austria. BACKGROUND: The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation. METHODS: We identified 664 women with stage I-III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features. RESULTS: The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR=1.23 (95% CI, 0.62-2.45, p=0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR=0.45; 95% CI, 0.28-0.72, p=0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65-1.53: p=0.56). CONCLUSIONS: For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan. DOI: 10.1038/s41416-020-01164-1
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