降低风险手术与年轻乳腺癌BRCA携带者生存之间的关联：一项国际队列研究。
Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: an international cohort study.
作者信息
Blondeaux Eva, Sonnenblick Amir, Agostinetto Elisa, Bas Raphaëlle, Kim Hee J, Franzoi Maria A, Bernstein-Molho Rinat, Linn Sabine, Kwong Ava, Pogoda Katarzyna, Balmana Judith, Smeets Ann, Bajpai Jyoti, Moore Halle C F, Partridge Ann H, Phillips Kelly-Anne, Toss Angela, Rousset-Jablonski Christine, Peccatori Fedro A, Renaud Tiphaine, Ferrari Alberta, Paluch-Shimon Shani, Mando Pablo, Lee Jeong E, Fruscio Robert, Cui Wanda, Wong Stephanie M, Vernieri Claudio, Ruddy Kathryn J, Dieci Maria V, Matikas Alexios, Rozenblit Mariya, Guven Deniz C, Lee Minna, Villarreal-Garza Cynthia, Hwang Shelley E, De Marchis Laura, Puglisi Fabio, Kemp Zoe, Meireles Pedro A, Parokonnaya Anastasia, Werutsky Gustavo, Okano Maiko, Azim Hatem A, Mati Kleida, Rosenberg Shoshana, Gelber Richard, Boni Luca, Lambertini Matteo
机构信息
Clinical Trial Unit, Epidemiologia Clinica, Ospedale Policlinico San Martino, Genova, Italy.
The Oncology Division, Tel Aviv Sourasky Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
出版信息
Lancet Oncol. 2025 Jun;26(6):759-770. doi: 10.1016/S1470-2045(25)00152-4. Epub 2025 May 8.
BACKGROUND
Little evidence exists on the effect of risk-reducing surgeries in young BRCA carriers with a previous history of breast cancer. We investigated the association between risk-reducing mastectomy (RRM) or risk-reducing salpingo-oophorectomy (RRSO), or both procedures, with survival outcomes in a large global cohort of young BRCA carriers with previous breast cancer.
METHODS
The BRCA BCY Collaboration is an international, hospital-based, retrospective cohort study, conducted at 109 centres in five continents, including women harbouring germline BRCA1, BRCA2, or both, pathogenic or likely pathogenic variants and diagnosed with stage I-III invasive breast cancer at the age of 40 years or younger between Jan 1, 2000, and Dec 31, 2020. The primary objectives of the present analysis were to determine the association between RRM or RRSO and overall survival in young BRCA carriers with breast cancer. The primary endpoint was overall survival. This study is registered with ClinicalTrials.gov, NCT03673306.
FINDINGS
Between Jan 1, 2000 and Dec 31, 2020, 5290 patients were included, of whom 3361 (63·5%) patients were BRCA1 pathogenic variant carriers, 2708 (51·2%) had node-negative, and 2421 (45·8%) hormone receptor-positive breast cancer. Of 5290 patients, 2910 (55·0%) underwent RRM, 2782 (52·6%) underwent RRSO. After a median follow-up of 8·2 years (IQR 4·7-12·8), RRM was associated with significantly better overall survival compared with no RRM (adjusted HR [aHR] 0·65, 95% CI 0·53-0·78; 20-year restricted mean overall survival time 17·89 years [95% CI 17·61-18·17] with RRM vs 16·65 years [16·38-16·92] without RRM). RRSO was also associated with significantly better overall survival compared with no RRSO (aHR 0·58, 95% CI 0·48-0·71; 20-year restricted mean overall survival time 17·73 years [95% CI 17·43-18·03] with RRSO vs 16·67 years [16·38-16·96] without RRSO).
INTERPRETATION
In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, RRM and RRSO were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counselling of a unique and high-risk patient population on cancer risk management strategies.
FUNDING
Italian Association for Cancer Research.
背景
关于降低风险手术对既往有乳腺癌病史的年轻BRCA基因携带者的影响，现有证据较少。我们在一个全球大型既往有乳腺癌的年轻BRCA基因携带者队列中，研究了降低风险的乳房切除术（RRM）或降低风险的输卵管卵巢切除术（RRSO）或两者联合与生存结局之间的关联。
方法
BRCA BCY合作研究是一项基于医院的国际回顾性队列研究，在五大洲的109个中心开展，纳入携带种系BRCA1、BRCA2或两者的致病性或可能致病性变异、并在2000年1月1日至2020年12月31日期间40岁及以下被诊断为I-III期浸润性乳腺癌的女性。本分析的主要目的是确定RRM或RRSO与既往有乳腺癌的年轻BRCA基因携带者总生存之间的关联。主要终点是总生存。本研究已在ClinicalTrials.gov注册，注册号为NCT03673306。
研究结果
2000年1月1日至2020年12月31日期间，共纳入5290例患者，其中3361例（63.5%）为BRCA1致病性变异携带者，2708例（51.2%）为淋巴结阴性，2421例（45.8%）为激素受体阳性乳腺癌。在5290例患者中，2910例（55.0%）接受了RRM，2782例（52.6%）接受了RRSO。中位随访8.2年（四分位间距4.7-12.8年）后，与未行RRM相比，RRM与显著更好的总生存相关（校正风险比[aHR]0.65，95%置信区间0.53-0.78；20年受限平均总生存时间，RRM组为17.89年[95%置信区间17.61-18.17]，未行RRM组为16.65年[16.38-16.92]）。与未行RRSO相比，RRSO也与显著更好的总生存相关（aHR 0.58，95%置信区间0.48-0.71；20年受限平均总生存时间，RRSO组为17.73年[95%置信区间17.43-18.03]，未行RRSO组为16.67年[16.38-16.96]）。
解读
在这个全球既往年轻时被诊断为乳腺癌的BRCA基因携带者队列中，RRM和RRSO均与总生存的显著改善相关。这些发现为针对独特的高危患者群体进行癌症风险管理策略的个性化咨询提供了证据。
资助
意大利癌症研究协会
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