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Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers.
Breast Cancer Research ( IF 6.1 ) Pub Date : 2020-01-16 , DOI: 10.1186/s13058-020-1247-4 Nasim Mavaddat 1 , Antonis C Antoniou 1 , Thea M Mooij 2 , Maartje J Hooning 3 , Bernadette A Heemskerk-Gerritsen 3 , , Catherine Noguès 4 , Marion Gauthier-Villars 5 , Olivier Caron 6 , Paul Gesta 7 , Pascal Pujol 8 , Alain Lortholary 9 , , Daniel Barrowdale 1 , Debra Frost 1 , D Gareth Evans 10 , Louise Izatt 11 , Julian Adlard 12 , Ros Eeles 13 , Carole Brewer 14 , Marc Tischkowitz 15 , Alex Henderson 16 , Jackie Cook 17 , Diana Eccles 18 , , Klaartje van Engelen 19 , Marian J E Mourits 20 , Margreet G E M Ausems 21 , Linetta B Koppert 22 , John L Hopper 23 , Esther M John 24 , Wendy K Chung 25, 26 , Irene L Andrulis 27, 28 , Mary B Daly 29 , Saundra S Buys 30 , , Javier Benitez 31 , Trinidad Caldes 32 , Anna Jakubowska 33, 34 , Jacques Simard 35 , Christian F Singer 36 , Yen Tan 36 , Edith Olah 37 , Marie Navratilova 38 , Lenka Foretova 38 , Anne-Marie Gerdes 39 , Marie-José Roos-Blom 2 , Flora E Van Leeuwen 2 , Brita Arver 40, 41 , Håkan Olsson 41 , Rita K Schmutzler 42, 43 , Christoph Engel 44 , Karin Kast 45, 46, 47 , Kelly-Anne Phillips 23, 48, 49 , Mary Beth Terry 26, 50 , Roger L Milne 23, 51, 52 , David E Goldgar 53 , Matti A Rookus 2 , Nadine Andrieu 54, 55, 56, 57 , Douglas F Easton 1, 58 , , ,
Breast Cancer Research ( IF 6.1 ) Pub Date : 2020-01-16 , DOI: 10.1186/s13058-020-1247-4 Nasim Mavaddat 1 , Antonis C Antoniou 1 , Thea M Mooij 2 , Maartje J Hooning 3 , Bernadette A Heemskerk-Gerritsen 3 , , Catherine Noguès 4 , Marion Gauthier-Villars 5 , Olivier Caron 6 , Paul Gesta 7 , Pascal Pujol 8 , Alain Lortholary 9 , , Daniel Barrowdale 1 , Debra Frost 1 , D Gareth Evans 10 , Louise Izatt 11 , Julian Adlard 12 , Ros Eeles 13 , Carole Brewer 14 , Marc Tischkowitz 15 , Alex Henderson 16 , Jackie Cook 17 , Diana Eccles 18 , , Klaartje van Engelen 19 , Marian J E Mourits 20 , Margreet G E M Ausems 21 , Linetta B Koppert 22 , John L Hopper 23 , Esther M John 24 , Wendy K Chung 25, 26 , Irene L Andrulis 27, 28 , Mary B Daly 29 , Saundra S Buys 30 , , Javier Benitez 31 , Trinidad Caldes 32 , Anna Jakubowska 33, 34 , Jacques Simard 35 , Christian F Singer 36 , Yen Tan 36 , Edith Olah 37 , Marie Navratilova 38 , Lenka Foretova 38 , Anne-Marie Gerdes 39 , Marie-José Roos-Blom 2 , Flora E Van Leeuwen 2 , Brita Arver 40, 41 , Håkan Olsson 41 , Rita K Schmutzler 42, 43 , Christoph Engel 44 , Karin Kast 45, 46, 47 , Kelly-Anne Phillips 23, 48, 49 , Mary Beth Terry 26, 50 , Roger L Milne 23, 51, 52 , David E Goldgar 53 , Matti A Rookus 2 , Nadine Andrieu 54, 55, 56, 57 , Douglas F Easton 1, 58 , , ,
Affiliation
BACKGROUND
The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.
METHODS
A multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.
RESULTS
There was no association between RRSO and breast cancer for BRCA1 (HR = 1.23; 95% CI 0.94-1.61) or BRCA2 (HR = 0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45 years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.
CONCLUSION
We found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
中文翻译：
降低输卵管卵巢切除术、自然绝经和乳腺癌风险的风险：BRCA1 和 BRCA2 突变携带者的国际前瞻性队列。
背景 降低风险的输卵管卵巢切除术 (RRSO) 对 BRCA1 和 BRCA2 突变携带者患乳腺癌风险的影响尚不确定。回顾性分析表明有保护作用，但可能存在很大偏差。前瞻性研究的效力有限，特别是对于 BRCA2 突变携带者。此外，之前的研究并未考虑 RRSO 在自然绝经背景下的影响。方法 对 2272 名 BRCA1 和 1605 名 BRCA2 突变携带者组成的多中心前瞻性队列进行随访，平均随访时间分别为 5.4 年和 4.9 年。 426 名女性罹患乳腺癌。 RRSO 在 Cox 回归中被建模为时间依赖性协变量，并在绝经前和绝经后女性中评估其效果。结果 对于 BRCA1（HR = 1.23；95% CI 0.94-1.61）或 BRCA2（HR = 0.88；95% CI 0.62-1.24）突变携带者，RRSO 与乳腺癌之间没有关联。对于 BRCA2 突变携带者，45 岁之前或之后进行的 RRSO 的 HR 分别为 0.68 (95% CI 0.40-1.15) 和 1.07 (95% CI 0.69-1.64)。 BRCA2 突变携带者的 HR 随着 RRSO 后时间的增加而降低（RRSO 后 5 年或更长时间，HR = 0.51；95% CI 0.26-0.99）。对绝经前女性的估计也相似。结论 我们没有发现任何证据表明 RRSO 可以降低 BRCA1 突变携带者患乳腺癌的风险。观察到对 BRCA2 突变携带者的潜在有益影响，特别是在 RRSO 5 年后。这些结果可为运营商提供有关 RRSO 的咨询和管理信息。
更新日期：2020-04-22
中文翻译：
降低输卵管卵巢切除术、自然绝经和乳腺癌风险的风险：BRCA1 和 BRCA2 突变携带者的国际前瞻性队列。
背景 降低风险的输卵管卵巢切除术 (RRSO) 对 BRCA1 和 BRCA2 突变携带者患乳腺癌风险的影响尚不确定。回顾性分析表明有保护作用，但可能存在很大偏差。前瞻性研究的效力有限，特别是对于 BRCA2 突变携带者。此外，之前的研究并未考虑 RRSO 在自然绝经背景下的影响。方法 对 2272 名 BRCA1 和 1605 名 BRCA2 突变携带者组成的多中心前瞻性队列进行随访，平均随访时间分别为 5.4 年和 4.9 年。 426 名女性罹患乳腺癌。 RRSO 在 Cox 回归中被建模为时间依赖性协变量，并在绝经前和绝经后女性中评估其效果。结果 对于 BRCA1（HR = 1.23；95% CI 0.94-1.61）或 BRCA2（HR = 0.88；95% CI 0.62-1.24）突变携带者，RRSO 与乳腺癌之间没有关联。对于 BRCA2 突变携带者，45 岁之前或之后进行的 RRSO 的 HR 分别为 0.68 (95% CI 0.40-1.15) 和 1.07 (95% CI 0.69-1.64)。 BRCA2 突变携带者的 HR 随着 RRSO 后时间的增加而降低（RRSO 后 5 年或更长时间，HR = 0.51；95% CI 0.26-0.99）。对绝经前女性的估计也相似。结论 我们没有发现任何证据表明 RRSO 可以降低 BRCA1 突变携带者患乳腺癌的风险。观察到对 BRCA2 突变携带者的潜在有益影响，特别是在 RRSO 5 年后。这些结果可为运营商提供有关 RRSO 的咨询和管理信息。
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