Ian M. Collins, Sue Anne McLachlan, Prue Weideman, Kate E. Birch, and Kelly-Anne Phillips, Peter MacCallum Cancer Centre; Ian M. Collins, Roger L. Milne, Sue Anne McLachlan, Martha Hickey, John L. Hopper, and Kelly-Anne Phillips, University of Melbourne; Sue Anne McLachlan, St Vincent's Hospital; Martha Hickey, Royal Women's Hospital, Parkville, Melbourne; Michael Friedlander, Prince of Wales Hospital, Sydney, Australia; and John L. Hopper, Seoul National University, Seoul, Republic of Korea.
J Clin Oncol. 2013 Nov 1;31(31):3920-5. doi: 10.1200/JCO.2013.49.3007. Epub 2013 Sep 30.
Limited data suggest that germline BRCA1 mutations are associated with occult primary ovarian insufficiency and that BRCA1 and BRCA2 mutation carriers might have earlier natural menopause (NM) than their noncarrier relatives.
Eligible women were mutation carriers and noncarriers from families segregating a BRCA1 or BRCA2 mutation. Data were self-reported using uniform questionnaires at cohort entry and every 3 years thereafter. NM was defined as the cessation of menses for 12 months without another cause. Cox proportional hazards analysis modeled time from birth to NM, adjusting for multiple potential confounders. Analysis time was censored at the earliest of the following: last follow-up, bilateral oophorectomy, hysterectomy, commencement of hormone therapy, insertion of intrauterine device, or any cancer diagnosis. Hazard ratios (HRs) were estimated as a measure of how likely mutation carriers are, relative to noncarriers, to reach NM at a given age.
A total of 1,840 women were eligible for analysis. Overall only 19% reached NM. A lower proportion of BRCA1 and BRCA2 mutation carriers reached NM compared with noncarriers. Conversely, a higher proportion of mutation carriers were censored at cancer diagnosis or oophorectomy than noncarriers. The adjusted HR estimates for NM were 1.03 (95% CI, 0.75 to 1.40; P = .9) for 445 BRCA1 mutation carriers and 559 noncarrier relatives and 1.01 (95% CI, 0.71 to 1.42; P = .9) for 374 BRCA2 mutation carriers and 462 noncarrier relatives.
We found no evidence that BRCA1 and BRCA2 mutation carriers are at higher risk of NM at a given age than their noncarrier relatives.
有限的数据表明，BRCA1 种系突变与隐匿性原发性卵巢功能不全相关，并且 BRCA1 和 BRCA2 突变携带者可能比非携带者亲属更早进入自然绝经（NM）。
合格的女性是来自于携带 BRCA1 或 BRCA2 突变的家族的突变携带者和非携带者。数据通过在队列入组时和之后每 3 年使用统一的问卷进行自我报告。NM 定义为停经 12 个月且无其他原因。使用 Cox 比例风险分析模型来对从出生到 NM 的时间进行建模，同时调整了多个潜在混杂因素。分析时间截止于以下最早的事件：最后一次随访、双侧卵巢切除术、子宫切除术、激素治疗开始、宫内节育器插入或任何癌症诊断。风险比（HR）用于衡量突变携带者相对于非携带者在特定年龄达到 NM 的可能性。
共有 1840 名女性符合分析条件。总体而言，只有 19%的人达到 NM。BRCA1 和 BRCA2 突变携带者达到 NM 的比例低于非携带者。相反，与非携带者相比，更多的突变携带者因癌症诊断或卵巢切除术而被删失。调整后的 NM 风险比估计值为 1.03（95%CI，0.75 至 1.40；P=0.9），对于 445 名 BRCA1 突变携带者和 559 名非携带者亲属；以及 1.01（95%CI，0.71 至 1.42；P=0.9），对于 374 名 BRCA2 突变携带者和 462 名非携带者亲属。
我们没有发现证据表明 BRCA1 和 BRCA2 突变携带者在特定年龄时 NM 的风险高于其非携带者亲属。
