宾夕法尼亚大学Abramson癌症中心的Susan M. Domchek博士在美国临床肿瘤学会(ASCO)年会上公布的一项观察性队列研究显示，有BRCA突变并接受了预防性卵巢切除术的女性仍可通过激素替代治疗(HRT)控制围绝经期症状，至少短期治疗不增加乳腺癌风险。
这项名为“外科终点的预防和观察(PROSE)”的研究从美国和欧洲20个中心招募了1,299例存在BRCA1突变(61%)或BRCA2突变(39%)的女性患者，其中25%接受了预防性输卵管-卵巢切除术，后者中45%术后接受HRT。对未曾接受卵巢切除术和HRT的女性平均随访5.1年，对接受手术但未曾接受HRT者平均随访3.6年，对接受手术和HRT者平均随访5.4年。
结果显示，共有22%的受试者被诊断为乳腺癌，而在接受了卵巢切除术的亚组中这一比例仅为13%。分析表明，术后HRT并未导致乳腺癌风险增加，反而呈风险下降的趋势：与术后未接受HRT者相比，风险比(HR)为0.78；与未接受手术和HRT者相比，HR为0.43。上述结果不受BRCA突变亚型或具体HRT用药种类的影响。
此外，在未接受卵巢切除术的女性中，曾在自然绝经后使用过HRT药物者的乳腺癌风险也倾向于降低(HR，0.52)。
但梅奥医院的肿瘤学家Lynn Hartmann博士评论指出，需警惕这项观察性研究中的潜在偏倚：家人中BRCA突变所致癌症的类型可能影响女性对卵巢切除术的选择，乳腺病史(如不典型增生)可能影响术后对HRT的选择，等等。她建议开展大规模、多中心注册研究，以得出更确切的结论。
生物探索推荐英文原文
DOI: 10.1200/JCO.2007.13.9626
Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated
Breast and Gynecologic Cancer: A Multicenter, Prospective Study
Abstract: Purpose Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers.
Patients and Methods A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model.
Results During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance.
Conclusion The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.
