Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers
Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers
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DOI：
10.1093/jnci/91.17.1475
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发表时间：
1999-09-01
影响因子：
10.3
通讯作者：
Weber, BL
中科院分区：
文献类型：
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作者：
Rebbeck, TR;Levin, AM;Weber, BL
背景：BRCA1基因遗传突变基因检测的可用性为乳腺癌或卵巢癌高风险妇女提供了潜在的有价值的信息；然而，BRCA1突变携带者很少有临床管理选择来降低他们的癌症风险。双侧预防性卵巢切除术（即手术切除卵巢）后卵巢激素暴露减少可能改变BRCA1突变携带者的癌症风险。本研究旨在评估双侧预防性卵巢切除术是否与BRCA1突变携带者乳腺癌风险降低相关。方法：我们研究了来自北美五个中心的携带疾病相关种系BRCA1突变的女性队列。手术对象（n 43）包括BRCA1突变的女性，她们接受了双侧预防性卵巢切除术，但没有乳腺癌或卵巢癌病史，也没有做过预防性乳房切除术。对照组包括无卵巢切除术史、无乳腺癌或卵巢癌史的BRCA1突变女性（n = 79）。对照组与手术组按出生中心、出生年轮进行匹配。结果：我们发现双侧预防性卵巢切除术后乳腺癌风险显著降低，校正风险比（HR）为0.53（95%可信区间[CI] = 0.33-0.84）。在术后随访5-10年（HR = 0.28; 95% CI = 0.08-0.94）或至少10年（HR = 0.33; 95% CI = 0.12-0.91）的女性中，这种风险降低幅度更大。使用激素替代疗法并没有抵消手术后乳腺癌风险的降低。结论：双侧预防性卵巢切除术与携带BRCA1突变的女性乳腺癌风险降低相关。可能的机制是卵巢激素暴露减少。这些发现对携带BRCA1突变的女性的乳腺癌风险管理具有启示意义。
Background: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. Methods: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and gear of birth. Results: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. Conclusions: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.