Rebbeck T R, Levin A M, Eisen A, Snyder C, Watson P, Cannon-Albright L, Isaacs C, Olopade O, Garber J E, Godwin A K, Daly M B, Narod S A, Neuhausen S L, Lynch H T, Weber B L
T. R. Rebbeck, A. Eisen, B. L. Weber, Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
J Natl Cancer Inst. 1999 Sep 1;91(17):1475-9. doi: 10.1093/jnci/91.17.1475.
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.
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 year of birth.
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.
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.
BRCA1基因遗传性突变的基因检测可为患乳腺癌或卵巢癌风险较高的女性提供潜在的有价值信息；然而，BRCA1突变携带者降低癌症风险的临床管理选择很少。双侧预防性卵巢切除术（即手术切除卵巢）后卵巢激素暴露的减少可能会改变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突变携带者患乳腺癌风险的降低相关。
我们研究了一组从北美五个中心收集的患有与疾病相关的种系BRCA1突变的女性。手术组（n = 43）包括患有BRCA1突变且接受了双侧预防性卵巢切除术但无乳腺癌或卵巢癌病史且未进行预防性乳房切除术的女性。对照组包括无卵巢切除术病史且无乳腺癌或卵巢癌病史的BRCA1突变女性（n = 79）。根据中心和出生年份将对照组与手术组进行匹配。
我们发现双侧预防性卵巢切除术后乳腺癌风险有统计学意义的降低，调整后的风险比（HR）为0.53（95%置信区间[CI] = 0.33 - 0.84）。在手术后随访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，这种风险降低更为明显。使用激素替代疗法并未消除手术后乳腺癌风险的降低。
双侧预防性卵巢切除术与携带BRCA1突变的女性患乳腺癌风险降低相关。可能的机制是卵巢激素暴露的减少。这些发现对携带BRCA1突变的女性乳腺癌风险管理具有重要意义。
