Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers
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DOI：
10.1001/jama.2017.7112
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发表时间：
2017-06-20
影响因子：
120.7
通讯作者：
Antoniou, Antonis C.
中科院分区：
文献类型：
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作者：
Kuchenbaecker, Karoline B.;Hopper, John L.;Antoniou, Antonis C.
重要性 BRCA1 和 BRCA2 突变携带者的临床管理需要准确、前瞻性的癌症风险评估。 目的 评估突变携带者患乳腺癌、卵巢癌和对侧乳腺癌的特定年龄风险，并评估家族癌症史和突变位置的风险修正。 设计、设置和参与者 对 6036 名 BRCA1 和 3820 名 BRCA2 女性携带者（5046 名未受影响和 5046 名未受影响的女性）进行前瞻性队列研究 4810 名基线患有乳腺癌或卵巢癌或两者均患有乳腺癌或卵巢癌的患者）于 1997 年至 2011 年通过国际 BRCA1/2 携带者队列研究、乳腺癌家族登记处和凯瑟琳·坎宁安基金会家族性乳腺癌研究联盟招募，并通过家庭诊所 (94%) 和基于人群的研究 (6%) 进行确定。大多数来自英国 (EMBRACE)、荷兰 (HEBON) 和法国 (GENEPSO) 的大型国家研究。后续行动截至2013年12月；中位随访时间为 5 年。暴露 BRCA1/2 突变、家族癌症史和突变位置。主要结果和测量乳腺癌、卵巢癌和对侧乳腺癌的年发病率、标准化发病率和累积风险。结果 在符合乳腺癌分析资格的 3886 名女性（中位年龄 38 岁；四分位数范围 [IQR]，30-46 岁）中，有 5066 名女性 符合卵巢癌分析条件的女性（中位年龄 38 岁；IQR，31-47 岁）和符合对侧乳腺癌分析条件的 2213 名女性（中位年龄 47 岁；IQR，40-55 岁）在随访期间诊断出乳腺癌 426 例，卵巢癌 109 例，对侧乳腺癌 245 例。 BRCA1 携带者到 80 岁的累积乳腺癌风险为 72%（95% CI，65%-79%），BRCA2 携带者为 69%（95% CI，61%-77%）。乳腺癌发病率在成年早期迅速增加，直到 30 至 40 岁（BRCA1 携带者）和 40 至 50 岁（BRCA2 携带者），然后保持相似的恒定发病率（每 1000 人年 20-30 人），直到 80 岁。 BRCA1 携带者到 80 岁的累积卵巢癌风险为 44%（95% CI，36%-53%），BRCA2 携带者为 17%（95% CI，11%-25%）。对于对侧乳腺癌，乳腺癌诊断后 20 年，BRCA1 携带者的累积风险为 40%（95% CI，35%-45%），BRCA2 携带者为 26%（95% CI，20%-33%）（比较 BRCA2 与 BRCA1 的风险比 [HR]，0.62；95% CI，0.47-0.82；差异 P=.001）。随着被诊断为同时患有 BRCA1 乳腺癌的一级和二级亲属数量增加，患乳腺癌的风险也会增加（>= 2 与 0 受影响亲属的 HR，1.99；95% CI，1.41-2.82；P
IMPORTANCE The clinical management of BRCA1 and BRCA2 mutation carriers requires accurate, prospective cancer risk estimates.OBJECTIVES To estimate age-specific risks of breast, ovarian, and contralateral breast cancer for mutation carriers and to evaluate risk modification by family cancer history and mutation location.DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 6036 BRCA1 and 3820 BRCA2 female carriers (5046 unaffected and 4810 with breast or ovarian cancer or both at baseline) recruited in 1997-2011 through the International BRCA1/2 Carrier Cohort Study, the Breast Cancer Family Registry and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, with ascertainment through family clinics (94%) and population-based studies (6%). The majority were from large national studies in the United Kingdom (EMBRACE), the Netherlands (HEBON), and France (GENEPSO). Follow-up ended December 2013; median follow-up was 5 years.EXPOSURES BRCA1/2 mutations, family cancer history, and mutation location.MAIN OUTCOMES AND MEASURES Annual incidences, standardized incidence ratios, and cumulative risks of breast, ovarian, and contralateral breast cancer.RESULTS Among 3886 women (median age, 38 years; interquartile range [IQR], 30-46 years) eligible for the breast cancer analysis, 5066 women (median age, 38 years; IQR, 31-47 years) eligible for the ovarian cancer analysis, and 2213 women (median age, 47 years; IQR, 40-55 years) eligible for the contralateral breast cancer analysis, 426 were diagnosed with breast cancer, 109 with ovarian cancer, and 245 with contralateral breast cancer during follow-up. The cumulative breast cancer risk to age 80 years was 72%(95% CI, 65%-79%) for BRCA1 and 69%(95% CI, 61%-77%) for BRCA2 carriers. Breast cancer incidences increased rapidly in early adulthood until ages 30 to 40 years for BRCA1 and until ages 40 to 50 years for BRCA2 carriers, then remained at a similar, constant incidence (20-30 per 1000 person-years) until age 80 years. The cumulative ovarian cancer risk to age 80 years was 44%(95% CI, 36%-53%) for BRCA1 and 17%(95% CI, 11%-25%) for BRCA2 carriers. For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95% CI, 35%-45%) for BRCA1 and 26%(95% CI, 20%-33%) for BRCA2 carriers (hazard ratio [HR] for comparing BRCA2 vs BRCA1, 0.62; 95% CI, 0.47-0.82; P=.001 for difference). Breast cancer risk increased with increasing number of first-and second-degree relatives diagnosed as having breast cancer for both BRCA1 (HR for >= 2 vs 0 affected relatives, 1.99; 95% CI, 1.41-2.82; P