Shu Catherine A, Pike Malcolm C, Jotwani Anjali R, Friebel Tara M, Soslow Robert A, Levine Douglas A, Nathanson Katherine L, Konner Jason A, Arnold Angela G, Bogomolniy Faina, Dao Fanny, Olvera Narciso, Bancroft Elizabeth K, Goldfrank Deborah J, Stadler Zsofia K, Robson Mark E, Brown Carol L, Leitao Mario M, Abu-Rustum Nadeem R, Aghajanian Carol A, Blum Joanne L, Neuhausen Susan L, Garber Judy E, Daly Mary B, Isaacs Claudine, Eeles Rosalind A, Ganz Patricia A, Barakat Richard R, Offit Kenneth, Domchek Susan M, Rebbeck Timothy R, Kauff Noah D
Division of Hematology-Oncology, Columbia University Medical Center, New York, New York.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
JAMA Oncol. 2016 Nov 1;2(11):1434-1440. doi: 10.1001/jamaoncol.2016.1820.
The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial.
To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression.
Incidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database.
Among the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors.
Although the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.
BRCA突变与子宫癌之间的联系尚不清楚。因此，尽管降低风险的输卵管卵巢切除术（RRSO）是BRCA突变女性（BRCA+女性）的标准治疗方法，但同时进行子宫切除术的作用仍存在争议。
确定未行子宫切除术的RRSO术后BRCA+女性患子宫癌的风险及特定组织学亚型的分布情况。
设计、设置和参与者：这项多中心前瞻性队列研究纳入了1995年1月1日至2011年12月31日期间在美国和英国的9个学术医疗中心确诊为有害BRCA1或BRCA2突变且未进行过子宫切除术或同期未行子宫切除术的1083名女性。其中，627名参与者为BRCA1+；453名，BRCA2+；3名，两者皆有。参与者在确诊、BRCA检测或RRSO（以最后发生者为准）后进行了中位时间为5.1年（四分位间距[IQR]，3.0 - 8.4年）的前瞻性随访。分析纳入了截至2014年10月14日的随访数据。在子宫癌诊断、子宫切除术、最后一次随访或死亡时进行截尾。新癌症按组织学亚型分类，并对可用肿瘤进行野生型BRCA基因缺失和/或蛋白表达分析。
未行子宫切除术的RRSO术后BRCA+女性子宫体癌的发病率与监测、流行病学和最终结果数据库预期发病率的比较。
在1083名未行子宫切除术的RRSO术后女性中，中位年龄为45.6岁（IQR：40.9 - 52.5），观察到8例子宫癌（预期4.3例；观察值与预期值[O:E]之比为1.9；95%CI，0.8 - 3.7；P = 0.09）。按亚型分层后，未发现子宫内膜样腺癌或肉瘤风险增加。RRSO术后7.2至12.9年观察到5例浆液性和/或浆液样（浆液/浆液样）子宫内膜癌（4例BRCA1+和1例BRCA2+）（BRCA1：预期0.18例[O:E比，22.2；95%CI，6.1 - 56.9；P < 0.001]；BRCA2：预期0.16例[O:E比，6.4；95%CI，0.2 - 35.5；P = 0.15]）。肿瘤分析证实所有3例可用的浆液/浆液样BRCA1+肿瘤中野生型BRCA1基因和/或蛋白表达缺失。
尽管RRSO术后子宫癌的总体风险未增加，但BRCA1+女性浆液/浆液样子宫内膜癌的风险增加。在讨论BRCA1+女性RRSO时子宫切除术的利弊时应考虑到这一风险。
