The connection between BRCA mutations and uterine cancer is unknown. As a result, while risk-reducing salpingo-oophorectomy (RRSO) is the conventional therapy for women with BRCA mutations (BRCA+ women), the significance of concurrent hysterectomy remains debatable. The purpose of this study was to look at the risk of uterine cancer and the distribution of certain histologic subtypes in BRCA+ women who had RRSO without hysterectomy.

 

This multicenter prospective cohort study included 1083 women who underwent RRSO without a prior or concomitant hysterectomy and had a deleterious BRCA1 or BRCA2 mutation identified between January 1, 1995, and December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom. There were 627 BRCA1+ individuals, 453 BRCA2+ people, and 3 both. Participants were followed up on for a median of 5.1 (interquartile range [IQR], 3.0-8.4) years following diagnosis, BRCA testing, or RRSO (whichever occurred last). The analysis included follow-up data accessible through October 14, 2014. Censoring took place at the time of uterine cancer diagnosis, hysterectomy, last follow-up, or death. New malignancies were classified according to their histologic subtype, and existing tumors were examined for deletion of the wild-type BRCA gene and/or protein expression. The incidence of uterine corpus cancer in BRCA+ women who had RRSO without hysterectomy as compared to the rates predicted by the Surveillance, Epidemiology, and End Results database.

 

At a median age of 45.6 (IQR: 40.9 – 52.5), 8 incident uterine malignancies were identified among the 1083 women who received RRSO without hysterectomy (4.3 anticipated; observed to expected [O: E] ratio, 1.9; 95% CI, 0.8-3.7; P =.09). After stratifying by subtype, there was no increased incidence of endometrioid endometrial cancer or sarcoma. Five serious and/or serous-like endometrial carcinomas (4 BRCA1+ and 1 BRCA2+) were found 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 investigations revealed that the wild-type BRCA1 gene and/or protein expression was lost in all three available serous/serous-like BRCA1+ cancers.

Reference:jamanetwork.com/journals/jamaoncology/fullarticle/2531470?resultClick=1

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