Clinical and pathologic findings of prophylactic salpingo-oophorectomies in 159 BRCA1 and BRCA2 carriers
Introduction
The lifetime risks of ovarian cancer for women who carry a BRCA1 or BRCA2 mutation range from 16 to 54% [1], [2], [3]. These women comprise the population at highest known risk for ovarian cancer. In contrast, women in the general population of the USA have a 1.7% chance of developing ovarian cancer over their lifetime [4]. The limitations of current screening techniques, and the typical late stage at presentation of ovarian cancer contribute to the high case fatality rate. In the absence of effective strategies to reduce mortality from ovarian cancer by early detection, primary risk reduction through oral contraceptive use and prophylactic surgery is appropriate for this high risk population.
Women who carry a BRCA1 or BRCA2 mutation are often advised to consider prophylactic bilateral salpingo-oophorectomy (prophylactic oophorectomy) after age 35, or after childbearing is complete [5]. This procedure is thought to reduce the risk of ovarian cancer substantially in these women and to reduce the risk of breast cancer if performed prior to menopause due to decreased circulating estrogen [6], [7]. However, there are wide-ranging implications of this surgery for a woman's well-being, particularly for women who elect to have surgery prior to menopause.
We previously described a series of 60 carriers women who underwent prophylactic oophorectomy for increased risk of ovarian cancer, of whom 27 had a BRCA1 mutation and 12 carried a BRCA2 mutation [8]. Occult carcinoma was found in five of the 39 mutation carriers (13%). Interestingly, all five occult carcinomas were found in BRCA1 mutation carriers and four of the five were not detectable on gross examination. None had been identified through screening. We have now extended this series to include 159 BRCA1 and BRCA2 mutation carriers undergoing prophylactic oophorectomy over a 12-year period.
Section snippets
Materials and methods
Women in this study are at high risk for ovarian cancer based on known BRCA1 or BRCA2 mutation carrier status. Each underwent prophylactic oophorectomy at the University Health Network between January 1, 1992 and June 2004. Table 1 summarizes the mutation status (BRCA1 or BRCA2) and age at prophylactic oophorectomy for all 159 subjects. A small number of women in this series underwent prophylactic oophorectomy prior to the identification of the BRCA1 or BRCA2 mutation in their family (i.e. high
Results
From January 1992 until June 2004, 159 women with a known BRCA1 or BRCA2 mutation underwent prophylactic oophorectomy at the University Health Network. The mean age at the time of surgery was 47.7 years (range 34–71). Ninety-four of the 159 (59.1%) subjects carry a BRCA1 mutation and 65 of 159 (40.9%) have a BRCA2 mutation. At the time of surgery, the average age of the BRCA1 carriers was 47.0 years and the average age of the BRCA2 carriers was 48.8 years. Most were pre- or peri-menopausal
Case 1
A grossly identifiable 5 cm mass was attached to the tubal fimbria by a pedicle, without attachment to the ipsilateral ovary. The tumor was a poorly differentiated serous carcinoma with a predominant solid architecture. Two microscopic foci of invasive serous carcinoma were also present, one within the cortex of the ipsilateral ovary and one identified in a peritoneal biopsy.
Case 2
A microscopic focus of high-grade serous carcinoma measuring less than 1 mm was found on the surface of one ovary.
Screening examinations
Six of the seven women with occult cancer had either an ultrasound or CA125 blood test or both within 9 months prior to surgery (see Table 3). Five of these six had a normal ultrasound within 9 months of surgery. One of the six subjects had a right adnexal hypoechoic lesion that had remained stable since an ultrasound five months earlier and had not been considered suspicious. Though this subject had a CA125 level of 39 (Normal< = 35) 10 months prior to surgery, her CA125 levels were normal 1
Discussion
This study included all women with BRCA1 or BRCA2 undergoing prophylactic oophorectomy specimens from carriers over a 12.5-year period, and is one of the largest series reported to date. Each specimen was thoroughly examined, and we have included both grossly visible and occult cancers in our prevalence rate. The prevalence of cancers in this series of patients (4.4%) is lower than what we previously reported (Colgan et al.) (12.8%) and is similar to the prevalence reported by Rebbeck et al.
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2021, MaturitasCitation Excerpt :In premenopausal, hormone-sensitive breast cancer patients, an ovariectomy is also performed more easily for therapeutic oncologic purposes than inducing pharmacological menopause. The increased access to RRSO in breast cancer survivors has never been clearly reported before [13–24]. In the present study, the prevalence of BRCA mutations carriers undergoing RRSO that were breast cancer survivors is higher than observed in a previous study [12].