Bilateral oophorectomy and breast cancer risk reduction among women with a family history☆
Introduction
Estrogens are clearly implicated in the pathogenesis of breast cancer [1]. Removal of the ovaries has been shown to reduce risk of breast cancer in several [2], [3], [4], [5], but not all [6] studies. However, the benefit of this procedure for women with familial risk is not well established. Three independent studies have examined the association of oophorectomy and breast cancer among high-risk women. The first study included members of 12 high-risk cancer families and noted that the observed/expected ratio for breast cancer was 2.7-fold greater than the general population among oophorectomized family members, but seven-fold greater among non-oophorectomized family members [7]. Rebbeck et al. [8] investigated the association of oophorectomy with breast cancer risk among 99 oophorectomized BRCA1 or BRCA2 mutation carriers matched on year of birth (±5 years), treatment center and type of mutation (BRCA1 or BRCA2) to 142 female mutation carriers who did not have oophorectomy. Overall results after at least 8 years of follow-up suggest an approximate 50% reduction in risk of breast cancer after bilateral oophorectomy. The second study of the breast cancer risk reduction among carriers of mutations in BRCA1 and BRCA2 was conducted by Kauff et al. [9] among 170 women with known mutations. Ninety-eight elected to undergo oophorectomy, 72 opted for surveillance. After a mean of 22.6 months of follow-up, those who chose oophorectomy were at approximately 1/3 the risk of breast cancer compared to those who opted for surveillance (HR=0.32; 0.08–1.2). These figures were unadjusted for important covariates, including use of hormone therapy or other known breast cancer risk factors. Although these studies are consistent in their evidence for oophorectomy and cancer risk reduction, each was based on a small sample within a specialized populations. Since many women who are at high risk of breast and ovarian cancer for cancer risk reduction are hesitant to undergo genetic testing because of insurance discrimination [10], [11], we sought to estimate the potential risk reduction of oophorectomy among women with a family history of breast cancer but unknown BRCA1/2 status.
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Patients and methods
Women less than age 60 with possible bilateral oophorectomy during 1970–1994 were identified from the Mayo Clinic Surgical Index. A random selection of charts (n=2272) was reviewed from all even-numbered years until at least 50 eligible women were identified from each year. Based on data in the medical records, we excluded women who: (1) had only one ovary removed (n=335) or had just a hysterectomy (n=694) on the date selected; or (2) had evidence of any history of cancer prior to surgery,
Results
Of 851 eligible women, data were collected on 680 (80%); 35 (5%) through next-of-kin surrogates. Overall, 7% refused, 2% were deceased with no surrogate available, and 11% could not be located or were unable to participate. Based on the survey data, 46 reported having had cancer prior to the date of their bilateral oophorectomy. These women were excluded, leaving 634 women available for analyses (see Table 1 for description of respondents).
Table 2 includes the expected and observed number of
Discussion
Many women who meet with medical genetics professionals (Medical Geneticists or Genetic Counselors) eventually decide not to proceed with mutation testing for BRCA1 or BRCA2 [11]. This study was designed to quantify the risk reduction from oophorectomy among women who have been categorized into risk groupings solely on the basis of their family history. Our results suggest that oophorectomy is just as effective in reducing risk of breast cancer among women with a family history as has been
Acknowledgements
This work was supported by a grant from the Fraternal Order of the Eagles and by the National Cancer Institute, grant CA82267.
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Presented in part at the 2001 Annual Meeting of the American Society of Human Genetics.