BRCA1 and BRCA2 mutations account for a large proportion of ovarian carcinoma cases

Abstract

BACKGROUND It is believed that BRCA1 and BRCA2 germline mutations account for the majority of hereditary ovarian carcinomas; however, to the authors' knowledge, there are scant data on the prevalence and spectrum of mutations, genotype/phenotype correlations, tumor histology, and family history characteristics. To address this gap, the authors conducted a population‐based study of 232 incident epithelial ovarian carcinomas in the Tampa Bay area. METHODS Genetic testing for the BRCA1 and BRCA2 genes was performed through full sequencing and BRCA1 rearrangement testing. RESULTS Of 209 women with invasive ovarian carcinoma, 32 women (15.3%) had mutations in BRCA1 or BRCA2, including 20 BRCA1 mutations and 12 BRCA2 mutations. Of the BRCA2 mutations, 58% were outside the “ovarian cancer cluster region” (OCCR). Variants of uncertain significance were detected in 8.2% of women with invasive ovarian carcinoma. No mutations were identified in women with borderline or invasive mucinous tumors. Among the BRCA mutation‐positive women, 63% had serous tumors. A family history of breast and/or ovarian carcinoma was reported in 65%, 75%, and 43.5% of relatives of BRCA1 carriers, BRCA2 carriers, and non‐BRCA1/BRCA2 carriers, respectively. CONCLUSIONS The data from this study suggested that 1) previous studies may have underestimated the frequency of BRCA1 and BRCA2 mutations in ovarian carcinomas, especially outside the OCCR; 2) it may be reasonable to offer genetic counseling to any woman with an invasive, nonmucinous epithelial ovarian tumor; and 3) among patients with invasive ovarian carcinoma, family history is not sufficiently accurate to predict mutation status. Cancer 2005. © 2005 American Cancer Society.

Improved survival in BRCA2 carriers with ovarian cancer

“…As described previously [3], of the 232 TBOCS cases, 209 were diagnosed with invasive cancer and 23 were diagnosed with borderline tumors. The average age at diagnosis was 53 years among BRCA1 carriers (n = 20 women), 58 years among BRCA2 carriers (n = 12 women), and 57 years among women with invasive sporadic tumors (n = 177).…”

“…Further details about study design, population, and data collection methods have been published previously [3]. Briefly, study participants were from a heavily populated two-county region of west central Florida, with a population in excess of two million.…”

“…Approximately 5-14% of invasive ovarian cancers are believed to be due to hereditary susceptibility [1][2][3], of which mutations in the BRCA1 and BRCA2 genes account for the majority [4,5]. The lifetime risk of developing ovarian cancer in BRCA1 and BRCA2 carriers is 28-44% [1,2,6,7].…”

“…The lifetime risk of developing ovarian cancer in BRCA1 and BRCA2 carriers is 28-44% [1,2,6,7]. Estimates of the frequency of BRCA1 and BRCA2 germline mutations in ovarian cancer patients have ranged between 2-12% and 2-6% for BRCA1 and BRCA2 mutations, respectively [2,3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22].…”

Impact of a Randomized Controlled Educational Trial to Improve Physician Practice Behaviors Around Screening for Inherited Breast Cancer

“…Those with BRCA mutations account for 7 % of all breast cancers and 10 % to 15 % of ovarian cancers. 2,3 The discovery of links between BRCA mutations and breast cancer creates an opportunity to identify individuals at risk and to intervene early in the disease process. 4 Knowing how to screen appropriately for genetic risk factors for breast cancer and when to offer genetic testing are core skills for primary care physicians (PCPs), especially given the relative scarcity of genetic counselors.…”