Founder BRCA1 and BRCA2 mutations in early-onset French Canadian breast cancer cases unselected for family history

Recently, founder BRCA1 and BRCA2 mutations were identified in Canadian bre ast cancer and breast-ovarian cancer families of French ancestry. The prese nce of a breast cancer case diagnosed at younger than 36 years of age was s trongly predictive of the presence of any founder mutation screened. Here w e report the occurrence of founder BRCA1 and BRCA2 mutations in a series of 61 French Canadian women with invasive breast cancer diagnosed at age 40 o r younger, unselected for family history of breast and ovarian cancer. Germ line mutations in BRCA1 (n = 4) and BRCA2 (n = 4) were identified in 8 of 6 1 (13%) cases. All BRCA1 mutations were found in invasive ductal carcinomas , the most common histologic type of tumor in this series. In contrast, the BRCA2 mutations were found in tumors of various histologic types: two duct al carcinomas, a tumor containing both ductal and lobular histologic types and an invasive lobular carcinoma. Of the 37 women with at least one first- , second- or third-degree relative with breast or ovarian cancer and the 24 women with no history of these cancers, 7 (19%) and 1 (4%), respectively, were mutation carriers. The seven mutation carriers with a family history o f cancer had at least one first-, second- or third-degree relative with a b reast cancer diagnosis at less than 51 years of age. The identification of founder BRCA1 and BRCA2 mutations in young-onset breast cancer cases unsele cted for family history can facilitate carrier detection when the expected yield of a comprehensive screen may be low. (C) 2001 Wiley-Liss, Inc.