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Engel, Christoph; Rhiem, Kerstin; Hahnen, Eric; Loibl, Sibylle; Weber, Karsten E.; Seiler, Sabine; Zachariae, Silke; Hauke, Jan; Wappenschmidt, Barbara; Waha, Anke; Blümcke, Britta; Kiechle, Marion; Meindl, Alfons; Niederacher, Dieter; Bartram, Claus R.; Speiser, Dorothee; Schlegelberger, Brigitte; Arnold, Norbert; Wieacker, Peter; Leinert, Elena; Gehrig, Andrea; Briest, Susanne; Kast, Karin; Riess, Olaf; Emons, Günter; Weber, Bernhard H. F.; Engel, Jutta; Schmutzler, Rita K. (2018): Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history. In: BMC Cancer 18:265
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Abstract

BACKGROUND There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group. METHODS The study comprised 802 women (median age 40~years, range 19-76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation. RESULTS A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20-29~years compared to 6.9% in the age group 60-69~years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10~year decrease, 95%CI 1.50-2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50~years. CONCLUSIONS Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50~years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.