Genetic, clinic and histopathologic characterization of BRCA-associated hereditary breast and ovarian cancer in southwestern Finland

Abstract

<p>We have analyzed the histopathological, clinical, and genetic characteristics in hereditary breast and ovarian cancer patients of counselled families from 1996 up to today in the southwestern Finland population. In this study we analyzed the incidence of different <i>BRCA1 </i>and <i>BRCA2 </i>pathogenic variants (PV). 1211 families were evaluated, and the families were classified as 38 <i>BRCA1 </i>families, 48 <i>BRCA2</i> families, 689 non-<i>BRCA </i>families and 436 other counselled families (criteria for genetic testing was not met). In those families, the study consisted of 44 <i>BRCA1 </i>breast and/or ovarian cancer patients, 58 <i>BRCA2</i> cancer patients, 602 non-<i>BRCA </i>patients and 328 other counselled patients. Breast cancer mean onset was 4.6 years earlier in <i>BRCA1 </i>carriers compared to <i>BRCA2 </i>(p = 0.07, a trend) and ovarian cancer onset almost 11 years earlier in <i>BRCA1 </i>families (p < 0.05). In <i>BRCA </i>families the onset of ovarian cancer was later than 40 years, and <i>BRCA2</i>-origin breast cancer was seen as late as 78 years. The <i>BRCA </i>PV (9%) increases the risk for same patient having both ovarian and breast cancer with a twofold risk when compared to non-<i>BRCA </i>group (4%) (95% CI p < 0.05). Triple-negativity in <i>BRCA1 </i>(42%) carriers is approximately 2.6 times vs more common than in <i>BRCA2 </i>carriers (16%) (p < 0.05). The risk ratio for bilateral breast cancer is approximately four times when compared <i>BRCA2 </i>(17%) and other counselled patients' group (4%) (p < 0.05). 27% southwestern <i>BRCA2</i>-families have a unique PV, and correspondingly 39% of <i>BRCA1</i>-families. The results of this analysis allow improved prediction of cancer risk in high-risk hereditary breast and ovarian families in southwestern Finland and improve long term follow-up programs. According to the result it could be justified to have the discussion about prophylactic salpingo-oophorectomy by the age of 40 years. The possibility of late breast cancer onset in <i>BRCA2 </i>carriers supports the lifelong follow-up in <i>BRCA </i>carriers. Cancer onset is similar between <i>BRCA2 </i>carries and non-BRCA high-risk families. This study evaluated mutation profile of <i>BRCA </i>in southwestern Finland. In this study genotype-phenotype correlation was not found<br></p>