Abstract P3-07-01: Family history of breast cancer in a population-based breast cancer cohort: No association with PAM50 intrinsic subtype or prognosis

Basal-like intrinsic subtype and poor prognosis are characteristic of breast cancers in BRCA1 families, but other genes also confer inherited predisposition to breast cancer, and subtype associations may differ. The objective of this study was to examine whether family history of breast cancer is associated with basal-like subtype and/or poor prognosis in a population-based sample of women with breast cancer. METHODS: The study population was the Life After Cancer Epidemiology (LACE) cohort, diagnosed with breast cancer in 1996-2000, and the Pathways cohort, diagnosed with breast cancer in 2006-2008. History of breast cancer among first-degree relatives was obtained by self-report at study enrollment, and women were followed for breast cancer recurrence and mortality. Primary breast cancer tissue was obtained for a case-cohort sample. Intrinsic subtypes were classified based on RT-PCR assay of 50 genes (PAM50). Sample-weighted subtype distributions were compared by family history. Hazard ratios (HR) for recurrence and mortality were estimated from Cox proportional hazards models. RESULTS: From 4,256 women in the parent cohorts who responded to the family history question, 20.5% reported a first-degree family history of breast cancer. Among women with family history, 80.6% were diagnosed at ages 50 and older, compared with 76.3% of women without family history, p = 0.007. Among cases with family history, 79.2% were non-Hispanic whites, compared with 72.3% of cases without family history, p < 0.001. Within the subcohort with PAM50 results (n = 1,319), cases with and without family history had 8.5% and 10.2% prevalence of basal-like tumors, respectively, p = 0.27. For cases diagnosed before age 50, the prevalences of basal-like subtype for women with and without family history were 18.6% and 15.9%, respectively, p = 0.62. Women with family history had similar recurrence risk to those without, HR 0.82 (95% CI 0.61, 1.11; age- and race-adjusted). Women with family history had a suggestive reduced risk of death from all causes, HR 0.75 (95% 0.55, 1.02). Family history was not significantly associated with recurrence or survival within any intrinsic subtype group. DISCUSSION: Although BRCA1 is known to predispose to basal-like subtype, we found no association between family history of breast cancer and basal-like subtype or worse prognosis in this population-based cohort. Mutation status for BRCA1 and other cancer susceptibility genes are unknown for cohort members. First-degree family history of breast cancer may represent the presence of one of the several inherited breast cancer susceptibility genes, or chance aggregation of sporadic cases. Particularly for a woman diagnosed at an older age, her mother and sisters would also have reached ages when sporadic breast cancer incidence is high. Among women diagnosed before age 50, family history was associated with a small and non-significant excess of basal-like tumors. Implications of this study are that for women from the general population diagnosed with breast cancer, a first-degree family history of breast cancer indicates neither a higher probability of a basal-like tumor nor worse prognosis. Support: NIH CA129059 and CA105274. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-01.