Intrinsic subtypes from PAM50 gene expression assay in a population-based breast cancer cohort: Differences by age, race, and tumor characteristics

Background: Data are lacking to describe gene expression-based breast cancer intrinsic subtype patterns for population-based patient groups. Methods:Westudied a diverse cohort ofwomenwith breast cancer from the Life After Cancer Epidemiology and Pathways studies. RNA was extracted from 1mmpunches from fixed tumor tissue. Quantitative reversetranscriptase PCR was conducted for the 50 genes that comprise the PAM50 intrinsic subtype classifier. Results: In a subcohort of 1,319 women, the overall subtype distribution based onPAM50 was 53.1% luminal A, 20.5% luminal B, 13.0% HER2-enriched, 9.8% basal-like, and 3.6% normal-like. Among low-risk endocrinepositive tumors (i.e., estrogen and progesterone receptor positive by immunohistochemistry, HER2 negative, and low histologic grade), only 76.5% were categorized as luminal A by PAM50. Continuous-scale luminal A, luminal B, HER2-enriched, and normal-like scores fromPAM50were mutually positively correlated. Basal-like score was inversely correlated with other subtypes. The proportion with non-luminal A subtype decreased with older age at diagnosis, PTrend < 0.0001. Compared with non-Hispanic Whites, African American women were more likely to have basal-like tumors, age-adjusted OR = 4.4 [95% confidence intervals (CI), 2.3-8.4], whereas Asian and Pacific Islander women had reduced odds of basal-like subtype, OR=0.5 (95% CI, 0.3-0.9). Conclusions: Our data indicate that over 50% of breast cancers treated in the community have luminal A subtype. Gene expression-based classification shifted some tumors categorized as low risk by surrogate clinicopathologic criteria to higher-risk subtypes. Impact: Subtyping in a population-based cohort revealed distinct profiles by age and race.