Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression
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To evaluate whether differences in PAM50 breast cancer (BC) intrinsic (Luminal A, Luminal B, Basal-like, and HER2-enriched) subtypes help explain the Black–White BC survival disparity. Utilizing a stratified case-cohort design, this study included 1,635 women from the Pathways and Life After Cancer Epidemiology cohorts, selecting women with tumors based upon IHC classification, recurrences, and deaths.One millimeter punches were obtained from tumor tissue, and expression of the PAM50 genes for molecular subtype was determined by RT-qPCR of extracted RNA. Cox proportional hazards models were used to analyze associations between race and BC outcomes, adjusted for PAM50 BC subtype. All tests of statistical significance were two-sided. Black women had a higher prevalence of the Basal-like BC subtype. Adjusted for potential confounding variables and disease characteristics at diagnosis, Black women had higher risks of recurrence (HR 1.65, 95 % CI 1.06–2.57) and breast cancer-specific mortality (HR 1.71, 95 % CI 1.02–2.86) than White women, but adjusting further for subtype did not attenuate survival disparities. By contrast, Hispanic women had a lower risk of recurrence (HR 0.54, 95 % CI 0.30–0.96) than Whites. Among those with the Basal-like subtype, Black women had a similar recurrence risk as women in other race groups but a higher recurrence risk for all other subtypes. Hispanic women had a lower recurrence risk within each subtype, though associations were not significant, given limited power. Although Black women had a higher risk of the Basal-like subtype, which has poor prognosis, this did not explain the Black–White BC survival disparity.
KeywordsRace Ethnicity Breast cancer survival Breast cancer mortality Gene expression Molecular subtype Intrinsic subtype PAM50
This work was supported by the National Institutes of Health (R01 CA129059 and R01 CA105274). The Utah Cancer Registry is funded by Contract No. HHSN261201000026C from the National Cancer Institute Surveillance Epidemiology and End Results (SEER) program and additional support from the Utah State Department of Health and the University of Utah. PSB has an interest in Bioclassifier LLC and University Genomics.
Conflict of interest
The other authors declare they have no competing interests.
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