Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression

Breast Cancer Research and Treatment (Impact Factor: 3.94). 03/2014; 144(3). DOI: 10.1007/s10549-014-2899-5
Source: PubMed


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.

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    ABSTRACT: Breast cancer accounts for over 200,000 annual cases among women in the United States, and is the second leading cause of cancer-related deaths. However, few studies have investigated the association between breast cancer subtype and survival among African-American women. We analyzed cancer-related deaths among African-American women using data obtained from the SEER database linked to the 2000 U.S. census data. We examined distribution of baseline socio-demographic and clinical characteristics by breast cancer subtypes and used Cox proportional hazard models to determine associations between breast cancer subtypes and cancer-related mortality, adjusting for age, socio-economic status, stage at diagnosis, and treatment. Among 19,836 female breast cancer cases, 54.4 % were diagnosed with the HER2-/HR+ subtype, with the majority of those cases occurring among women ages 55 and older. However, after adjusting for age, stage, and treatment type (surgery, radiation, or no radiation and/or cancer-directed surgery), TNBC (HR 2.34; 95 % CI 1.95-2.81) and HER2+/HR- (HR 1.39, 95 % CI 1.08-1.79) cases had significantly higher hazards of cancer-related deaths compared with HER2+/HR+ cases. Adjusting for socio-economic status did not significantly alter these associations. African-American women with TNBC were more likely to have a cancer-related death than African-American women with other breast cancer subtypes. This association remained after adjustments for age, stage, treatment, and socio-economic status. Further studies are needed to identify subtype-specific risk and prognostic factors aimed at better informing prevention efforts for all women.
    Breast Cancer Research and Treatment 08/2015; 153(1). DOI:10.1007/s10549-015-3528-7 · 3.94 Impact Factor
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    ABSTRACT: Purpose: This study examines the factors distinguishing breast cancer (BC) subtypes. Methods: We examined subtypes in 629 women with invasive BC, diagnosed from 2006 to 2012, and enrolled in an epidemiological study in New Jersey. Using molecular characteristics from pathology reports, BCs were categorized as luminal A, luminal B, non-luminal HER2-expressing, or triple-negative breast cancer (TNBC) subtypes. Multinomial logistic models (luminal A as referent) were used to describe BC subtype associations. Results: Women with luminal B tumors were more likely to be younger at diagnosis [odds ratio (OR) 1.8, 95 % confidence interval (CI) 1.0-3.4] and to have higher-grade (OR 2.6, 95 % CI 1.5-4.7), larger (OR 1.9, 95 % CI 1.0-3.6), and Ki67-positive tumors (OR 2.1, 95 % CI 1.1-4.0). Women with non-luminal HER2-expressing BCs were more likely to have higher-grade tumors (OR 14.5, 95 % CI 5.3-39.7). Women with TNBCs were more likely to be African-American (OR 1.9, 95 % CI 1.0-3.4) and to have higher-grade (OR 9.7, 95 % CI 5.1-18.4), larger (OR 2.2, 95 % CI 1.0-4.8), and Ki67-positive (OR 2.9, 95 % CI 1.6-5.2) tumors. Notably, compared to the luminal A subtype, luminal B, non-luminal HER2-expressing, and triple-negative subtypes were more frequently self-detected; however, these associations were attenuated in multivariable models. Conclusions: These findings suggest that some BC subtypes were associated with features denoting more aggressive phenotypes, namely higher grade, larger size, and Ki67 positivity, and possibly patient self-detection among some women. These findings highlight a need for enhanced screening, particularly among younger women, racial/ethnic minorities, and lower socioeconomic subgroups.
    Cancer Causes and Control 09/2015; 26(12). DOI:10.1007/s10552-015-0667-4 · 2.74 Impact Factor

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