Race and breast cancer survival by intrinsic subtype based on PAM50 gene expression.
ABSTRACT 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: The lower breast cancer incidence in minority women and the higher breast cancer mortality in African American women than in white women are largely unexplained. The influence of breast cancer risk factors on these differences has received little attention. Racial/ethnic differences in breast cancer incidence and outcome were examined in 156,570 postmenopausal women participating in the Women's Health Initiative. Detailed information on breast cancer risk factors including mammography was collected, and participants were followed prospectively for breast cancer incidence, pathological breast cancer characteristics, and breast cancer mortality. Comparisons of breast cancer incidence and mortality across racial/ethnic groups were estimated as hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazard models. Tumor characteristics were compared as odds ratios (ORs) and 95% confidence intervals in logistic regression models. After median follow-up of 6.3 years, 3938 breast cancers were diagnosed. Age-adjusted incidences for all minority groups (i.e., African American, Hispanic, American Indian/Alaskan Native, and Asian/Pacific Islander) were lower than for white women, but adjustment for breast cancer risk factors accounted for the differences for all but African Americans (HR = 0.75, 95% CI = 0.61 to 0.92) corresponding to 29 cases and 44 cases per 10,000 person years for African American and white women, respectively. Breast cancers in African American women had unfavorable characteristics; 32% of those in African Americans but only 10% in whites were both high grade and estrogen receptor negative (adjusted OR = 4.70, 95% CI = 3.12 to 7.09). Moreover, after adjustment for prognostic factors, African American women had higher mortality after breast cancer than white women (HR = 1.79, 95% CI = 1.05 to 3.05) corresponding to nine and six deaths per 10 000 person-years from diagnosis in African American and white women, respectively. Differences in breast cancer incidence rates between most racial/ethnic groups were largely explained by risk factor distribution except in African Americans. However, breast cancers in African American women more commonly had characteristics of poor prognosis, which may contribute to their increased mortality after diagnosis.CancerSpectrum Knowledge Environment 04/2005; 97(6):439-48. DOI:10.1093/jnci/dji064
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ABSTRACT: The Life After Cancer Epidemiology (LACE) Study, a cohort of 2321 early stage breast cancer survivors, was established in 2000 to examine how modifiable behavioral risk factors affect quality of life and long-term survival. Women were recruited primarily from the Kaiser Permanente Northern California Cancer Registry (KPNCAL) and the Utah cancer registry (UCR), United States. Baseline data were collected, on average, at two years post-diagnosis through self-administered questionnaires that included information on demographics, medical history, anthropometry, diet, supplements, physical activity and quality of life. The purpose of this paper is to describe the creation and baseline characteristics of the cohort. Forty-six percent of women to whom questionnaires were mailed agreed to participate. The cohort which is 80% white, was diagnosed predominantly with Stage I and II breast cancer (93%), and will have been followed for 5.6 years post-diagnosis, on average, by the end of 2004. Women reported slightly over four daily servings of fruit and vegetables, well below the suggested 5-A-Day national guidelines. Compared to women free of cancer, physical activity patterns were similar, while weight gain, especially in younger women, was higher than is typical. These data suggest that in the early years post-diagnosis, breast cancer survivors exhibit similar patterns to the general population in many health behaviors.Cancer Causes and Control 07/2005; 16(5):545-56. DOI:10.1007/s10552-004-8340-3
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ABSTRACT: Reasons for the shorter survival of black breast cancer patients compared with their white counterparts are not completely understood. To evaluate the role of comorbidity in this racial disparity among breast cancer patients. Historical cohort from the Henry Ford Health System (a large comprehensive health system in Detroit, Mich) followed up for a median of 10 years. Patients (n = 906) included 264 black (29.1%) and 642 white (70.9%) women diagnosed as having breast cancer between 1985 and 1990. Detailed comorbidity data (268 comorbidities) and study data were abstracted from medical records and institutional, Surveillance, Epidemiology, and End Results, and Michigan State registries. Associations were analyzed with logistic and Cox regression. Breast cancer recurrence/progression and survival to death from all, breast cancer, and competing (non-breast cancer) causes. Of blacks, 64 (24.9%) died of breast cancer and 95 (37.0%) died of competing causes. Comparable data for whites were 115 (18.3%) and 202 (32.1%). Blacks had worse all-cause survival (hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.11-1.62), breast cancer-specific survival (HR, 1.47; 95% CI, 1.08-2.00), and competing-causes survival (HR, 1.27; 95% CI, 1.00-1.63). A total of 77 adverse comorbidities were associated with reduced survival. Adverse comorbidity count was associated with all-cause (adjusted HR, 1.29; 95% CI, 1.19-1.40) and competing-causes survival but was not associated with recurrence/progression or breast cancer-specific survival. At least 1 adverse comorbidity was observed in 221 (86.0%) blacks and 407 (65.7%) whites (odds ratio, 3.20; 95% CI, 2.17-4.72). Comparisons of unadjusted and comorbidity-adjusted HRs indicated that adverse comorbidity explained 49.1% of all-cause and 76.7% of competing-causes survival disparity. Diabetes and hypertension were particularly important in explaining disparity. More black breast cancer patients die of competing causes than of breast cancer. Effective control of comorbidity in black breast cancer patients should help improve life expectancy and lead to a reduction in survival disparities.JAMA The Journal of the American Medical Association 11/2005; 294(14):1765-72. DOI:10.1001/jama.294.14.1765