Traci N. Bethea

Parity, Lactation, and Breast Cancer Subtypes in African American Women: Results from the AMBER Consortium

BACKGROUND African American (AA) women have a disproportionately high incidence of estrogen receptor-negative (ER-) breast cancer, a subtype with a largely unexplained etiology. Because childbearing patterns also differ by race/ethnicity, with higher parity and a lower prevalence of lactation in AA women, we investigated the relation of parity and lactation to risk of specific breast cancer subtypes. METHODS Questionnaire data from two cohort and two case-control studies of breast cancer in AA women were combined and harmonized. Case patients were classified as ER+ (n = 2446), ER- (n = 1252), or triple negative (ER-, PR-, HER2-; n = 567) based on pathology data; there were 14180 control patients. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in polytomous logistic regression analysis with adjustment for study, age, reproductive and other risk factors. RESULTS ORs for parity relative to nulliparity was 0.92 (95% CI = 0.81 to 1.03) for ER+, 1.33 (95% CI = 1.11 to 1.59) for ER-, and 1.37 (95% CI = 1.06 to 1.70) for triple-negative breast cancer. Lactation was associated with a reduced risk of ER- (OR = 0.81, 95% CI = 0.69 to 0.95) but not ER+ cancer. ER- cancer risk increased with each additional birth in women who had not breastfed, with an OR of 1.68 (95% CI = 1.15 to 2.44) for 4 or more births relative to one birth with lactation. CONCLUSIONS The findings suggest that parous women who have not breastfed are at increased risk of ER- and triple-negative breast cancer. Promotion of lactation may be an effective tool for reducing occurrence of the subtypes that contribute disproportionately to breast cancer mortality.

Health Disparities and Cancer: Racial Disparities in Cancer Mortality in the United States, 2000–2010

Declining cancer incidence and mortality rates in the United States (U.S.) have continued through the first decade of the twenty-first century. Reductions in tobacco use, greater uptake of prevention measures, adoption of early detection methods, and improved treatments have resulted in improved outcomes for both men and women. However, Black Americans continue to have the higher cancer mortality rates and shorter survival times. This review discusses and compares the cancer mortality rates and mortality trends for Blacks and Whites. The complex relationship between socioeconomic status and race and its contribution to racial cancer disparities is discussed. Based on current trends and the potential and limitations of the patient protection and affordable care act with its mandate to reduce health care inequities, future trends, and challenges in cancer mortality disparities in the U.S. are explored.

Performance of three-biomarker immunohistochemistry for intrinsic breast cancer subtyping in the AMBER consortium

Background: Classification of breast cancer into intrinsic subtypes has clinical and epidemiologic importance. To examine accuracy of IHC-based methods for identifying intrinsic subtypes, a three-biomarker IHC panel was compared with the clinical record and RNA-based intrinsic (PAM50) subtypes. Methods: Automated scoring of estrogen receptor (ER), progesterone receptor (PR), and HER2 was performed on IHC-stained tissue microarrays comprising 1,920 cases from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Multiple cores (1–6/case) were collapsed to classify cases, and automated scoring was compared with the clinical record and to RNA-based subtyping. Results: Automated analysis of the three-biomarker IHC panel produced high agreement with the clinical record (93% for ER and HER2, and 88% for PR). Cases with low tumor cellularity and smaller core size had reduced agreement with the clinical record. IHC-based definitions had high agreement with the clinical record regardless of hormone receptor positivity threshold (1% vs. 10%), but a 10% threshold produced highest agreement with RNA-based intrinsic subtypes. Using a 10% threshold, IHC-based definitions identified the basal-like intrinsic subtype with high sensitivity (86%), although sensitivity was lower for luminal A, luminal B, and HER2-enriched subtypes (76%, 40%, and 37%, respectively). Conclusion: Three-biomarker IHC-based subtyping has reasonable accuracy for distinguishing basal-like from nonbasal-like, although additional biomarkers are required for accurate classification of luminal A, luminal B, and HER2-enriched cancers. Impact: Epidemiologic studies relying on three-biomarker IHC status for subtype classification should use caution when distinguishing luminal A from luminal B and when interpreting findings for HER2-enriched cancers. Cancer Epidemiol Biomarkers Prev; 25(3); 470–8. ©2015 AACR.

Important Role of Menarche in Development of Estrogen Receptor–Negative Breast Cancer in African American Women

BACKGROUND Menarche is a critical time point for diverging fates of mammary cells of origin. African American women have young age at menarche, which could be associated with their high rates of estrogen receptor-negative (ER-) breast cancer. METHODS In the AMBER Consortium, using harmonized data from 4426 African American women with breast cancer and 17 474 controls, we used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for ages at menarche and first live birth (FLB), and the interval between, in relation to ER+ and ER- breast cancer. All statistical tests were two-sided. RESULTS Risk of ER- breast cancer was reduced with later age at menarche among both parous and nulliparous women (≥15 vs <11 years OR = 0.62, 95% CI = 0.48 to 0.81 and OR = 0.56, 95% CI = 0.29 to 1.10, respectively), with no effect of age at FLB. For ER+ breast cancer, the inverse association was weaker among nulliparous women. While longer intervals between menarche and FLB were associated with increased risk of ER+ breast cancer in a dose-response fashion (OR for 20 year interval = 1.39, 95% CI = 1.08 to 1.79, P trend = .003), ER- risk was only increased for intervals up to 14 years and not beyond (P trend = .33). CONCLUSIONS While ER- breast cancer risk was markedly reduced in women with a late age at menarche, there was not a clear pattern of increased risk with longer interval between menarche and FLB, as was observed for ER+ breast cancer. These findings indicate that etiologic pathways involving adolescence and pregnancy may differ for ER- and ER+ breast cancer.

A Pooled Analysis of Body Mass Index and Mortality among African Americans

Pooled analyses among whites and East Asians have demonstrated positive associations between all-cause mortality and body mass index (BMI), but studies of African Americans have yielded less consistent results. We examined the association between BMI and all-cause mortality in a sample of African Americans pooled from seven prospective cohort studies: NIH-AARP, 1995–2009; Adventist Health Study 2, 2002–2008; Black Womens Health Study, 1995–2009; Cancer Prevention Study II, 1982–2008; Multiethnic Cohort Study, 1993–2007; Prostate, Lung, Colorectal and Ovarian Screening Trial, 1993–2009; Southern Community Cohort Study, 2002–2009. 239,526 African Americans (including 100,175 never smokers without baseline heart disease, stroke, or cancer), age 30–104 (mean 52) and 71% female, were followed up to 26.5 years (mean 11.7). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality were derived from multivariate Cox proportional hazards models. Among healthy, never smokers (11,386 deaths), HRs (CI) for BMI 25–27.4, 27.5–29.9, 30–34.9, 35–39.9, 40–49.9, and 50–60 kg/m2 were 1.02 (0.92–1.12), 1.06 (0.95–1.18), 1.32 (1.18–1.47), 1.54 (1.29–1.83), 1.93 (1.46–2.56), and 1.93 (0.80–4.69), respectively among men and 1.06 (0.99–1.15), 1.15 (1.06–1.25), 1.24 (1.15–1.34), 1.58 (1.43–1.74), 1.80 (1.60–2.02), and 2.31 (1.74–3.07) respectively among women (reference category 22.5–24.9). HRs were highest among those with the highest educational attainment, longest follow-up, and for cardiovascular disease mortality. Obesity was associated with a higher risk of mortality in African Americans, similar to that observed in pooled analyses of whites and East Asians. This study provides compelling evidence to support public health efforts to prevent excess weight gain and obesity in African Americans.

The relationship between rural status, individual characteristics, and self-rated health in the Behavioral Risk Factor Surveillance System.

PURPOSE To examine rural status and social factors as predictors of self-rated health in community-dwelling adults in the United States. METHODS This study uses multinomial logistic and cumulative logistic models to evaluate the associations of interest in the 2006 U.S. Behavioral Risk Factor Surveillance System, a cross-sectional survey of 347,709 noninstitutionalized adults. FINDINGS Self-rated health was poorer among rural residents, compared to urban residents (OR = 1.77, 95% CI: 1.54, 1.90). However, underlying risk factors such as obesity, low income, and low educational attainment were found to vary by rural status and account for the observed increased risk (OR = 1.03, 95% CI: 0.94, 1.12). There was little evidence of effect modification by rural status, though the association between obesity and self-rated health was stronger among urban residents (OR = 2.50, 95% CI: 2.38, 2.64) than among rural residents (OR = 2.18, 95% CI: 2.03, 2.34). CONCLUSIONS Our findings suggest that differences in self-rated health by rural status were attributable to differential distributions of participant characteristics and not due to differential effects of those characteristics.

A Prospective Study of Physical Activity and Breast Cancer Incidence in African-American Women

Background: Physical activity has been associated with reduced risk of breast cancer. Evidence on the association in African Americans is limited. Methods: With prospective data from the Black Womens Health Study, we assessed vigorous exercise and walking in relation to incidence of invasive breast cancer overall (n = 1,364), estrogen receptor–positive (ER+, n = 688) cancer, and estrogen receptor–negative (ER−, n = 405) cancer, based on 307,672 person-years of follow-up of 44,708 African-American women ages 30 years or older at enrollment. Cox proportional hazards models estimated incidence rate ratios (IRR) and 95% confidence intervals (CI). Results: Vigorous exercise at baseline was inversely associated with overall breast cancer incidence (Ptrend = 0.05): the IRR for ≥7 h/wk relative to <1 h/wk was 0.74 (95% CI, 0.57–0.96). The association did not differ by ER status. Brisk walking for ≥7 h/wk was associated with a reduction similar to that for vigorous exercise. Vigorous exercise at the age of 30 years, 21 years, or in high school was not associated with breast cancer incidence. Sitting for long periods at work or watching TV was not significantly associated with breast cancer incidence. Conclusion: High levels of vigorous exercise or brisk walking may be associated with a reduction in incidence of breast cancer in African-American women. Impact: These results provide informative data on a potential modifiable risk factor, exercise, for breast cancer in African-American women. Cancer Epidemiol Biomarkers Prev; 23(11); 2522–31. ©2014 AACR.

A pooled analysis of body mass index and pancreatic cancer mortality in African Americans

Background: Pancreatic cancer is a leading cause of cancer-related mortality in the United States and both incidence and mortality are highest in African Americans. Obesity is also disproportionately high in African Americans, but limited data are available on the relation of obesity to pancreatic cancer in this population. Methods: Seven large prospective cohort studies pooled data from African American participants. Body mass index (BMI) was calculated from self-reported height and weight at baseline. Cox regression was used to calculate HRs and 95% confidence intervals (CI) for levels of BMI relative to BMI 18.5–24.9, with adjustment for covariates. Primary analyses were restricted to participants with ≥5 years of follow-up because weight loss before diagnosis may have influenced baseline BMI in cases who died during early follow-up. Results: In follow-up of 239,597 participants, 897 pancreatic cancer deaths occurred. HRs were 1.08 (95% CI, 0.90–1.31) for BMI 25.0 to 29.9, 1.25 (95% CI, 0.99–1.57) for BMI 30.0 to 34.9, and 1.31 (95% CI, 0.97–1.77) for BMI ≥35.0 among those with ≥5 years of follow-up (Ptrend = 0.03). The association was evident among both sexes and was independent of a history of diabetes. A stronger association was observed among never-smokers (BMI ≥30 vs. referent: HR = 1.44; 95% CI, 1.02–2.03) than among smokers (HR = 1.16; 95% CI, 0.87–1.54; Pinteraction = 0.02). Conclusion: The findings suggest that obesity is independently associated with increased pancreatic cancer mortality in African Americans. Impact: Interventions to reduce obesity may also reduce risk of pancreatic cancer mortality, particularly among never-smokers. Cancer Epidemiol Biomarkers Prev; 23(10); 2119–25. ©2014 AACR.

Long-Term Exposure to NO2 and Ozone and Hypertension Incidence in the Black Women’s Health Study

BACKGROUND Evidence shows that exposure to air pollutants can increase blood pressure in the short and long term. Some studies show higher levels of hypertension prevalence in areas of high pollution. Few data exist on the association of air pollution with hypertension incidence. The purpose of the present study was to prospectively assess the associations of the traffic‐related nitrogen dioxide (NO2) and of ozone with the incidence of hypertension in the Black Womens Health Study (BWHS), a large cohort study of African American women. METHODS We used Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for hypertension associated with exposure to NO2 and ozone among 33,771 BWHS participants. NO2 and ozone levels at participant residential locations were estimated with validated models. RESULTS From 1995 to 2011, 9,570 incident cases of hypertension occurred in a total of 348,154 person‐years (median follow‐up time, 11 years). The multivariable HRs per interquartile range of NO2 (9.7 ppb) and ozone (6.7 ppb) were 0.92 (95% CI = 0.86, 0.98) and 1.09 (95% CI = 1.00, 1.18). CONCLUSIONS In this large cohort of African American women, higher ozone levels were associated with an increase in hypertension incidence. Higher NO2 levels were not associated with greater hypertension incidence; indeed, incidence was lower at higher NO2 levels.

Confronting racism and sexism to improve men's health.

Two fundamental determinants of men’s health are confronted—racism and sexism—that the authors believe underlie many of the health disparities documented between women and men and place men of color at particular disadvantage in U.S. society. In doing so, the authors contend that race and gender, as well as racism and sexism, are social constructs and, therefore, amenable to change. They hope to allay concerns that gains in the health of men will come at the expense of continued advances in the health of women. Instead, by better understanding how the harsh intersections of racism and sexism have contorted roles for men of color and damaged their social ties, a healing process in intimate relationships, extended families, and entire communities may be fostered. Only by reforming historical injustices and reuniting men with their partners, families, and communities will sustained improvements in their health and well-being be realized.