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Breast cancer mortality is higher in Black women than in White women. The prevalence of type 2 diabetes mellitus is also higher, yet data on whether diabetes affects breast cancer mortality in this population are lacking. We investigated the relation of diabetes at the time of breast cancer diagnosis to breast cancer mortality in the Black Women's Health Study, a prospective cohort study.1,621 Black women with invasive breast cancer diagnosed in 1995-2013 were followed by mailed questionnaires and searches of the National Death Index. Multivariable Cox regression analysis was used to compute hazard ratios (HRs) for diabetes in relation to breast cancer mortality and all-cause mortality, with adjustment for age, stage, treatment modality, estrogen receptor (ER) status, and body mass index.There were 368 deaths during follow-up, of which 273 were due to breast cancer. Breast cancer mortality was significantly increased in women who had been diagnosed with diabetes at least 5 years before breast cancer occurrence, HR 1.86 (95% CI 1.20-2.89), with elevations observed for both ER+ and ER- breast cancer. All-cause mortality was also higher in diabetics, with HRs of 1.54 (95% CI 1.12-2.07) overall and 2.26 (95% CI 1.62-3.15) for ≥5-year duration of diabetes relative to non-diabetics.Our results present the first solid evidence of a positive association of type 2 diabetes with breast cancer mortality in Black women. Given the higher prevalence and earlier onset of type 2 diabetes in Black women, it is likely that diabetes contributes to racial disparities in breast cancer mortality.

Purpose Breast cancer risk prediction models have underestimated risk for African American women, contributing to lower recruitment rates in prevention trials. A model previously developed for African American women was found to underestimate risk in the Black Women's Health Study (BWHS). Methods We developed a breast cancer risk model for African American women using relative risks derived from 10 years of follow-up of BWHS participants age 30 to 69 years at baseline. Using the subsequent 5 years of follow-up data, we evaluated calibration as the ratio of expected to observed number of breast cancers and assessed discriminatory accuracy using the concordance statistic. Results The BWHS model included family history, previous biopsy, body mass index at age 18 years, age at menarche, age at first birth, oral contraceptive use, bilateral oophorectomy, estrogen plus progestin use, and height. There was good agreement between predicted and observed number of breast cancers overall (expected-to-observed ratio, 0.96; 95% CI, 0.88 to 1.05) and in most risk factor categories. Discriminatory accuracy was higher for women younger than age 50 years (area under the curve [AUC], 0.62; 95% CI, 0.58 to 0.65) than for women age ≥ 50 years (AUC, 0.56; 95% CI, 0.53 to 0.59). Using a 5-year predicted risk of 1.66% or greater as a cut point, 2.8% of women younger than 50 years old and 32.2% of women ≥ 50 years old were classified as being at elevated risk of invasive breast cancer. Conclusion The BWHS model was well calibrated overall, and the predictive ability was best for younger women. The proportion of women predicted to meet the 1.66% cut point commonly used to determine eligibility for breast cancer prevention trials was greatly increased relative to previous models.

Background: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. Methods: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799 500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). Results: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22–5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82–1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. Conclusions: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

A growing body of evidence suggests that pregnancy complications may signal future chronic disease risk in mothers.1-5 For example, it is well-known that gestational diabetes is a precursor of type 2 diabetes6-7; 50%-70% of women experiencing this pregnancy complication go on to develop type 2 diabetes.8 Interventions after a pregnancy complicated by gestational diabetes (such as weight reduction) have led to a substantial decrease in future development of type 2 diabetes.6, 9-12 Thus, evaluation of the association between other common pregnancy complications and type 2 diabetes risk is warranted, especially among black women, as they have one of the highest rates of type 2 diabetes in the U.S.13 A pregnancy complication that is of particular concern for black women is preterm birth, which affects up to 17% of pregnancies in this racial group.14-16 In fact, black women are almost twice as likely to experience a preterm birth compared with white women.17 Preterm birth and type 2 diabetes share several underlying risk factors, including higher levels of certain inflammatory markers, such as tumor necrosis factor α and interleukin-1β.16-18 These shared factors suggest that preterm birth may be a signal for elevated inflammatory markers and possibly future development of type 2 diabetes in some women. Given that black women have a higher prevalence of both preterm birth and type 2 diabetes,14-17 we evaluated the association between this pregnancy complication and type 2 diabetes in black mothers. This study was conducted in a large cohort of black women participating in the Black Women's Health Study. We accounted for a number of potential confounders, including maternal age, education, and body size. While the association of preterm birth with type 2 diabetes has been explored in predominantly white populations,3-4 to our knowledge, it has not been evaluated in black women. If an appreciable association is found, targeted interventions among black women experiencing a preterm birth could lead to a decrease in risk of type 2 diabetes.

African American women are more likely to undergo hysterectomy, with or without bilateral oophorectomy, at younger ages than white women. It is well established that women who have a bilateral oophorectomy at younger ages are at reduced risk of breast cancer, and there is some evidence of an increased risk of colorectal and lung cancer. Using data from 44,514 women in the Black Women’s Health Study, we prospectively investigated the relation of hysterectomy and oophorectomy to incidence of breast, colorectal, and lung cancer and to mortality from cancer. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazards regression with control for confounding factors. During 16 years of follow-up, hysterectomy alone, relative to no hysterectomy, was not associated with risk of breast, lung, or colorectal cancer. Bilateral oophorectomy, relative to hysterectomy with ovarian conservation, was inversely associated with risk of estrogen receptor-positive (ER+) breast cancer (HR 0.62; 95 % CI 0.45–0.85) but not with ER-negative breast cancer; age at surgery and menopausal hormone use did not modify the associations. HRs for the association of bilateral oophorectomy with incidence of colorectal and lung cancer were nonsignificantly increased for women who had surgery before age 40 years and had used menopausal hormones for less than 2 years (HR 1.65; 95 % CI 0.73–3.73 for colorectal cancer and HR 1.71; 95 % CI 0.68–4.31 for lung cancer). Bilateral oophorectomy was not associated with cancer mortality. Bilateral oophorectomy was associated with reduced risk of ER+ breast cancer regardless of age at surgery and use of menopausal hormones. There were nonsignificant increases in risk of colorectal and lung cancer for women with oophorectomy at younger ages and short duration of menopausal hormone use.

Active smoking and passive smoking have been associated with increased risk of breast cancer. The purpose of the present study was to prospectively assess associations of smoking with breast cancer and identify subgroups at higher risk among African-American women. Based on 1,377 incident cases identified during 14 years of follow-up in the Black Women’s Health Study, we assessed active and passive smoking in relation to breast cancer incidence by menopausal status, estrogen receptor status, and other factors. Incidence rate ratios (IRR) and 95 % confidence intervals (CI) for categories of smoking relative to no active or passive smoking were calculated from Cox proportional hazards models, controlling for breast cancer risk factors. Active smoking was associated with increased risk of premenopausal breast cancer. The IRR was 1.21 (95 % CI 0.90–1.62) for premenopausal breast cancer overall and 1.70 (95 % CI 1.05–2.75) for premenopausal breast cancer associated with beginning smoking before age 18 together with accumulation of ≥20 pack years. The positive association with premenopausal breast cancer was most apparent for estrogen-receptor-positive cancer. Passive smoking was also associated with increased risk of premenopausal breast cancer (IRR = 1.42, 95 % CI 1.09–1.85), based on information on passive smoking at home and work. Neither active nor passive smoking was associated with increased risk of postmenopausal breast cancer. These results strengthen the evidence that both active and passive smoking increase the incidence of premenopausal breast cancer.

Estrogen receptor-negative (ER(-)) breast cancer has few known or modifiable risk factors. Because ER(-) tumors account for only 15% to 20% of breast cancers, large pooled analyses are necessary to evaluate precisely the suspected inverse association between fruit and vegetable intake and risk of ER(-) breast cancer.Among 993 466 women followed for 11 to 20 years in 20 cohort studies, we documented 19 869 estrogen receptor positive (ER(+)) and 4821 ER(-) breast cancers. We calculated study-specific multivariable relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression analyses and then combined them using a random-effects model. All statistical tests were two-sided.Total fruit and vegetable intake was statistically significantly inversely associated with risk of ER(-) breast cancer but not with risk of breast cancer overall or of ER(+) tumors. The inverse association for ER(-) tumors was observed primarily for vegetable consumption. The pooled relative risks comparing the highest vs lowest quintile of total vegetable consumption were 0.82 (95% CI = 0.74 to 0.90) for ER(-) breast cancer and 1.04 (95% CI = 0.97 to 1.11) for ER(+) breast cancer (P (common-effects) by ER status.001). Total fruit consumption was non-statistically significantly associated with risk of ER(-) breast cancer (pooled multivariable RR comparing the highest vs lowest quintile = 0.94, 95% CI = 0.85 to 1.04).We observed no association between total fruit and vegetable intake and risk of overall breast cancer. However, vegetable consumption was inversely associated with risk of ER(-) breast cancer in our large pooled analyses.

Socioeconomic status (SES) for both individuals and neighborhoods has been positively associated with incidence of breast cancer, although not consistently. The authors conducted an assessment of these factors among African-American women, based on data from the Black Women's Health Study, a prospective cohort study of 59,000 African-American women from all regions of the United States. Individual SES was defined as the participant's self-reported level of education, and neighborhood SES was measured by a score based on census block group data for 6 indicators of income and education. Analyses included 1,343 incident breast cancer cases identified during follow-up from 1995 through 2009. In age-adjusted analyses, SES for both individuals and neighborhoods was associated with an increased incidence of estrogen receptor-positive breast cancer. The associations were attenuated by control for parity and age at first birth, and there was no association after further control for other breast cancer risk factors. These findings suggest that the observed associations of breast cancer with SES may be largely mediated by reproductive factors that are associated with both estrogen receptor-positive breast cancer and SES.

The authors assessed the relation of hormonal and pregnancy-related factors to the incidence of sarcoidosis in the Black Women's Health Study. On biennial questionnaires, participants (US black women aged 21–69 years at baseline) reported data on diagnoses of sarcoidosis, reproductive history, and medication use. Cox regression models, adjusted for age, education, geographic region, smoking, and body mass index, were used to estimate incidence rate ratios and 95% confidence intervals. During 694,818 person-years of follow-up from 1995 through 2009, 452 incident cases of sarcoidosis were identified. The incidence of sarcoidosis decreased as age at menopause increased (P-trend = 0.03). Both later age at first full-term birth and having a more recent birth were associated with a reduced incidence of sarcoidosis. In models that included both factors, the incidence rate ratios were 0.60 (95% confidence interval: 0.37, 0.97) for age at first birth ≥30 years versus

OBJECTIVE: To investigate the association of physical and sexual abuse in childhood and adolescence with risk of adult obesity among black women in the United States. METHODS: Participants were women enrolled in the Black Women’s Health Study, an ongoing prospective cohort study begun in 1995. In 2005, 33 298 participants completed a self-administered questionnaire on early life experiences of abuse. Log-binomial regression models were used to derive risk ratios (RRs) and 95% confidence intervals (CIs) for the relation of child/teenager abuse with obesity (BMI ≥30) and central adiposity (waist circumference >35 inches) reported in 2005. RESULTS: The RR for BMI ≥30, a measure of overall obesity, was 1.29 (95% CI 1.20–1.38) for the highest severity of exposure to child/teenager physical and sexual abuse relative to no abuse. After controlling for postulated intermediates, including reproductive history, diet, physical activity, depressive symptoms, and socioeconomic status, the RR was 1.14 (95% CI 1.08–1.21). The RR for waist circumference >35 inches, which measures central obesity, for severe physical and sexual abuse relative to no abuse was 1.29 (95% CI 1.19–1.38) before adjustment for intermediates and 1.18 (95% CI 1.10–1.27) after adjustment. CONCLUSIONS: Early life sexual and physical abuse was associated with an increased risk of overall and central obesity in adulthood. Although the association between abuse and obesity was explained to some extent by health behaviors, reproductive history, and mental health, these factors did not fully account for the associations. Our data suggest that early life adversity is related to adult body size and weight distribution.

Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited. Objective: We investigated these associations in a pooled analysis of 18 cohort studies. Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model. Results: α-Carotene, β-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER−) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): α-carotene (0.87; 95% CI: 0.78, 0.97), β-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): α-carotene (1.04; 95% CI: 0.99, 1.09), β-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for β-cryptoxanthin were not significant, inverse trends were observed for ER− and ER+ breast cancer (P-trend ≤ 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer. Conclusions: Intakes of α-carotene, β-carotene, and lutein/zeaxanthin were inversely associated with risk of ER−, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources.

A B S T R AC T Recent pooled analyses show an increased risk of death with increasing levels of the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 25.0 or higher in populations of European ancestry, a weaker association among East Asians, and no association of an increased BMI with an increased risk of death among South Asians. The limited data available on blacks indicate that the risk of death is increased only at very high levels of BMI (≥35.0). Methods We prospectively assessed the relation of both BMI and waist circumference to the risk of death among 51,695 black women with no history of cancer or cardiovascular disease who were 21 to 69 years of age at study enrollment. Our analysis was based on follow-up data from 1995 through 2008 in the Black Women’s Health Study. Multivariable proportional-hazards models were used to estimate hazard ratios and 95% confidence intervals. Results Of 1773 deaths identified during follow-up, 770 occurred among 33,916 women who had never smoked. Among nonsmokers, the risk of death was lowest for a BMI of 20.0 to 24.9. For a BMI above this range, the risk of death increased as the BMI increased. With a BMI of 22.5 to 24.9 as the reference category, multivariable-adjusted hazard ratios were 1.12 (95% confidence interval [CI], 0.87 to 1.44) for a BMI of 25.0 to 27.4, 1.31 (95% CI, 1.01 to 1.72) for a BMI of 27.5 to 29.9, 1.27 (95% CI, 0.99 to 1.64) for a BMI of 30.0 to 34.9, 1.51 (95% CI, 1.13 to 2.02) for a BMI of 35.0 to 39.9, and 2.19 (95% CI, 1.62 to 2.95) for a BMI of 40.0 to 49.9 (P

Background: Estrogen receptor (ER)-negative breast tumors and progesterone receptor (PR)-negative breast tumors occur more commonly in women of African ancestry. Recent research indicates that the effects of reproductive factors may differ by hormone receptor status. We assessed the relation of parity and lactation to incidence of ER−/PR− and ER+/PR+ breast cancer in a cohort of African American women. Methods: From 1995–2009, 457 incident cases of ER+/PR+ and 318 cases of ER−/PR− breast cancer were confirmed by review of pathology data among 59,000 African American women followed in the Black Women's Health Study through biennial questionnaires. HRs and two-sided 95% CIs for the incidence of breast cancer subtypes were derived from proportional hazards regression models that controlled for age, reproductive variables, and breast cancer risk factors. Results: Higher parity was associated with an increased risk of ER−/PR− breast cancer (HR = 1.48, 95% CI: 0.98–1.84 for 3+ versus 0 births, Ptrend = 0.009), and with a reduced risk of ER+/PR+ cancer (HR = 0.53, 95% CI: 0.39–0.73 for 3+ versus 0 births, Ptrend = 0.0002). Among women who had breastfed, high parity was no longer associated with increased incidence of ER−/PR− breast, but the inverse association with ER+/PR+ cancer persisted. Conclusions: The higher incidence of ER−/PR− breast cancer in African American women may be explained in part by their higher parity and lower prevalence of breastfeeding relative to white women. Impact: Increased breastfeeding may lead to a reduction in the incidence of this breast cancer subtype. Cancer Epidemiol Biomarkers Prev; 20(9); 1883–91. ©2011 AACR.

Few studies have examined the relation between abuse victimization and breast cancer, and results have been inconclusive. Using data from 35,728 participants in the Black Women's Health Study, we conducted multivariable Cox regression to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CI) for the association of abuse across the life span (childhood, adolescence, and adulthood) with breast cancer. Incident breast cancer diagnoses were reported during 1995-2009, and abuse histories were reported in 2005. No associations were found between abuse victimization in either childhood or adolescence and breast cancer. We found a weak positive association between abuse in adulthood and breast cancer (IRR = 1.18, 95% CI = 1.03-1.34). IRRs for physical abuse only, sexual abuse only, and both physical and sexual abuse in adulthood, relative to no abuse, were 1.28 (95% CI = 1.09-1.49), 0.96 (95% CI = 0.76-1.20), and 1.22 (95% CI = 1.00-1.49), respectively. IRRs for low, intermediate, and high frequencies of physical abuse in adulthood, relative to no abuse, were 1.28 (95% CI = 1.07-1.52), 1.37 (95% CI = 1.04-1.79), and 1.24 (95% CI = 0.95-1.62), respectively. Our data suggest an increased risk of breast cancer among African-American women who reported physical abuse in adulthood, but there was little evidence of a dose-response relation. These results require confirmation in other studies.

Fruits and vegetables are rich sources of carotenoids, flavonoids, and glucosinolates, which are potentially protective against cancer (1–3). Numerous studies have examined the association between fruit and vegetable consumption and breast cancer risk, but results have been inconclusive. A pooled analysis of 8 cohort studies found no overall association between fruit and vegetable intake and breast cancer risk (4). The European Prospective Investigation into Cancer and Nutrition study also had null findings for total fruit and vegetable intake (5). However, there is some evidence that specific subclasses of vegetables, such as cruciferous and carotenoid-rich vegetables, may be inversely associated with risk of breast cancer (6–8). Molecular subtypes of breast cancer may have biologically distinct etiologies (9, 10), and there is increasing evidence that breast cancer risk factors may differ by breast cancer subtype (11–14). Four epidemiologic studies have examined the association between intake of fruits and vegetables and breast cancer risk according to estrogen receptor (ER) or progesterone receptor (PR) status. Two cohort studies reported an inverse association between fruits and vegetables and ER-negative (−) but not ER-positive (+) breast cancer (15, 16), whereas 2 case-control studies observed an inverse association with ER+ but not with ER− breast cancer (17, 18). African-American women are more likely than white women to be diagnosed with ER−/PR− tumors, which are associated with increased 5-year mortality (19). Although black women consume fewer vegetables overall than white women (20), they tend to consume greater amounts of cruciferous vegetables (21). No epidemiologic studies have assessed breast cancer risk in relation to fruit and vegetable intake separately among African-American women. However, in our report from the Black Women's Health Study, we found that a “prudent” dietary pattern—rich in vegetables, fruits, whole grains, and fish—was inversely associated with both premenopausal breast cancer and ER−/PR− breast cancer among African-American women (22), consistent with results from previous studies (23). In the present report, we investigated whether fruit and vegetable intake accounted for the association of breast cancer risk with a prudent dietary pattern in the Black Women's Health Study. In addition, because specific fruits and vegetables may have an important protective effect, we evaluated the relation between subclasses of fruits and vegetables and breast cancer risk.

The authors assessed the utility and cost-effectiveness of using a World Wide Web-based questionnaire in a large prospective cohort study, the Black Women's Health Study (BWHS). In 1995, 59,000 African-American women were recruited into the BWHS through a paper questionnaire. Follow-up paper questionnaires have been mailed every 2 years since then. During the 2003, 2005, and 2007 questionnaire cycles, participants were given the option of completing a Web-based questionnaire. The cost of developing and processing a returned paper questionnaire was 4 times that of a returned Web questionnaire, primarily because of return postage costs and greater processing time for paper questionnaires. The proportion of respondents who completed a Web questionnaire doubled from 2003 to 2007, from 10.1% to 19.9%, but the characteristics of those completing the Web questionnaire remained the same. Web response was greatest at younger ages (20.9% of those aged

Background: Oral contraceptive formulations have changed over time, making it relevant to assess the effect of more recent formulations on breast cancer risk. In addition, some studies have found stronger positive associations of oral contraceptive use with estrogen receptor–negative (ER−) than with ER-positive (ER+) breast cancer. We carried out the first assessment of the effect of oral contraceptive use on the incidence of breast cancer classified by receptor status among African American women, a group disproportionately affected by ER− cancer. Methods: We followed 53,848 Black Women's Health Study participants from 1995 to 2007 through biennial health questionnaires, in which participants reported information about incident breast cancer, oral contraceptive use, and breast cancer risk factors. Pathology information was obtained on receptor status for 789 incident cases. Incidence rate ratios (IRR) with 95% confidence intervals (95% CI) were derived from Cox regression models with control for confounding factors. Results: Ever use of oral contraceptives was more strongly associated with ER−PR− breast cancer (279 cases; IRR, 1.65; 95% CI, 1.19-2.30) than with ER+PR+ cancer (386 cases; IRR, 1.11; 95% CI, 0.86-1.42). The risk of ER−PR− breast cancer increased with increasing duration of use among recent users. Conclusions: These results indicate that the oral contraceptive formulations used in recent decades increase breast cancer risk in African American women, with a greater effect for ER− than ER+ cancer. Impact: Mechanisms to explain the adverse influence of oral contraceptive use on ER− breast cancer need to be elucidated. Cancer Epidemiol Biomarkers Prev; 19(8); 2073–9. ©2010 AACR.

Two single nucleotide polymorphisms (SNPs), rs4415084, and rs10941679 on chromosome 5p12 were associated with risk of breast cancer in a recent genome-wide association study (GWAS) of women of European ancestry. Both SNPs are located in a large high-LD region and the causal variant(s) are still unknown. We conducted a nested case–control study in a cohort of African American women to replicate and narrow the region carrying the causal variant(s). We evaluated 14 tagging SNPs in a 98 kb LD block surrounding the index SNPs in 886 breast cancer cases and 1,089 controls from the Black Women's Health Study. We used the Cochran–Armitage trend test to assess association with breast cancer risk. Odds ratios were derived from logistic regression analyses adjusted for potential confounders including percent European admixture. We confirmed the reported association of rs4415084 SNP with overall risk of breast cancer (P = 0.06), and, as in the original study, observed a stronger association with estrogen receptor positive tumors (P = 0.03). We identified four other SNPs (rs6451770, rs12515012, rs13156930, and rs16901937) associated with risk of breast cancer at the nominal alpha value of 0.05; all of them were located in a 59 kb HapMap YRI LD block. After correction for multiple testing, the association with SNP rs16901937 remained significant (P permutated = 0.038). The G allele was associated with a 21% increased risk of breast cancer overall and with a 32% increase in tumors positive for both estrogen and progesterone receptors. The present results from an African ancestry (AA) population confirm the presence of breast cancer susceptibility genetic variants in the chromosome 5p12 region. We successfully used the shorter range of LD in our AA sample to refine the localization of the putative causal variant.

Diet quality has been inversely associated with overall mortality in white populations, but the evidence in African-American populations is limited.The goal of the present study was to assess diet quality in relation to all-cause mortality in the Black Women's Health Study, a follow-up study of African-American women begun in 1995.Data used in this study were obtained via biennial questionnaires from 1995 to 2011. Based on food-frequency questionnaire data collected in 1995 and 2001, we calculated an index-based diet quality score [Dietary Approaches to Stop Hypertension (DASH)] and derived dietary patterns (prudent and Western) with the use of factor analysis. We followed 37,001 women who were aged 30-69 y and free of cancer, cardiovascular disease, and diabetes at baseline for mortality through 2011. Multivariable Cox regression was used to estimate HRs and 95% CIs. Analyses were conducted in 2014.Based on a total of 1678 deaths during 16 y of follow-up, higher DASH scores were associated with reduced all-cause mortality (HR: 0.75; 95% CI: 0.63, 0.89 for highest vs. lowest quintiles). The DASH components most strongly associated with lower mortality were high intake of whole grains and low intake of red and processed meat. A Western dietary pattern, characterized by high intake of red and processed meat, was associated with increased all-cause mortality rates (HR: 1.37; 95% CI: 1.17, 1.60 for highest vs. lowest quintiles of score); a prudent dietary pattern was not associated with risk.A DASH-style diet high in intake of whole grains and low in consumption of red meat is associated with reduced mortality rates in healthy African-American women.

Background: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee–HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Methods: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Results: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53–0.99; Ptrend cups/day = 3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50–1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55–1.54). There was no association between coffee consumption and ICC. Conclusions: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. Impact: Further research into specific coffee compounds and mechanisms that may account for these associations is needed. Cancer Epidemiol Biomarkers Prev; 24(9); 1398–406. ©2015 AACR.

The human retinoid X receptor β (RXRB) gene maps to the major histocompatibility complex (MHC) region, between KE4 and COL11A2, approximately 130-kb centromeric to HLA-DPB1. We have recently reported a new polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method to detect the G to T single nucleotide polymorphism (SNP) located seven nucleotides after the tenth exon of the RXRB gene, or 3′end+7 position according to existing nomenclature. We also reported strong linkage disequilibrium between the HLA-DPB1*0401 and RXRB+7*T alleles. In the present study, we describe two PCR-RFLP methods to detect additional SNPs in the RXRB gene, T to A, at exon10+378 and A to T at 3′end+140. This new methodology permitted the unambiguous assignment of three distinct SNPs at RXRB exon10+378, 3′end+7 and 3′end+140 to form an “RXRB haplotype.” The data generated from this study were used to determine linkage disequilibrium between several MHC markers and the RXRB alleles and haplotypes. Family studies revealed significant linkage disequilibrium between the RXRB alleles and a number of HLA-DPB1 alleles.

Prenatal DES exposure has been associated with increased risk of breast cancer, but the mechanisms are unknown. Larger bra cup size has also been associated with increased breast cancer risk, although not consistently. We investigated the relation of prenatal DES exposure to mammary gland mass, as estimated by bra cup size. In 2006, 3,222 DES-exposed and 1,463 unexposed women reported their bra cup size, band size (chest circumference), and weight at age 20. Prevalence ratios (PR) were calculated for DES exposure in relation to large bra cup size, with control for year of birth and study cohort. Primary analyses were carried out among women who reported a chest circumference of no more than 32 inches because their cup size would be less influenced by fat mass. Within this group, DES-exposed women had an estimated 45 % increased prevalence (95 % CI 0.97–2.18) of large cup size (C or greater) relative to unexposed women. The PR was further increased among women in this group who had a body mass index of

Risk prediction models for breast cancer are used to counsel women on their individualized risk and determine eligibility for recruitment into prevention trials. The Gail model (1) performs well in white women (2,3) but underestimates risk for black women (4). The Gail model was modified for black women based on data from black women aged 35 to 64 years in the Women’s Contraceptive and Reproductive Experiences (CARE) study (4). The resulting CARE model uses information on a woman’s age, age at menarche, number of previous breast biopsies, and number of first-degree relatives with breast cancer to estimate absolute breast cancer risk over a specified period. In a validation study among postmenopausal black women aged 50 to 79 years in the Women’s Health Initiative (WHI), the model was reported to be well calibrated (ie, the number of observed breast cancers was similar to that predicted by the model), but the average age-specific discriminatory accuracy (ie, the probability that a randomly selected woman with breast cancer has a higher predicted risk than a randomly selected unaffected woman) was only 0.555 (4). The CARE model has yet to be validated among black women aged less than 50 years. Because black women are more likely than white women to be diagnosed with breast cancer before age 40 years (5), it is particularly important to have an effective prediction model for younger black women. In addition, prediction models for breast cancer in black women have not addressed molecular subtypes separately. We used data from the Black Women’s Health Study (BWHS) to assess the calibration and discriminatory accuracy of the CARE model among both younger and older black women and to assess the model’s predictive ability for estrogen receptor–positive (ER+) and estrogen receptor–negative (ER−) breast cancer.

Objectives Early age at natural menopause has been associated with increased all-cause mortality in several studies, although the literature is not consistent. This relation has not been examined among African American women. Study design Data were from the Black Women's Health Study, a follow-up study of African-American women enrolled in 1995. Among 11,212 women who were naturally menopausal at entry to the study or during follow-up through 2008, we assessed the relation of age at natural menopause to all-cause and cause-specific mortality. At baseline and biennially, participants reported on reproductive and medical history, including gynecologic surgeries and exogenous hormone use. Mortality data were obtained from the National Death Index. Multivariable Cox proportional hazard models were used to estimate mortality rate ratios (MRR) and 95% confidence intervals (CI) for categories of age at menopause. Results Of 692 deaths identified during 91,829 person years of follow-up, 261 were due to cancer, 199 to cardiovascular diseases and 232 to other causes. Natural menopause before age 40 was associated with increased all-cause mortality (MRR = 1.34, 95% CI 0.96–1.84, relative to menopause at 50–54 years; P -trend = 0.04) and with the subcategories of death considered – cancer, cardiovascular disease, and all other causes. The associations were present among never and ever users of postmenopausal female hormones and among never and ever smokers. Conclusions In this large prospective cohort of African-American women, natural menopause before age 40 was associated with a higher rate of all-cause and cause-specific mortality. These findings provide support for the theory that natural menopause before age 40 may be a marker of accelerated somatic aging.

The incidence of estrogen receptor positive (ER+) breast cancer is higher among white women relative to black women. In two large prospective cohorts, the Black Women's Health Study (BWHS) and the Nurses' Health Study II (NHSII), we investigated whether reproductive factors explain the difference.During 1,582,083 person-years of follow-up of 140,914 women observed from 1995 to 2007, 327 ER+ breast cancers were identified among black women in BWHS and NHSII and 1,179 among white women in NHSII. Cox proportional hazards regression models, stratified by race and pooled, were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the association of race, parity, age at first birth, and lactation in relation to risk of ER+ cancer with adjustment for age and other breast cancer risk factors.Age at first birth differed markedly in the two groups, with 66 % of parous black women having their first child before age 25 as compared with 36 % of white women. Each additional year of age at first birth was associated with a 4 % increased risk of ER+ breast cancer among both racial groups. Relative to nulliparous women, parous women were at decreased risk of ER+ breast cancer (HR 0.59, 95 % CI 0.20, 1.77), in black women and (HR 0.63, 95 % CI 0.45, 0.87) in white women. The HR for the association of black race with ER+ cancer was 0.67 (95 % CI 0.53, 0.84) in a model that adjusted for age only, 0.77 (95 % CI 0.61, 0.99) in a model that controlled for parity, age at first birth, and other reproductive/hormonal factors, and 0.83 (95 % CI 0.70, 0.98) in a model that additionally controlled for other breast cancer risk factors such as alcohol consumption and use of hormone supplements. Similar associations were seen among premenopausal women and in an analysis restricted to ER+PR+ tumors.Reproductive factors explained some of the higher incidence of ER+ tumors among white women as compared to black women.

Previous studies have suggested that metabolic syndrome may be associated with an increased risk of breast cancer, particularly in postmenopausal women, but U.S. black women have not been assessed. We examined the associations of abdominal obesity, type 2 diabetes, hypertension, and high cholesterol individually and in combination with breast cancer incidence in the Black Women’s Health Study. By means of Cox regression models, we estimated incidence rate ratios (IRR) and 95 % confidence intervals (CI) for the associations of baseline and time-dependent values of self-reported abdominal obesity, type 2 diabetes, hypertension, and high cholesterol with breast cancer incidence. During 516,452 person years of follow-up (mean years = 10.5; standard deviation = 2.9) from 1995 to 2007, 1,228 breast cancer cases were identified. After adjustment for age, education, body mass index at age 18, physical activity, and individual cardiometabolic factors, neither individual nor combinations of cardiometabolic factors were associated with breast cancer incidence overall; the multivariable IRR was 1.04 (95 % CI 0.86–1.25) for the combination of ≥3 factors relative to the absence of all factors, and 1.17 (0.85–1.60) for having all four factors. Among postmenopausal women, however, the comparable IRRs were 1.23 (0.93–1.62) and 1.63 (1.12–2.37), respectively. Our findings provide some support for an association between cardiometabolic factors and breast cancer incidence among postmenopausal U.S. black women.

Epidemiologic studies have yet to provide consistent evidence to support a protective effect of aspirin and other non-steroidal anti-inflammatory drugs (NSAID) on the incidence of breast cancer.We evaluated the relations of current use of aspirin, non-aspirin NSAIDs, and acetaminophen with breast cancer incidence in the Black Women's Health Study.Biennial follow-up of 59,000 study participants began in 1995. During 558,600 person-years of follow-up through 2007, 1,275 breast cancer cases were identified. Using Cox proportional hazards regression, we estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) for associations of current and former use of aspirin, other NSAIDs, and acetaminophen with incident breast cancer.After adjustment for age, education, body mass index at age 18, physical activity, female hormone use, current smoking, and other NSAID use, the IRRs were 0.79 (95% CI = 0.66, 0.95) for current aspirin use and 0.68 (95% CI = 0.50, 0.92) for ≥5 years of aspirin use. Similar associations were observed for acetaminophen use.Both aspirin and acetaminophen use were inversely associated with breast cancer incidence in the present study. Reasons for the association with acetaminophen use are unclear, given that acetaminophen has very weak anti-inflammatory effects.

Background: Numerous studies have reported inverse associations of coffee, tea, and alcohol intake with risk of type 2 diabetes, but none has reported results separately among African American women. Objective: We prospectively examined the relation of coffee, tea, and alcohol consumption to diabetes risk in African American women. Design: The study included 46,906 Black Women's Health Study participants aged 30–69 y at baseline in 1995. Dietary intake was assessed in 1995 and 2001 by using a validated food-frequency questionnaire. During 12 y of follow-up, there were 3671 incident cases of type 2 diabetes. Relative risks (RRs) and 95% CIs were estimated by using Cox proportional hazards models adjusted for diabetes risk factors. Results: Multivariable RRs for intakes of 0–1, 1, 2–3, and ≥4 cups of caffeinated coffee/d relative to no coffee intake were 0.94 (95% CI: 0.86, 1.04), 0.90 (95% CI: 0.81, 1.01), 0.82 (95% CI: 0.72, 0.93), and 0.83 (95% CI: 0.69, 1.01), respectively (P for trend = 0.003). Multivariable RRs for intakes of 1–3, 4–6, 7–13, and ≥14 alcoholic drinks/wk relative to never consumption were 0.90 (95% CI: 0.82, 1.00), 0.68 (95% CI: 0.57, 0.81), 0.78 (95% CI: 0.63, 0.96), and 0.72 (95% CI: 0.53, 0.98), respectively (P for trend < 0.0001). Intakes of decaffeinated coffee and tea were not associated with risk of diabetes. Conclusion: Our results suggest that African American women who drink moderate amounts of caffeinated coffee or alcohol have a reduced risk of type 2 diabetes.

Prospective studies of tea and coffee intake and breast cancer risk have yielded inconsistent results. None of these studies has reported separately on African-American women. We prospectively examined the relation of tea and coffee consumption to risk of breast cancer among 52,062 women aged 21–69 at enrollment in 1995 in the Black Women’s Health Study. Dietary intake was assessed in 1995 and 2001 using a validated food frequency questionnaire. Cox proportional hazards models were used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI), adjusted for breast cancer risk factors. During 12 years of follow-up through 2007, there were 1,268 incident cases of breast cancer. Intakes of tea, coffee, and caffeine were not significantly associated with the risk of breast cancer overall. The IRRs for consumption of ≥4 cups/day compared with none were 1.13 (95% CI 0.78–1.63) for tea and 1.03 (95% CI 0.77–1.39) for caffeinated coffee, and the IRR for the top quintile relative to the bottom quintile of caffeine intake was 1.04 (95% CI 0.87–1.24). Consumption of tea, coffee, and caffeine was not significantly associated with breast cancer risk according to menopausal status or hormone receptor status. Our findings suggest that intakes of tea, coffee, and caffeine are not associated with the risk of breast cancer among African-American women.

Background Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the 1940s70s, has been shown to cause reproductive problems in the daughters. Studies of prenatally-exposed males have yielded conflicting results. Methods In data from a collaborative follow-up of three U.S. cohorts of DES-exposed sons, we examined the relation of prenatal DES exposure to occurrence of male urogenital abnormalities. Exposure status was determined through review of prenatal records. Mailed questionnaires (1994, 1997, 2001) asked about specified abnormalities of the urogenital tract. Risk ratios (RR) were estimated by Cox regression with constant time at risk and control for year of birth. Results Prenatal DES exposure was not associated with varicocele, structural abnormalities of the penis, urethral stenosis, benign prostatic hypertrophy, or inflammation/infection of the prostate, urethra, or epididymus. However, RRs were 1.9 (95% confidence interval 1.13.4) for cryptorchidism, 2.5 (1.54.3) for epididymal cyst, and 2.4 (1.54.4) for testicular inflammation/infection. Stronger associations were observed for DES exposure that began before the 11th week of pregnancy: RRs were 2.9 (1.65.2) for cryptorchidism, 3.5 (2.06.0) for epididymal cyst, and 3.0 (1.75.4) for inflammation/infection of testes. Conclusion These results indicate that prenatal exposure to DES increases risk of male urogenital abnormalities and that the association is strongest for exposure that occurs early in gestation. The findings support the hypothesis that endocrine disrupting chemicals may be a cause of the increased prevalence of cryptorchidism that has been seen in recent years.

Relatively little research has been conducted on familial breast cancer in African American women.Data from the Black Women's Health Study, a prospective cohort study of African American women, were used to assess breast cancer risk in relation to family history of cancer. Since 1995, participants have completed biennial postal questionnaires on health status, risk factors, and family history of cancer. Cox proportional hazards analyses were used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CI) for family history of breast and other types of cancer.Among 57,364 participants who were cancer-free at baseline, 1,306 incident breast cancer cases occurred during 12 years of follow-up. The IRR for a first-degree family history of breast cancer relative to no family history was 1.78 (95% CI 1.55-2.06). IRRs varied by the age at diagnosis, from 1.60 (or=age 55) to 2.76 (age 35). Results were consistent across subtypes of breast tumor defined by estrogen and progesterone receptor status. Breast cancer risk was also associated with family history of colon cancer (IRR 1.35, 95% CI 1.12-1.63) and possibly with family history of leukemia (IRR 1.42, 95% CI 0.82-2.46).These findings indicate a strong familial relationship for breast cancer in African American women. The associations with family history of colon cancer and leukemia warrant further investigation.

Type 2 diabetes mellitus is an increasingly serious health problem among African American women. Consumption of sugar-sweetened drinks was associated with an increased risk of diabetes in 2 studies but not in a third; however, to our knowledge, no data are available on African Americans regarding this issue. Our objective was to examine the association between consumption of sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes mellitus in African American women.A prospective follow-up study of 59,000 African American women has been in progress since 1995. Participants reported on food and beverage consumption in 1995 and 2001. Biennial follow-up questionnaires ascertained new diagnoses of type 2 diabetes. The present analyses included 43,960 women who gave complete dietary and weight information and were free from diabetes at baseline. We identified 2713 incident cases of type 2 diabetes mellitus during 338,884 person-years of follow-up. The main outcome measure was the incidence of type 2 diabetes mellitus.The incidence of type 2 diabetes mellitus was higher with higher intake of both sugar-sweetened soft drinks and fruit drinks. After adjustment for confounding variables including other dietary factors, the incidence rate ratio for 2 or more soft drinks per day was 1.24 (95% confidence interval, 1.06-1.45). For fruit drinks, the comparable incidence rate ratio was 1.31 (95% confidence interval, 1.13-1.52). The association of diabetes with soft drink consumption was almost entirely mediated by body mass index, whereas the association with fruit drink consumption was independent of body mass index.Regular consumption of sugar-sweetened soft drinks and fruit drinks is associated with an increased risk of type 2 diabetes mellitus in African American women. While there has been increasing public awareness of the adverse health effects of soft drinks, little attention has been given to fruit drinks, which are often marketed as a healthier alternative to soft drinks.

The relation of body mass index (BMI) and weight gain to breast cancer risk is complex, and little information is available on Black women, among whom the prevalence of obesity is high. We assessed BMI and weight gain in relation to breast cancer risk in prospective data from the Black Women's Health Study. In 1995, 59,000 African American women enrolled in the Black Women's Health Study by completing mailed questionnaires. Data on anthropometric factors were obtained at baseline and every 2 years afterwards. In 10 years of follow-up, 1,062 incident cases of breast cancer occurred. Incidence rate ratios (IRR) were computed in multivariable Cox proportional hazards regression. BMI at age 18 years of ≥25 relative to

Hair relaxers (straighteners) have been used by millions of African American women, often for many years. Relaxer ingredients can enter the body through scalp lesions and burns. Because manufacturers are not required to list all ingredients, these products may contain unknown harmful substances. We assessed hair relaxer use in relation to breast cancer incidence in the Black Women's Health Study, a nationwide follow-up study of African American women. Information on hair relaxer use was collected in 1997; 48,167 women were followed subsequently through 2003 for incident breast cancer. Incidence rate ratios of breast cancer were estimated with Cox regression. During 266,298 person-years of follow-up, 574 incident cases of breast cancer were ascertained. There were no increases in breast cancer risk associated with any categories of duration of hair relaxer use, frequency of use, age at first use, number of burns experienced during use, or type of relaxer used. The incidence rate ratio for use at least seven times a year for 20 or more years relative to use for less than a year was 0.98 (95% confidence interval, 0.78-1.39). These results suggest that hair relaxer use does not increase the incidence of breast cancer in African American women. (Cancer Epidemiol Biomarkers Prev 2007;16(5):1035–7)

Background: Physical activity is associated with a reduced risk of colon cancer, but the effect of activity on colorectal adenomas, which are precursors to colon cancer, is uncertain. The influence of physical activity on colorectal adenomas among African-American women is of particular interest because African-American women have an increased risk of colon cancer relative to other U.S. women. Methods: We prospectively assessed the relation of physical activity to the incidence of colorectal polyps among African-American women. We followed 45,400 women in the Black Women's Health Study from 1997 to 2003. Data were obtained by biennial mailed questionnaires. During 287,029 person-years of follow-up, 1,390 women reported having been diagnosed with colorectal polyps. A review of medical records of 58 women who reported colorectal polyps indicated that 59% had adenomas and 41% had hyperplastic polyps. We converted hours per week of vigorous exercise and hours per week of walking to metabolic equivalent (MET)-hours. We estimated incidence rate ratios with Cox proportional hazard models, controlling for age, body mass index, smoking, family history of colorectal cancer, and education. Results: For total MET-hours/wk spent in walking and vigorous exercise, the incidence rate ratio decreased from 0.94 for Conclusions: Increased physical activity is associated with a reduced incidence of colorectal polyps among African-American womend. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1438–42)

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 Women's 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/m(2) 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.