Abuse victimization and risk of breast cancer in the Black Women’s Health Study

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.     

Family history of cancer and risk of breast cancer in the Black Women’s Health Study

Introduction  

Relatively little research has been conducted on familial breast cancer in African American women.     

Tea and coffee intake in relation to risk of breast cancer in the Black Women’s Health Study

Objective

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.

Methods

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.

Results

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.

Conclusion

Our findings suggest that intakes of tea, coffee, and caffeine are not associated with the risk of breast cancer among African-American women.     

Consumption of dairy and meat in relation to breast cancer risk in the Black Women’s Health Study

Purpose

Dairy and meat consumption may impact breast cancer risk through modification of hormones (e.g., estrogen), through specific nutrients (e.g., vitamin D), or through products formed in processing/cooking (e.g., heterocyclic amines). Results relating meat and dairy intake to breast cancer risk have been conflicting. Thus, we examined the risk of breast cancer in relation to intake of dairy and meat in a large prospective cohort study.

Methods

In the Black Women’s Health Study, 1,268 incident breast cancer cases were identified among 52,062 women during 12 years of follow-up. Multivariable (MV) relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using Cox proportional hazards models.

Results

Null associations were observed for total milk (MV RR = 1.05, 95 % CI 0.74–1.46 comparing ≥1,000–0 g/week) and total meat (MV RR = 1.04, 95 % CI 0.85–1.28 comparing ≥1,000 < 400 g/week) intake and risk of breast cancer. Associations with intakes of specific types of dairy, specific types of meat, and dietary calcium and vitamin D were also null. The associations were not modified by reproductive (e.g., parity) or lifestyle factors (e.g., smoking). Associations with estrogen receptor (ER) positive (+), ER negative (?), progesterone receptor (PR) +, PR?, ER+/PR+, and ER?/PR? breast cancer were generally null.

Conclusions

This analysis of African-American women provides little support for associations of dairy and meat intake with breast cancer risk.     

Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women’s Health Study

Vitamin D, a prosteroid hormone with anti-proliferative and pro-differentiation activity, is thought to act as a cancer chemopreventive agent. This study evaluated the association between vitamin D intake and breast cancer risk among women in a large prospective cohort study. A total of 34,321 postmenopausal women who had completed a questionnaire that included diet and supplement use were followed for breast cancer incidence from 1986 to 2004. Adjusted relative risks (RR) for breast cancer were calculated for dietary, supplemental, and total vitamin D intake among all women. The adjusted RR of breast cancer for women consuming >800 IU/day versus <400 IU/day total vitamin D was 0.89 (95% CI: 0.77–1.03). RRs were stronger among women with negative than positive ER or PR status. The association of high vitamin D intake with breast cancer was strongest in the first 5 years after baseline dietary assessment (RR = 0.66; 95% CI: 0.46–0.94 compared with lowest-intake group), and diminished over time. Changes in vitamin D intake over time might have contributed to the diminished association observed in later years. Vitamin D intake of >800 IU/day appears to be associated with a small decrease in risk of breast cancer among postmenopausal women. Studies evaluating all sources of vitamin D, especially sun exposure, are needed to fully understand the association between vitamin D and breast cancer risk.     

Menopausal vasomotor symptoms and incident breast cancer risk in the Study of Women’s Health Across the Nation

Purpose

Two case–control studies reported a 50 % decreased breast cancer risk among women who experienced menopausal vasomotor symptoms (VMS), but one cohort study found no association. VMS may be triggered by declining estrogen levels during menopause, whereas elevated estrogen levels have been associated with increased breast cancer risk. VMS may thus be indicative of lower susceptibility to breast cancer.

Methods

We evaluated this relationship in the longitudinal Study of Women’s Health Across the Nation (SWAN), using discrete survival analysis of approximately annual data on VMS and self-reported breast cancer occurrences for up to 13 years of follow-up in 3,098 women who were pre- or early perimenopausal at enrollment.

Results

Over an average 11.4 years of follow-up, 129 incident breast cancer cases were self-reported, and approximately 50 % of participants experienced VMS. Symptomatic women had a reduced risk of breast cancer compared to non-symptomatic women (adjusted HR 0.63, 95 % CI 0.39, 1.00). The association was stronger in the subgroup of women who fully transitioned to postmenopause during follow-up (n = 67 cases, adjusted HR 0.45, 95 % CI 0.26, 0.77).

Conclusion

VMS appeared to be a marker of reduced breast cancer risk. Future research is needed to understand the biology underlying this relationship.

     

Predictors of biospecimen donation in the Black Women’s Health Study

Purpose

Although African-Americans experience higher cancer morbidity and mortality rates compared to their White counterparts, their participation in biospecimen research is lower than that of their white peers. This study investigated the prevalence and predictors of biospecimen donation in a large, cohort study of Black women.

Methods

The BWHS is a follow-up study of U.S. Black women aged 21–69 years enrolled through postal health questionnaires. Between January 2004 and December 2007, participants were sent a consent form with a postage-paid return envelope, and a mouthwash collection kit. Univariate and age- and educational status-adjusted logistic regression models were used to estimate the association of socio-demographic, lifestyle and medical factors with donation of biospecimens.

Results

Buccal cells with consent forms were obtained from 26,790 women, for a response rate of 51 %. The strongest predictors of biospecimen donation were age: response increased from 48.6 % among those aged <40 to 63.1 % among those aged 60 and older [RR 1.30 (95 % CI 1.27, 1.34)]; multivitamin use [RR (95 % CI) 1.32 (1.30, 1.34)]; physician visit in the previous 2 years [RR (95 % CI) 1.61 (1.58, 1.65)], and a history of breast [RR (95 % CI) 1.59 (1.56, 1.63)], colon [RR (95 % CI) 1.18 (1.16, 1.20)], and cervical [RR (95 % CI) 1.63 (1.60, 1.67)] cancer screening.

Conclusions

We found that 51 % of women in the geographically-dispersed Black Women’s Health Study cohort were willing to provide mouthwash samples to be used for genetic analyses. The response in this study is encouraging given published findings of low overall participation rates of African-Americans in genetic studies.

     

Adiponectin pathway polymorphisms and risk of breast cancer in African Americans and Hispanics in the Women’s Health Initiative

Adiponectin, a protein secreted by the adipose tissue, is an endogenous insulin sensitizer with circulating levels that are decreased in obese and diabetic subjects. Recently, circulating levels of adiponectin have been correlated with breast cancer risk. Our previous work showed that polymorphisms of the adiponectin pathway are associated with breast cancer risk. We conducted the first study of adiponectin pathways in African Americans and Hispanics in the Women’s Health Initiative SNP Health Association Resource cohort of 3,642 self-identified Hispanic women and 8,515 self-identified African American women who provided consent for DNA analysis. Single nucleotide polymorphisms (SNPs) from three genes were included in this analysis: ADIPOQ, ADIPOR1, and ADIPOR2. The genome-wide human SNP array 6.0 (909,622 SNPs) (www.affymetrix.com) was used. We found that rs1501299, a functional SNP of ADIPOQ that we previously reported was associated with breast cancer risk in a mostly Caucasian population, was also significantly associated with breast cancer incidence (HR for the GG/TG genotype: 1.23; 95 % CI 1.059–1.43) in African American women. We did not find any other SNPs in these genes to be associated with breast cancer incidence. This is the first study assessing the role of adiponectin pathway SNPs in breast cancer risk in African Americans and Hispanics. RS1501299 is significantly associated with breast cancer risk in African American women. As the rates of obesity and diabetes increase in African Americans and Hispanics, adiponectin and its functional SNPs may aid in breast cancer risk assessment.     

Genetic variants in the H2AFX promoter region are associated with risk of sporadic breast cancer in non-Hispanic white women aged ≤55 years

The histone protein family member X (H2AFX) is important in maintaining chromatin structure and genetic stability. Genetic variants in H2AFX may alter protein functions and thus cancer risk. In this case-control study, we genotyped four common single nucleotide polymorphisms (i.e., -1654A > G [rs643788], -1420G > A [rs8551], and -1187T > C [rs7759] in the H2AFX promoter region and 1057C > T [rs7350] in the 3' untranslated region (UTR)) in 467 patients with sporadic breast cancer and 488 cancer-free controls. All female subjects were non-Hispanic whites aged T polymorphism. Therefore, we believe that H2AFX promoter polymorphisms may contribute to the etiology of sporadic breast cancer in young non-Hispanic white women. Larger association studies and related functional studies are warranted to confirm these findings.     

The effect of genetic variants on the relationship between statins and breast cancer in postmenopausal women in the Women’s Health Initiative observational study

Purpose

Statins have been postulated to have chemopreventive activity against breast cancer. We evaluated whether germline genetic polymorphisms modified the relationship between statins and breast cancer risk using data from the Women’s Health Initiative. We evaluated these interactions using both candidate gene and agnostic genome-wide approaches.

Methods

To identify candidate gene–statin interactions, we tested interactions between 22 SNPS in nine candidate genes implicated in the effect of statins on lipid metabolism in 1687 cases and 1687 controls. We then evaluated statin use interaction with the remaining 30,380 SNPs available in this sample from the CGEMS GWAS study.

Results

After adjusting for multiple comparisons, no SNP interactions with statin usage and risk of breast cancer were statistically significant in either the candidate genes or genome-wide approaches.

Conclusions

We found no evidence of SNP interactions with statin usage for breast cancer risk in a population of 3374 individuals. These results suggest that genome-wide common genetic variants do not moderate the association between statin usage and breast cancer in the population of women in the Women’s Health Initiative.

     

Parity and breastfeeding among African-American women: differential effects on breast cancer risk by estrogen receptor status in the Women’s Circle of Health Study

Purpose

It has long been held that parity reduces risk of breast cancer. However, accumulating evidence indicates that the effects of parity, as well as breastfeeding, may vary according to estrogen receptor (ER) status. We evaluated these associations in a case–control study among African-American women in New York City and New Jersey.

Methods

In the Women’s Circle of Health Study, including 786 African-American women with breast cancer and 1,015 controls, data on reproductive histories were collected from in-person interviews, with tumor characteristics abstracted from pathology reports. We calculated number of live births and months breastfeeding for each child, and examined each in relation to breast cancer by ER status, and for triple-negative (TN) breast cancer.

Results

Although associations were not statistically significant, having children was associated with reduced risk of ER+ breast cancer [odds ratio (OR) 0.82, 95 % confidence interval (CI) 0.58–1.16], but increased risk of ER? tumors, with associations most pronounced for TN breast cancer (OR 1.81, 95 % CI 0.93–3.51). Breastfeeding gave no additional benefit for ER+ cancer, but reduced the risk of ER? disease associated with parity.

Conclusions

Accumulating data from a number of studies, as well as our own in African-American women, indicate that the effects of parity and breastfeeding differ by ER status. African-American women are more likely to have children and not to breastfeed, and to have ER? and TN breast cancer. It is possible that breastfeeding in this population could reduce risk of more aggressive breast cancers.     

Plasma enterolactone and breast cancer risk in the Nurses’ Health Study II

Lignans are plant-based phytoestrogens with both estrogenic and anti-estrogenic properties that may be important for breast carcinogenesis. Retrospective studies have observed decreased breast cancer risk associated with high circulating enterolactone concentrations, a biomarker of lignan intake, but results from prospective studies are conflicting. To prospectively examine this association, we measured plasma enterolactone levels in 802 breast cancer cases and 802 matched controls nested among predominantly premenopausal women in the Nurses’ Health Study II cohort. We used conditional logistic regression and polytomous logistic regression models, adjusting for known breast cancer risk factors, to calculate relative risks (RR) and 95 % confidence intervals (CI). Compared to women with enterolactone concentrations ≤4 nmol/L, the multivariate-adjusted RRs for breast cancer were 1.18 (95 % CI 0.86–1.62), 0.91 (95 % CI 0.66–1.25), and 0.96 (95 % CI 0.70–1.33) for women with enterolactone levels in the second to the fourth quartiles, respectively; P _trend = 0.60. Results were similar across tumors defined by estrogen and progesterone receptor status. Among premenopausal women with follicular estradiol levels below the median (<47 pg/mL), women in the highest category of enterolactone levels had a 51 % lower breast cancer risk compared to those in the lowest category (95 % CI 0.27–0.91); P _trend = 0.02. No association was observed among women with high-follicular estradiol levels (≥47 pg/mL), (comparable RR = 1.39, 95 % CI 0.73–2.65; P _interaction = 0.02). We did not observe an overall association between plasma enterolactone and breast cancer risk in a large nested case–control study of US women. However, a significant inverse association was observed among premenopausal women with low-follicular estradiol levels, suggesting that enterolactone may be important in a low-estrogen environment. This should be confirmed in future studies.     

Theory,methods, and operational results of the Young Women’s Health History Study: a study of young-onset breast cancer incidence in Black and White women

Cancer Causes & Control - The etiology of young-onset breast cancer (BC) is poorly understood, despite its greater likelihood of being hormone receptor-negative with a worse prognosis and...     

Is educational level associated with breast cancer risk in Iranian women?

Background and objective  

A high educational level has been found to be a risk factor of breast cancer. However, it is not clear whether such association persists after adjustment for individual risk factors of breast cancer such as parity in Iranian women.     

Coffee and caffeine intake and the risk of ovarian cancer: the Iowa Women’s Health Study

Laboratory data suggest that caffeine or some components of coffee may cause DNA mutations and inhibit tumor suppressor mechanisms, leading to neoplastic growth. However, coffee consumption has not been clearly implicated in the etiology of human postmenopausal ovarian cancer. This study evaluated the relationship of coffee and caffeine intake with risk of epithelial ovarian cancer in a prospective cohort study of 29,060 postmenopausal women. The participants completed a mailed questionnaire that assessed diet and health history and were followed for ovarian cancer incidence from 1986 to 2004. Age-adjusted and multivariate-adjusted hazard ratios were calculated for four exposure variables: caffeinated coffee, decaffeinated coffee, total coffee, and total caffeine to assess whether or not coffee or caffeine influences the risk of ovarian cancer. An increased risk was observed in the multivariate model for women who reported drinking five or more cups/day of caffeinated coffee compared to women who reported drinking none (HR = 1.81, 95% CI: 1.10–2.95). Decaffeinated coffee, total coffee, and caffeine were not statistically significantly associated with ovarian cancer incidence. Our results suggest that a component of coffee other than caffeine, or in combination with caffeine, may be associated with increased risk of ovarian cancer in postmenopausal women who drink five or more cups of coffee a day.     

Impact of residential UV exposure in childhood versus adulthood on skin cancer risk in Caucasian,postmenopausal women in the Women’s Health Initiative

Background

Sun exposure is a major risk factor for skin cancer; however, the relative contribution of ultraviolet (UV) exposure during childhood versus adulthood on skin cancer risk remains unclear.

Objective

Our goal was to determine the impact of residential UV, measured by AVerage daily total GLObal solar radiation (AVGLO), exposure during childhood (birth, 15 years) versus adulthood (35, 50 years, and present) on incident non-melanoma skin cancer (NMSC) and malignant melanoma (MM) in postmenopausal women.

Methods

Women were followed with yearly surveys throughout the duration of their participation in the Women’s Health Initiative Observational study, a multicenter study from 1993 to 2005. A total of 56,557 women had data on all observations and were included in the baseline characteristics. The main exposure, residential UV (as measured by AVGLO), was measured by geographic residence during childhood and adulthood. Outcome was risk of incident NMSC and MM.

Results

Over 11.9 years (median follow-up), there were 9,195 (16.3 %) cases of NMSC and 518 (0.92 %) cases of MM. Compared with the reference group (women with low childhood and low adulthood UV), women with low childhood and high adulthood UV had a 21 % increased risk of NMSC (odds ratio 1.21, 95 % confidence interval 1.12, 1.31). Women with high childhood and high adulthood UV had a 19 % increased risk of NMSC (odds ratio 1.19, 95 % confidence interval 1.11, 1.27). Surprisingly, women with high childhood UV and low adulthood UV did not have a significant increase in NMSC risk compared with the reference group (odds ratio 1.08, 95 % confidence interval 0.91, 1.28) in multivariable models. Residential UV exposure in childhood or adulthood was not associated with increased melanoma risk.

Conclusion

This study reveals an increase in NMSC risk associated with adulthood residential UV exposure, with no effect for childhood UV exposure.

     

Cigarette smoking and risk of benign proliferative epithelial disorders of the breast in the Women’s Health Initiative

Objective To investigate the association between cigarette smoking and risk of benign proliferative epithelial disorders (BPED) of the breast. Methods We used data from an ancillary study of benign breast disease that is being conducted in the Women’s Health Initiative randomized clinical trials among 68,132 postmenopausal women aged 50–79 at recruitment. After following the trial participants for an average of 7.8 years, we had ascertained 294 incident cases with atypical hyperplasia and 1,498 incident cases with non-atypical BPED of the breast. We used Cox proportional hazards models to estimate hazard ratios for the association between cigarette smoking and risk of BPED. Results Smoking measures, including duration of smoking, intensity of smoking, pack-years of smoking, age at which smoking commenced, and years since quitting smoking, were not associated with risk of BPED overall or by histological subtypes. Conclusion The null association between cigarette smoking and risk of BPED of the breast suggests that the carcinogenic and antiestrogenic effects of cigarette smoking on the breast might counterbalance each other and that cigarette smoking might have no overall effects on BPED of the breast among postmenopausal women.