Selected antioxidants and risk of hormone receptor-defined invasive breast cancers among postmenopausal women in the Women's Health Initiative Observational Study

BACKGROUND: Few studies have evaluated carotenoids and vitamins C and E in association with the risk of breast cancers defined by estrogen receptor (ER) and progesterone receptor (PR) status. OBJECTIVE: We examined the associations between dietary and supplemental intakes of these nutrients and risk of breast cancers jointly defined by both ER and PR status among postmenopausal women. DESIGN: Our investigation was conducted in the Women's Health Initiative Observational Study. After following 84 805 women for an average of 7.6 y, 2879 incident invasive breast cancer cases had been ascertained, of whom 2509 had receptor data. We used Cox proportional hazards models to assess the associations of interest. RESULTS: Dietary alpha-carotene (highest versus lowest quintile: RR = 0.83; 95% CL = 0.70, 0.99; P for trend = 0.019), beta-carotene (highest versus lowest quintile: RR = 0.78; 95% CL = 0.66, 0.94; P for trend = 0.021), and lycopene (highest versus lowest quintile: RR = 0.85; 95% CL = 0.73, 1.00; P for trend = 0.064) were inversely associated with risk of ER+PR+breast cancer, but not with other breast cancer groups jointly defined by ER and PR status. Total or supplemental beta-carotene and dietary intakes of lutein+zeaxanthin and beta-cryptoxanthin were not associated with breast cancers defined by ER and PR status. Vitamin E (regardless of source) and dietary vitamin C were not associated with breast cancer. However, total and supplemental vitamin C intake had weak positive associations with breast cancer overall. CONCLUSION: Dietary intake of certain carotenoids might be differentially associated with risk of invasive breast cancers jointly defined by ER and PR status among postmenopausal women.     

Frequency of private spiritual activity and cardiovascular risk in postmenopausal women: the Women's Health Initiative

PurposeSpirituality has been associated with better cardiac autonomic balance, but its association with cardiovascular risk is not well studied. We examined whether more frequent private spiritual activity was associated with reduced cardiovascular risk in postmenopausal women enrolled in the Women's Health Initiative Observational Study.MethodsFrequency of private spiritual activity (prayer, Bible reading, and meditation) was self-reported at year 5 of follow-up. Cardiovascular outcomes were centrally adjudicated, and cardiovascular risk was estimated from proportional hazards models.ResultsFinal models included 43,708 women (mean age, 68.9 ± 7.3 years; median follow-up, 7.0 years) free of cardiac disease through year 5 of follow-up. In age-adjusted models, private spiritual activity was associated with increased cardiovascular risk (hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.02–1.31 for weekly vs. never; HR, 1.25; 95% CI, 1.11–1.40 for daily vs. never). In multivariate models adjusted for demographics, lifestyle, risk factors, and psychosocial factors, such association remained significant only in the group with daily activity (HR, 1.16; 95% CI, 1.03–1.30). Subgroup analyses indicate this association may be driven by the presence of severe chronic diseases.ConclusionsAmong aging women, higher frequency of private spiritual activity was associated with increased cardiovascular risk, likely reflecting a mobilization of spiritual resources to cope with aging and illness.     

Dietary patterns are associated with disease risk among participants in the Women's Health Initiative Observational Study

Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women's Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infarct compared to 1224 WHI-OS controls matched for age, enrollment date, race/ethnicity, and absence of CHD at baseline or follow-up. The first six principal components explained >75% of variation in dietary intakes and K-mean analysis based on these six components produced three clusters. Diet cluster 1 was rich in carbohydrate, vegetable protein, fiber, dietary vitamin K, folate, carotenoids, α-linolenic acid [18:3(n-3)], linoleic acid [18:2(n-6)], and supplemental calcium and vitamin D. Diet cluster 2 was rich in total and animal protein, arachidonic acid [20:4(n-6)], DHA [22:6(n-3)], vitamin D, and calcium. Diet cluster 3 was rich in energy, total fat, and trans fatty acids (all P < 0.01). Conditional logistic regression analysis demonstrated diet cluster 1 was associated with lower CHD risk than diet cluster 2 (reference group) adjusted for smoking, education, and physical activity [OR = 0.79 (95% CI = 0.64, 0.99); P = 0.038]. This difference was not significant after adjustment for BMI and systolic blood pressure. Diet cluster 3 was associated with higher CHD risk than diet cluster 2 [OR = 1.28 (95% CI = 1.04, 1.57); P = 0.019], but this difference did not remain significant after adjustment for smoking, education, and physical activity. Within this WHI-OS cohort, distinct dietary patterns may be associated with subsequent CHD outcomes.     

Interaction of nitrate and folate on the risk of breast cancer among postmenopausal women

Ingested nitrate can be endogenously reduced to nitrite, which may form N-nitroso compounds, known potent carcinogens. However, some studies have reported no or inverse associations between dietary nitrate intake and cancer risk. These associations may be confounded by a protective effect of folate, which plays a vital role in DNA repair. We evaluated the interaction of dietary and water nitrate intake with total folate intake on breast cancer risk in the Iowa Women's Health Study. Dietary intake was assessed at study baseline. Nitrate intake from public water was assessed using a historical database on Iowa municipal water supplies. After baseline exclusions, 34,388 postmenopausal women and 2,875 incident breast cancers were included. Overall, neither dietary nor water nitrate was associated with breast cancer risk. Among those with folate intake ≥400 μg/day, breast cancer risk was significantly increased in public water users with the highest nitrate quintile (HR = 1.40, 95% CI = 1.05-1.87) and private well users (HR = 1.38, 95% CI = 1.05-1.82) compared to public water users with the lowest nitrate quintile; in contrast, there was no association among those with lower folate intake. Our findings do not support a previous report of increased risk of breast cancer among individuals with high dietary nitrate but low folate intake.     

Alcohol consumption and the risk of coronary heart disease in postmenopausal women with diabetes: Women’s Health Initiative Observational Study

Background  

Although several observational studies have consistently reported an inverse association between moderate alcohol consumption and risk of coronary heart disease (CHD), it is yet not well established if this association also exists among people with type 2 diabetes. The aim of this study is to evaluate the association between the frequency and quantity of alcohol intake and the risk of developing CHD among postmenopausal women with diabetes.     

Association of glycemic load with cardiovascular disease risk factors: The Women's Health Initiative Observational Study

ObjectiveAssociations between dietary glycemic load (GL) and cardiovascular disease risk factors, including plasma lipoprotein/lipid levels, blood pressure, and glucose metabolism factors, in the Women's Health Initiative Observational Study were examined.MethodsA random sample of 878 Observational Study participants (postmenopausal women 50–79 y of age) with baseline blood measurements (647 white, 104 black, 127 Hispanic) was included. Dietary GL was estimated from baseline food-frequency questionnaires, which assessed dietary intake over the previous 3 mo. At the baseline visit, participants completed demographic and health habit questionnaires, fasting blood samples were collected, anthropometric measurements were completed, and blood pressure was assessed.ResultsIn all participants combined, GL was inversely associated with high-density lipoprotein cholesterol (P for trend = 0.004) and positively associated with log₁₀-transformed triacylglycerols (P = 0.008). Although there were no statistically significant interactions of race/ethnicity with associations between GL and cardiovascular disease risk factors, stratified results were suggestive, showing that GL was positively associated with total cholesterol (P = 0.018) and low-density lipoprotein cholesterol (P = 0.038) in Hispanics. In white subjects, there was a trend of reduced high-density lipoprotein cholesterol with higher GL (P = 0.003), whereas GL was positively associated with log₁₀-transformed triacylglycerols (P = 0.015). Associations between GL and high-density lipoprotein cholesterol and between GL and triacylglycerols also differed by body mass index, although the interactions were not statistically significant.ConclusionAmong these generally healthy postmenopausal women, GL was associated with high-density lipoprotein cholesterol and triacylglycerols. Suggestive effects of race/ethnicity and body mass index on these associations need to be confirmed in larger studies.     

Body size, weight cycling, and risk of renal cell carcinoma among postmenopausal women: the Women's Health Initiative (United States)

Although obesity is an established risk factor for renal cell carcinoma, the possible effect of central adiposity and long-term variation in weight has yet to be established. The authors studied 140,057 women aged 50-79 years enrolled in the Women's Health Initiative in the United States to examine the role of obesity, especially abdominal obesity, and weight cycling in relation to risk of renal cell carcinoma among postmenopausal women. Cox models were used to estimate relative risks and their corresponding 95% confidence intervals. During an average of 7.7 years of follow-up through September 12, 2005, a total of 269 incident cases of renal cell carcinoma were identified. Central adiposity, as indicated by waist-to-hip ratio, was an important risk factor for developing renal cell carcinoma (highest vs. lowest quartile: relative risk = 1.8, 95% confidence interval: 1.2, 2.5; p for trend = 0.0003). Moreover, women who had experienced weight cycling more than 10 times were at 2.6 times (95% confidence interval: 1.6, 4.2) increased risk compared with women whose weight was stable. Results add evidence that obesity, particularly central adiposity, is associated with an increased risk of renal cell carcinoma among postmenopausal women. Furthermore, they indicate that weight cycling is independently associated with further increased risk of this malignancy.     

Association between childhood socioeconomic status and coronary heart disease risk among postmenopausal women: findings from the British Women's Heart and Health Study

OBJECTIVES: We assessed the association between childhood socioeconomic status (SES) and coronary heart disease among postmenopausal women. METHODS: We conducted a cross-sectional analysis of 3444 women aged 60 to 79 years. RESULTS: There was an independent linear association between childhood and adult SES and coronary heart disease. The association between childhood SES and coronary heart disease was attenuated when we adjusted for insulin resistance syndrome, adult smoking, physical activity, biomarkers of childhood nutrition, and passive smoking. CONCLUSIONS: The association between adverse childhood SES and coronary heart disease is in part mediated through insulin resistance, which may be influenced by poor childhood nutrition, and in part through the association between childhood SES and adult behavioral risk factors.     

Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study

OBJECTIVE: Systemic inflammation may play an important role in the development of atherosclerosis, type 2 diabetes, and some cancers. Few studies have comprehensively assessed the direct relations between dietary fiber and inflammatory cytokines, especially in minority populations. Using baseline data from 1958 postmenopausal women enrolled in the Women's Health Initiative Observational Study, we examined cross-sectional associations between dietary fiber intake and markers of systemic inflammation (including serum high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], and tumor necrosis factor-alpha receptor-2 [TNF-alpha-R2]) in addition to differences in these associations by ethnicity. METHODS: Multiple linear regression models were used to assess the relation between fiber intake and makers of systemic inflammation. RESULTS: After adjustment for covariates, intakes of dietary fiber were inversely associated with IL-6 (P values for trend were 0.01 for total fiber, 0.004 for soluble fiber, and 0.001 for insoluble fiber) and TNF-alpha-R2 (P values for trend were 0.002 for total, 0.02 for soluble, and <0.001 for insoluble fibers). Although the samples were small in minority Americans, results were generally consistent with those found among European Americans. We did not observe any significant association between intake of dietary fiber and hs-CRP. CONCLUSION: These findings lend support to the hypothesis that a high-fiber diet is associated with lower plasma levels of IL-6 and TNF-alpha-R2. Contrary to previous reports, however, there was no association between fiber and hs-CRP among postmenopausal women. Future studies on the influence of diet on inflammation should include IL-6 and TNF-alpha-R2 and enroll participants from ethnic minorities.     

Alcohol consumption and breast cancer risk in the Women's Health Study

The authors assessed the association between moderate alcohol consumption and breast cancer risk in the Women's Health Study (United States, 1992-2004). During an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190 invasive and 294 in situ) were documented among 38,454 women who, at baseline, were free of cancer and cardiovascular disease and provided detailed dietary information, including alcohol consumption, for the preceding 12 months. Higher alcohol consumption was associated with a modest increase in breast cancer risk; the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32 (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95% CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the multivariable relative risks for an increment of 10 g/day of alcohol were 1.11 (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167 cases). The association also seemed strongest among those taking postmenopausal hormones currently, but the test for interaction was not significant. The findings from this prospective study suggest that moderate alcohol consumption increases breast cancer risk.     

Antioxidant supplements and risk of breast cancer recurrence and breast cancer-related mortality among postmenopausal women

Despite widespread use, only a few clinical or epidemiological studies have examined the relationship between antioxidant supplements and risk of breast cancer recurrence or breast cancer-related mortality. We used proportional hazards and logistic regression modeling to estimate rate ratios and odds ratios (ORs) for recurrence and mortality among 385 postmenopausal women diagnosed with breast cancer between 1986 and 1988 enrolled into a case-control study on diet and cancer. Women were recontacted with a single questionnaire to ascertain the use of nutritional supplements during 12-14 yr of follow-up time. In multivariable models, antioxidant supplement users compared with nonusers were less likely to have a breast cancer recurrence or breast cancer-related death (OR = 0.54, 95% CI = 0.27-1.04). Vitamin E supplements showed a modest protective effect when used for more than 3 yr (OR = 0.33, 95% CI = 0.10-1.07). Premorbid dietary intake of vitamins C or E from diet, supplements, or both showed no relationship with risk. Risks of recurrence and disease-related mortality were reduced among women using vitamin C and vitamin E supplements for more than 3 yr. Recall bias among proxy respondents for women who died during follow-up may have contributed to these findings. This study provides limited support for the hypothesis that antioxidant supplements may reduce the risk of breast cancer recurrence or breast cancer-related mortality.     

The DHHS Office on Women's Health Initiative to Improve Women's Heart Health: focus on knowledge and awareness among women with cardiometabolic risk factors

Abstract Background: The diversity of the U.S. population and disparities in the burden of cardiovascular disease (CVD) require that public health education strategies must target women and racial/ethnic minority groups to reduce their CVD risk factors, particularly in high-risk communities, such as women with the metabolic syndrome (MS). Methods: The data reported here were based on a cross-sectional face-to-face survey of women recruited from four participating sites as part of the national intervention program, Improving, Enhancing and Evaluating Outcomes of Comprehensive Heart Care in High-Risk Women. Measures included baseline characteristics, sociodemographics, CVD related-knowledge and awareness, and Framingham risk score (FRS). Results: There were 443 of 698 women (63.5%) with one or more risk factors for the MS: non-Hispanic white (NHW), 51.5%; non-Hispanic black (NHB), 21.0%; Hispanic, 22.6%. Greater frequencies of MS occurred among Hispanic women (p<0.0001), those with less than a high school education (70.0%) (p<0.0001), Medicaid recipients (57.8%) (p<0.0001), and urbanites (43.3%) (p<0.001). Fewer participants with MS (62.6%) knew the leading cause of death compared to those without MS (72.1%) (p<0.0001). MS was associated with a lack of knowledge of the composite of knowing the symptoms of a heart attack plus the need to call 911 (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.17-0.97, p=0.04). Conclusions: Current strategies to decrease CVD risk are built on educating the public about traditional factors, including hypertension, smoking, and elevated low-density lipoprotein cholesterol (LDL-C). An opportunity to broaden the scope for risk reduction among women with cardiometabolic risk derives from the observation that women with the MS have lower knowledge about CVD as the leading cause of death, the symptoms of a heart attack, and the ideal option for managing a CVD emergency.     

Conjugated equine estrogens and breast cancer risk in the Women's Health Initiative clinical trial and observational study

The Women's Health Initiative randomized controlled trial found a trend (p = 0.09) toward a lower breast cancer risk among women assigned to daily 0.625-mg conjugated equine estrogens (CEEs) compared with placebo, in contrast to an observational literature that mostly reports a moderate increase in risk with estrogen-alone preparations. In 1993-2004 at 40 US clinical centers, breast cancer hazard ratio estimates for this CEE regimen were compared between the Women's Health Initiative clinical trial and observational study toward understanding this apparent discrepancy and refining hazard ratio estimates. After control for prior use of postmenopausal hormone therapy and for confounding factors, CEE hazard ratio estimates were higher from the observational study compared with the clinical trial by 43% (p = 0.12). However, after additional control for time from menopause to first use of postmenopausal hormone therapy, the hazard ratios agreed closely between the two cohorts (p = 0.82). For women who begin use soon after menopause, combined analyses of clinical trial and observational study data do not provide clear evidence of either an overall reduction or an increase in breast cancer risk with CEEs, although hazard ratios appeared to be relatively higher among women having certain breast cancer risk factors or a low body mass index.     

Vigorous leisure activity through women's adult life: the Women's Health Initiative Observational Cohort Study

This study described differences in vigorous activity participation recalled across the life span, assessed whether reports of past vigorous activity were associated with current participation, and examined factors associated with participation in current vigorous activity among women. After the exclusion of women aged 50-54 years, the study population included 71,837 multiethnic postmenopausal women aged 55-79 years who were participating in the Women's Health Initiative Observational Cohort Study, 1993-1998. Vigorous activity was assessed retrospectively for ages 18, 35, and 50 years and currently at enrollment into the study (median age, 65 years). Current participation in vigorous activity (>3 days/week) was low and consistent across racial/ethnic groups (13-16%). The prevalence of vigorous activity declined with age, with the largest decrease in vigorous activity occurring after age 50 years for all racial/ethnic groups. Current vigorous activity was generally higher among women with a lower body mass index, not currently smoking, in excellent general health, and of higher socioeconomic status across racial/ethnic groups. These data suggest that a lower prevalence of vigorous activity in the postmenopausal period is part of a complex of health-related attitudes and behaviors that transcends race/ethnicity. The perimenopausal period may be a critical juncture at which targeted and tailored interventions may help to achieve maintenance of physical activity into the postmenopausal period.     

Folate intake, alcohol and risk of breast cancer among postmenopausal women in Denmark

OBJECTIVE: There is consistent evidence that alcohol increases the risk of breast cancer. It has been suggested that the increased risk associated with alcohol intake may be reduced by adequate intake of folate. Since many women consume alcohol, detection of a risk-reducing mechanism would have major public health implications. DESIGN: We therefore evaluated the possible interaction between alcohol and folate in a paired nested case-control study among postmenopausal women. SETTING: A total of 24 697 postmenopausal women were included in the 'Diet, Cancer and Health' follow-up study between December 1993 and May 1997. The cohort was followed until December 2000. The study included 388 cases of breast cancer and 388 randomly selected controls were used to estimate the breast cancer incidence rate ratio (IRR) in conditional logistic regression analysis. RESULTS: A previously established association between alcohol intake and risk of breast cancer was present mainly among women with low folate intake. An IRR of 1.19 (95% CI: 0.99-1.42) per 10 g average daily alcohol intake was found for women with a daily folate intake below 300 mug, while among women with a folate intake higher than 350 mug, we could not show an association between the alcohol intake and the breast cancer incidence rate (e.g. folate intake >400 mug; IRR of 1.01 (95% CI: 0.85-1.20)). CONCLUSION: The findings support the evidence that adequate folate intake may attenuate the risk of breast cancer associated with high alcohol intake. SPONSORSHIP: The Danish Cancer Society.     

Dietary glycemic load, glycemic index, and carbohydrate and risk of breast cancer in the Women's Health Initiative

Dietary glycemic load (GL), glycemic index (GI), and carbohydrate could be associated with breast cancer risk by influencing long-term blood glucose and insulin concentrations. We examined associations between GL, GI, and carbohydrate and incident breast cancer in 148,767 Women's Heath Initiative (WHI) participants. Dietary variables were estimated from food frequency questionnaires administered at baseline. Self-reported breast cancers during follow-up were confirmed by medical records review. Cox proportional hazards regression modeled time to breast cancer within quintiles of GL, GI, and carbohydrate. There were 6,115 total breast cancers after a median follow-up of 8.0 yr. We observed no associations between GL, GI, or carbohydrate and total incident breast cancer, with hazard ratios and 95% confidence intervals for the highest vs. lowest quintiles of 1.08, 0.92-1.29 (P for trend = 0.27); 1.01, 0.91-1.12 (P = 0.74); and 0.95, 0.80-1.14 (P = 0.98), respectively. There was a trend toward significance for the positive association between GL and in situ cancers (1.40, 0.94-2.13; P = 0.07). Although there was no evidence of associations between GL, GI, or carbohydrate and total breast cancer risk in WHI participants, the suggestion of an association between GL and risk of in situ cancers requires further investigation.