Postmenopausal Hormone Use Research Articles

Dietary advanced glycation end products (AGEs) and breast cancer mortality in the women’s health initiative (WHI).

1570 Background: Breast cancer (BrCa) is the second leading cause of cancer death and constitutes about 14% of total cancer deaths among US women. Advanced glycation end-products (AGEs) are implicated in chronic diseases including cancer and cardiovascular diseases (CVD). AGEs are naturally found in animal products and processed foods, and preparing food at high temperatures increases AGE formation. Our goal was to assess the association between post-diagnosis dietary NƐ-carboxymethyl-lysine (CML)-AGE intake, a common measure of AGE, and mortality from all-causes, BrCa and CVD among participants with invasive BrCa in the Women’s Health Initiative (WHI). Methods: The WHI enrolled postmenopausal women aged 50 to 79 years from 1993-1998 into randomized controlled trials and a prospective observational study to examine causes of morbidity and mortality. In this analysis, we included 2,073 women diagnosed with invasive BrCa during follow-up who completed a food frequency questionnaire (FFQ) after diagnosis, had energy intakes between ≥600 kcal/day and ≤5000 kcal/day, and had CML-AGE intake data available. Women were followed from BrCa diagnosis until death or censoring through March 2018. Cox proportional hazards regression models estimated the hazard ratios (HR) and 95% CIs of mortality risk from all-causes, BrCa and CVD by tertiles of dietary CML-AGE intake with adjustment for age, income, race/ethnicity, study arm, time from diagnosis to FFQ completion, education, physical activity, smoking, BMI, ER/PR status, diagnosis stage, postmenopausal hormone use, intake of energy, alcohol, fat, red and processed meats. Results: After a median 15.1 years of follow-up, 642 deaths were reported including 198 BrCa-specific and 129 CVD-specific deaths. The average time from BrCa diagnosis to FFQ completion was 1.5 years. Compared to the lowest tertile of CML-AGE intake, there was an increased risk in the highest tertile for all-cause mortality (HR: 1.51, 95% CI: 1.17-1.94), BrCa (HR: 1.86, 95% CI: 1.19-2.91) and CVD (HR: 2.14, 95% CI: 1.19-3.84) mortality. Conclusions: Higher dietary AGE intake after BrCa diagnosis in postmenopausal women was associated with increased risk of mortality from all-causes, BrCa and CVD. Exposure to AGEs could be modified through dietary counseling and evaluated in relation to reduced mortality risk after BrCa diagnosis.

The impact of hormones and reproductive factors on the risk of bladder cancer in women: results from the Nurses’ Health Study and Nurses’ Health Study II

With three out of four new bladder cancer (BCa) cases occurring in men, an apparent gender disparity exists. We aimed to investigate the role of hormonal and reproductive factors in BCa risk using two large female US prospective cohorts. Our study population comprised 118256 and 115383 female registered nurses who were recruited in the Nurses' Health Study (NHS) and NHS II, respectively. Reproductive and hormonal factors and other relevant data were recorded in biennial self-administered questionnaires. Cox-regression analyses were performed to estimate age- and multivariable-adjusted incidence risk ratios (IRRs) and 95% confidence intervals (CIs). Inverse-variance-weighted meta-analysis was used to pool estimates across cohorts. During up to 36 years of follow-up, 629 incident BCa cases were confirmed. In the NHS, 22566 women (21.3%) were postmenopausal at baseline, compared with 2723 women (2.4%) in the NHS II. Among women in the NHS, younger age at menopause (≤45 years) was associated with an increased risk of BCa (IRR: 1.41, 95% CI: 1.11-1.81, Ptrend = 0.01) compared with those with menopause onset at age 50+ years, particularly among ever-smokers (IRR for age at menopause ≤45 years: 1.53, 95% CI: 1.15-2.04; PIntx = 0.16). Age at menarche and first birth, parity, oral-contraceptive use and postmenopausal hormone use were not associated with BCa risk. Overall, we found little support for an association between female reproductive factors and BCa risk in these prospective cohort studies. Earlier age at menopause was associated with a higher risk of BCa, particularly among smokers, indicating the potential for residual confounding.

Associations of dairy intake with risk of mortality in women and men: three prospective cohort studies

ObjectiveTo examine the association of consumption of dairy foods with risk of total and cause specific mortality in women and men.DesignThree prospective cohort studies with repeated measures of diet and...

The association of age at menopause and all-cause and cause-specific mortality by race, postmenopausal hormone use, and smoking status.

While a mean age at menopause of 51 years has been reported in the United States (U.S.), some U.S. women experience menopause before age 45, possibly increasing risk of cardiovascular mortality; however, the role in all-cause and cerebrovascular-related mortality is unclear. The purpose of this study was to investigate the association between age at menopause and all-cause and cause-specific mortality by race, hormone replacement therapy (HRT) use, and smoking status. REasons for Geographic and Racial Differences in Stroke (REGARDS) is a population-based study of 30,239 participants aged ≥45 years enrolled between 2003 and 2007 of whom 14,361 were postmenopausal women. Age at menopause was defined as <45 (early) or ≥45. All-cause and cause-specific mortality were ascertained through 2013. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between age at menopause and mortality, adjusting for baseline measures. Of 11,287 eligible women (6403 white; 4884 black), mean menopause age was 45.2 (SD 7.9) with 1524 deaths over 7.1 years. Significant interactions were detected between early age at menopause (39%) and HRT use in association with all-cause mortality (p < 0.01), mortality from coronary heart disease (p = 0.06), and mortality from all other causes (p = 0.04). An association between early age at menopause and all-cause mortality was observed among ever-HRT users (HR = 1.31, 95% CI: 1.10–1.56), but not never-HRT users (HR = 1.01, 95% CI: 0.85–1.20). There were no differences in associations examined by race or smoking status. Increased all-cause mortality risk was observed for ever-HRT users with menopause before age 45.

The association between female hormonal supplementation and molecular types in colorectal cancer.

e15133 Background: In the US, colorectal cancer is the third most common malignancy in women. Postmenopausal hormone use has been associated with decrease in incidence of colorectal cancer however few studies have evaluated the relationship between hormone use and molecular profiles of advanced colorectal cancer. The aim of this study is to evaluate correlations between female hormonal supplementation use and colorectal cancer molecular, clinical, and pathologic features. Methods: We conducted a retrospective case-case study of female patients with metastatic or unresectable, locally advanced colorectal cancer on the Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC) protocol from 2010 to 2017. Post-menopausal hormone use was self-reported in an environmental survey as part of the ATTACC protocol. Molecular, clinical, and pathologic features were obtained through medical record review. Results: Among 258 female patients, 163 (63%) patients reported ever use of female hormonal supplementation. Ever use was significantly associated with BRAF V600E mutant tumors (OR 2.63, p-value 0.04). There was no association with KRAS, NRAS, PIK3CA mutations, microsatellite instability, or CpG island methylation. The mean age at diagnosis of ever users was 54.4 and mean of no supplement was 56.5 (p-value 0.07), indicating no age difference between ever and never users. Conclusions: Despite the overall protective effects of postmenopausal hormone use on colorectal cancer incidence, among those who develop colorectal cancer, our data suggest an association between female hormonal supplementation and BRAF mutation. Further studies are needed to evaluate this relationship in additional cohorts, interrogate the biological basis, and identify whether there is an association with survival of patients with metastatic or locally advanced colorectal cancer with estrogen or progestin supplement use.

Abstract MP38: Association of Changes in Plant-Based Diet Indices with Total and Cause-Specific Mortality

Introduction: Plant-based diets have been associated with health benefits, including lower risk of type 2 diabetes (T2D) and coronary heart disease (CHD). However, the association between plant-based diets and mortality remains unclear as previous studies did not take into account the quality of plant-based foods. To overcome this limitation, we recently developed three plant-based diet indices—an overall plant-based diet index (PDI), a healthful plant-based diet index (hPDI), and an unhealthful plant-based diet index (uPDI, emphasizing processed carbohydrates and fats)—and reported that hPDI and uPDI were differentially associated with T2D and CHD. In this study, we investigate associations between long-term changes in plant-based diet indices and subsequent total and cause-specific mortality in the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). Hypothesis: We hypothesized that improved plant-based diet quality is associated with lower total and cardiovascular disease (CVD) mortality. Method: We included 47,983 women, aged 63±7y (mean±SD) in the NHS and 25,737 men, aged 63±9y in the HPFS who had no history of CVD or cancer on or before 1998 (baseline). We used multivariable Cox proportional-hazards regression to assess the association between 12-y pre-baseline changes (1986-1998) in three plant-based diet indices and subsequent total and cause-specific mortality (1998-2014). We adjusted for age, race, initial corresponding plant-based diet index score, BMI, family history of diabetes, myocardial infarction, or cancer, history of hypertension, hypercholesterolemia, or T2D, medications, postmenopausal status and postmenopausal hormone use in women, initial and 12-y pre-baseline changes in weight and other lifestyle-related factors. Results: Compared with those participants whose diets remained relatively stable during the pre-baseline 12-year period, among participants with the greatest increase in plant-based diet indices, the pooled hazard ratio (95% confidence interval [CI]) for total mortality was 0.92 (95% CI, 0.87 to 0.97) for PDI, 0.90 (95% CI, 0.86 to 0.95) for hPDI, and 1.11 (95% CI, 1.05 to 1.16) for uPDI. For CVD-specific mortality, a 10-point increase in hPDI was associated with a 10% lower risk (95% CI, 5 to 15), while a 10-point increase in uPDI was associated with a 6% higher risk (95% CI, 0 to 12). We found no evidence for changes in plant-based diet indices and subsequent risk of cancer mortality. Conclusions: Improved plant-based diet quality over a 12-year period was associated with a lower risk of total and CVD mortality, whereas increased consumption of an unhealthful plant-based diet was associated with a higher risk of total and CVD mortality.

Abstract P221: Diet Quality and Incidence of Coronary Heart Disease and Coronary Revascularization Among US Women and Men With Hypertension

Background: Hypertension affects 45% of American adults and is a major risk factor for cardiovascular disease. Regrettably, about less than half of all affected individuals have their hypertension controlled. Healthy dietary patterns have been associated with a lower risk of cardiovascular disease in the general population. However, less is known about this association among individuals with hypertension. Aim: To study four diet quality scores, the alternate Mediterranean Diet (aMED) score; the alternate Healthy Eating Index 2010 (aHEI-2010); the Dietary Approaches to Stop Hypertension (DASH) score; and a Healthful Plant-based Diet Index (hPDI) and the incidence of coronary heart disease (CHD) and coronary revascularization (bypass, angioplasty or stent) among US women and men with hypertension. Methods: We included 22,270 women from the Nurses’ Health Study and 9,846 men from the Health Professionals Follow-up Study that had reported a professionally-diagnosed incident hypertension in 1988 or on subsequent biennial questionnaires. At inclusion, participants were free of other chronic diseases (CHD, coronary artery bypass/angioplasty/stent, angina, other heart disease, stroke, diabetes and cancer). Dietary data were collected every 4 years using a validated semi-quantitative food frequency questionnaire and covariate data were collected biennially. Using the cumulative average of dietary intake after hypertension diagnosis, we calculated hazard ratios (HR, 95% CI) comparing quintiles 5 to 1 of each diet quality score with multivariable Cox proportional hazards regression while adjusting for age, energy intake, alcohol (DASH and hPDI only), margarine (hPDI only), smoking, BMI, physical activity, family history of CHD, lipid-lowering medication, NSAIDs, postmenopausal hormone use (women) and hypertension medication. Results: We documented 922 incident CHD cases (299,520 person-years) and 1845 incident coronary revascularization cases (298,463 person-years) during follow-up. In pooled multivariable analyses, high adherence to all diet quality scores was inversely associated with risk of CHD (aMED: 0.73, 95% CI 0.59-0.91, p trend: &lt;0.01; aHEI-2010: 0.66, 95% CI 0.53-0.82, p trend: &lt;0.0001; DASH: 0.65, 95% CI 0.52-0.83, p trend: &lt;0.0001; hPDI: 0.78, 95% CI 0.61-0.99, p trend: 0.01) and coronary revascularization (aMED: 0.83, 95% CI 0.71-0.96, p trend: 0.02; aHEI-2010: 0.80, 95% CI 0.69-0.94, p trend: &lt;0.001; DASH: 0.88, 95% CI 0.75-1.03, p trend: 0.10; hPDI: 0.81, 95% CI 0.69-0.96, p trend: 0.07). Conclusions: This study suggests that individuals with hypertension may experience a lower risk of CHD and coronary revascularization with high adherence to healthy dietary patterns. Promoting healthy dietary habits among individuals with hypertension could be a cost-efficient and safe way to prevent the incidence of CHD and coronary revascularization.

Postmenopausal hormone use and cutaneous melanoma risk: A French prospective cohort study

Cutaneous melanoma has been suspected to be influenced by female hormones. Several studies reported a positive association between menopausal hormone therapy (MHT) use and melanoma risk; however, previous findings were conflicting. We sought to explore the associations between MHT use and melanoma risk in a prospective cohort of women in France, where a particularly wide variety of MHT formulations are available. E3N is a prospective cohort of 98,995 French women aged 40-65 years in 1990. MHT use was assessed through biennial self-administered questionnaires. We used Cox proportional hazards regression models adjusted for age and skin cancer risk factors. Over 1990-2008, 444 melanoma cases were ascertained among 75,523 postmenopausal women. Ever use of MHT was associated with a higher melanoma risk (hazard ratio (HR) = 1.35, 95% confidence intervals (CI) = 1.07-1.71). The association was strongest among past users (HR = 1.55, CI = 1.17-2.07, homogeneity for past vs. recent use: p = 0.11), and users of MHT containing norpregnane derivatives (HR = 1.59, CI = 1.11-2.27), although with no heterogeneity across types of MHT (p = 0.13). Among MHT users, the association was similar across durations of use. However, a higher risk was observed when treatment onset occurred shortly after menopause (<6 months: HR = 1.55, CI = 1.16-2.07 vs. ≥2 years). Associations between MHT use and melanoma risk were similar after adjustment for UV exposure, although MHT users were more likely to report sunscreen use than nonusers. Our data do not support a strong association between MHT use and melanoma risk. Further investigation is needed to explore potential effect modification by UV exposure on this relationship.

Sex hormone levels and risk of primary open-angle glaucoma in postmenopausal women.

We evaluated the relation of prediagnostic sex hormone levels in postmenopausal women with primary open-angle glaucoma (POAG) and intraocular pressure (IOP). Among postmenopausal participants of the Nurses' Health Study, POAG cases (n = 189; diagnosed 1990-2008) and controls (n = 189) were matched on age, fasting status, and postmenopausal hormone use at blood draw (1989-1990). Plasma concentrations of estrone sulfate, estradiol, testosterone, sex hormone binding globulin, and dehydroepiandrosterone sulfate were assessed. The primary outcome was POAG; in secondary analyses, among cases only, we evaluated maximum untreated IOP at diagnosis. Multivariable-adjusted logistic/multiple linear regression models were used to evaluate tertiles (Ts) of biomarker levels and the two outcomes, adjusting for various potential confounders. We observed no significant associations of estrone, estradiol, sex hormone binding globulin, or dehydroepiandrosterone sulfate with POAG risk or with maximum IOP at glaucoma diagnosis among cases. Suggestive significant associations were observed with highest testosterone and POAG risk (T3 vs T1 multivariable-adjusted odds ratio 1.84; 95% confidence interval 1.02, 3.33; P trend 0.10). Similarly, for maximum IOP at diagnosis among cases only (mean 8 years after blood draw), higher testosterone was significantly associated with higher IOP (multivariable-adjusted difference in IOP T3 vs T1 2.17 mm Hg; 95% confidence interval 0.34, 3.99; P trend 0.02). Overall, plasma sex hormone levels in postmenopausal women were not associated with POAG risk; however, a trend of higher testosterone levels being associated with higher POAG risk and higher IOP at diagnosis was observed and needs confirmation.

Association of Depression With Risk of Incident Systemic Lupus Erythematosus in Women Assessed Across 2 Decades

It has long been hypothesized that depression may increase the risk of developing autoimmune disease; however, rigorous empirical evidence is sparse. To evaluate whether an association exists between depression and risk of incident systemic lupus erythematosus (SLE), a paradigmatic, systemic autoimmune disease. This 20-year prospective, longitudinal cohort study evaluated data collected from 2 cohorts of women participating in the Nurses' Health Study (1996-2012) and the Nurses' Health Study II (1993-2013). Data analyses were conducted from August 2017 to May 2018. Incident SLE with 4 or more American College of Rheumatology criteria was ascertained by self-report and confirmed by medical record review. Depression was assessed repeatedly throughout follow-up according to whether women reported having received a clinician's diagnosis of depression, regular antidepressant use, or a score of less than 60 on the 5-item Mental Health Inventory (MHI-5). Whether longitudinally assessed health risk factors (eg, cigarette smoking, body mass index, oral contraceptive use, menopause or postmenopausal hormone use, alcohol use, exercise, or diet) accounted for increased SLE risk among women with vs without depression was examined. Cox proportional hazards regression models were used to estimate risk of SLE. In addition, the association of depression lagged by 4 years, and depression status at baseline with incident SLE throughout follow-up was assessed. Data from 194 483 women (28-93 years of age; 93% white) were included. During 20 years of follow-up, 145 cases of SLE occurred. Compared with women with no depression, women with a history of depression had a subsequent increased risk of SLE (HR, 2.67; 95% CI, 1.91-3.75; P < .001). Adjustment for body mass index, cigarette smoking, and oral contraception and postmenopausal hormone use slightly attenuated associations (adjusted HR, 2.45; 95% CI, 1.74-3.45; P < .001). The SLE risk was elevated with each of the 3 following depression indicators modeled separately: clinician's diagnosis of depression (HR, 2.19; 95% CI, 1.29-3.71), antidepressant use (HR, 2.80; 95% CI, 1.94-4.05), and MHI-5 scores indicating depressed mood (HR, 1.70; 95% CI, 1.18-2.44). Associations remained strong when depression status was lagged by 4 years with respect to the outcome (HR, 1.99; 95% CI, 1.32-3.00) and when depression status at baseline was used as the exposure (HR, 2.28; 95% CI, 1.54-3.37). This study contributes to increasing evidence that depression may be associated with increased risk of SLE and suggests that the association is not fully explained by measured health factors or behaviors.

Serum metabolomic profiles associated with postmenopausal hormone use.

Postmenopausal hormone use is linked to several health outcomes and the risk associated with some may differ depending on whether estrogen is used alone or in combination with progestin. Metabolomic analyses of postmenopausal hormone use and differences between hormone regimes was done to identify metabolites associated with each type of hormone treatment. Untargeted metabolomics analysis was done on serum from 1336 women enrolled in the Cancer Prevention II Nutrition Cohort. Levels of 781 named metabolites were compared between 667 nonusers with 332 estrogen-only and with 337 estrogen plus progestin users using linear regression. Metabolite levels were also compared between estrogen-only and estrogen plus progestin users. Compared to nonusers, 276 metabolites were statistically significantly (P < 6.40 × 10- 5) associated with estrogen-only use and 222 were associated with estrogen plus progestin use. The metabolites associated with both types of hormones included numerous lipids, acyl carnitines, and amino acids as well as the thyroid hormone thyroxine and the oncometabolite fumarate. The 65 metabolites that differed significantly between estrogen-only and estrogen plus progestin users included 19 steroids and 12 lipids that contained the bioactive fatty acid arachidonic acid. These findings suggest that postmenopausal hormone use influences metabolic pathways linked to a variety of cellular processes, including the regulation of metabolism and stress responses, energy production, and inflammation. The differential association of numerous lipids which influence cellular signaling suggests that differences in signal transduction may contribute to the disparate risks for some diseases between estrogen-only and estrogen plus progestin users.

Abstract 3221: Plasma B-vitamin and one-carbon metabolites and risk of breast cancer before and after folic acid fortification in the US

Abstract Background: Prior epidemiologic findings for plasma folate and B-vitamins and breast cancer risk are inconsistent and have not assessed the possible influence of folic acid fortification mandated in 1998. Excess folate, through the one-carbon cycle, might promote neoplastic lesions through DNA synthesis and methylation and inactivation of tumor suppressor genes. However, deficiencies in folate and other B-vitamins may also stimulate carcinogenesis through this same cycle. With concern for carcinogenesis at both low and high folate levels, folic acid fortification has been controversial. Therefore, we examined the associations between plasma folate, B12, B6, homocysteine, cysteine, and cysteinylglycine and breast cancer risk, before and after fortification. Methods: We conducted a nested case-control study within the prospective Nurses' Health Study. In 1989-1990 (pre-fortification), 32,826 women donated a first blood sample and 18,743 donated an additional blood sample in 2000-2001 (post-fortification). From 1989 to 2006, 1874 incident breast cancer cases with at least one blood sample and 367 with two blood samples were matched 1:1 to controls on age, date/ time of blood draw, fasting status, postmenopausal hormones use, and menopausal status. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) adjusting for age at menarche, parity/age at first birth, age at menopause, family history of breast cancer, history of benign breast disease, height, body mass index at 18, weight change since 18, and alcohol intake. Additionally to assess the effect of fortification, we cross-classified plasma levels at the median for women with two bloods and used unconditional logistic regression adjusting for breast cancer risk factors using low (&amp;lt;median) in both 1990 and 2000 as the referent group. Results: Overall, higher plasma folate, B12, B6, homocysteine, cysteine, and cysteinylglycine levels were not associated with breast cancer risk. For example, comparing women in the highest versus lowest quintile of 1990 plasma folate, adjusted RR (95% CI) was 0.95 (0.77-1.17) for breast cancer. Associations did not vary by in situ /invasive, hormone receptor status, or molecular subtype of the tumor. Additionally, associations did not vary before/after fortification. For example, compared to those with consistently low plasma folate levels, RRs (95% CI) were 0.90 (0.58-1.40) among those that were low 1990/ high 2000, 0.93 (0.59-1.45) among those high 1990/ low 2000, and 1.10 (0.75-1.63) among those that were consistently high. Conclusion: Plasma folate, B12, B6, homocysteine, cysteine, and cysteinylglycine were not significantly associated with breast cancer overall, before and after fortification, or with specific molecular subtypes. These results do not support concerns about folic acid fortification and breast cancer risk. Citation Format: Serena C. Houghton, A. Heather Eliassen, Shumin M. Zhang, Jacob Selhub, Bernard A. Rosner, Walter C. Willett, Susan E. Hankinson. Plasma B-vitamin and one-carbon metabolites and risk of breast cancer before and after folic acid fortification in the US [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3221.

Interactions of alcohol and postmenopausal hormone use in regards to mammographic breast density

We investigated the association of alcohol intake with mammographic breast density in postmenopausal women by their hormone therapy (HT) status. This study included 2,100 cancer-free postmenopausal women within the Nurses' Health Study and Nurses' Health Study II cohorts. Percent breast density (PD), absolute dense (DA), and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root transformed. Alcohol consumption was assessed with a food frequency questionnaire (0, < 5, and ≥ 5g/day). Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to examine associations between alcohol and breast density measures in women with no HT history, current, and past HT users. In multivariable analyses, we found no associations of alcohol consumption with PD (p trend = 0.32) and DA (p trend = 0.53) and an inverse association with NDA (β = - 0.41, 95% CI - 0.73, - 0.09 for ≥ 5g/day, p trend < 0.01). In the stratified analysis by HT status, alcohol was not associated with PD in any of the strata. We found a significant inverse association of alcohol with NDA among past HT users (β = - 0.79, 95% CI - 1.51, - 0.07 for ≥ 5g/day, p trend = 0.02). There were no significant interactions between alcohol and HT in relation to PD, DA, and NDA (p interaction = 0.19, 0.42, and 0.43, respectively). Our findings suggest that associations of alcohol with breast density do not vary by HT status.

Interactions of coffee consumption and postmenopausal hormone use in relation to breast cancer risk in UK Biobank.

We investigated the association of coffee consumption with postmenopausal breast cancer risk, overall and by the status of postmenopausal hormone therapy (PMH). This study included 126,182 postmenopausal women (2,636 with breast cancer and 123,546 without) from UK Biobank. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers. Information on breast cancer risk factors and coffee consumption was collected at baseline and updated during follow-up. We used Cox proportional hazards regression to evaluate associations between coffee consumption and breast cancer, overall and in stratified analyses by woman's PMH status (none, past, current). In the overall analysis, coffee consumption was not associated with breast cancer risk (Hazard Ratio [HR] 1.00, 95% CI 0.91-1.11 for 2-3 cups/day, and HR 0.98, 95% CI 0.87-1.10 for ≥ 4 cups/day, p-trend = 0.69). Women with no PMH history who consumed ≥ 4 cups/day had a 16% reduced risk of breast cancer as compared to women who consumed < 7 cups/week (HR 0.84, 95% CI 0.71-1.00). Among women with past PMH, those consuming ≥ 4 cups/day had a 22% greater risk of breast cancer than women consuming < 7 cups/week (HR 1.22, 95% CI 1.01-1.47). No association was found among current PMH users. We found no significant interaction between PMH and coffee consumption (p = 0.24). Coffee consumption might be associated with increased breast cancer risk in women who used hormones in the past. Further studies are warranted to confirm these findings and elucidate potential biological mechanisms underlying the observed associations.

Sex and ethnic/racial-specific risk factors for gallbladder disease

BackgroundGallbladder disease (GBD) is a highly prevalent condition; however, little is known about potential differences in risk factors by sex and ethnicity/race. Our aim was to evaluate dietary, reproductive and obesity-related factors and GBD in multiethnic populations.MethodsWe performed a prospective analysis from the Multiethnic Cohort study who self-identified as non-Hispanic White (n = 32,103), African American (n = 30,209), Japanese (n = 35,987), Native Hawaiian (n = 6942) and Latino (n = 39,168). GBD cases were identified using Medicare and California hospital discharge files (1993–2012) and self-completed questionnaires. We used exposure information on the baseline questionnaire to identify exposures of interest. Associations were estimated by hazard ratios and 95% confidence intervals using Cox models adjusted for confounders.ResultAfter a median 10.7 years of follow-up, there were 13,437 GBD cases. BMI over 25 kg/m2, diabetes, past and current smoking, red meat consumption, saturated fat and cholesterol were significant risk factors across ethnic/racial populations (p-trends < 0.01). Protective factors included vigorous physical activity, alcohol use, fruits, vegetables and foods rich in dietary fiber (p-trends < 0.01). Carbohydrates were inversely associated with GBD risk only among women and Latinos born in South America/Mexico (p-trend < 0.003). Parity was a significant risk factor among women; post-menopausal hormones use was only associated with an increased risk among White women (estrogen-only: HR = 1.24; 95% CI = 1.07–1.43 and estrogen + progesterone: HR = 1.23; 95% CI = 1.06–1.42).ConclusionOverall, dietary, reproductive and obesity-related factors are strong risk factors for GBD affecting men and women of different ethnicities/races; however some risk factors appear stronger in women and certain ethnic groups.

Differences in Parkinson's Disease Risk with Caffeine Intake and Postmenopausal Hormone Use.

Caffeine intake has been associated with a lower risk of Parkinson's disease (PD). This association is robust in men, but inconsistent in women due to a possible interaction with post-menopausal hormone (PMH) use. To (1) evaluate the association between caffeine intake and PD risk and (2) assess potential effect modification of the association by PMH use among women. We examined associations between caffeine intake and incident PD risk in the Nurses' Health Study (NHS) (N = 121,701 women) and the Health Professionals Follow-up Study (HPFS) (N = 51,529 men). Dietary data on coffee and caffeine from other sources were collected every four years using a validated semi-quantitative food frequency questionnaire for both cohorts. Information on lifestyle and incident PD diagnosis was updated biennially and PD diagnoses were confirmed by medical record review. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models. We documented a total of 1,219 PD cases over the follow-up period. The multivariable-adjusted HR comparing the highest to lowest quintile of caffeine intake was 0.50 (95% CI: 0.37, 0.68; Ptrend<0.0001) in the HPFS. Among women, there was a suggestion of an interaction between coffee intake and PMH use (P = 0.08). In the pooled analyses combining men and women who have never used PMH, the risk of PD was lower as coffee intake increased (Ptrend<0.001). Our results support previous findings that increased caffeine intake may be associated with a decreased PD risk in men and women who have never used PMH.

Real-world evidence in the treatment of ovarian cancer

Introduction‘Real-world evidence (RWE)’ refers to information on the utilization and outcome of new therapies and technologies in clinical practice. RWE may include single institution cohort studies, population-based health services studies, or (inter)national data on survival and mortality. This paper reviews RWE on the impact of treatment in ovarian cancer. Materials and methodsA literature review of publications addressing population level survival outcomes of new surgical and systemic treatment interventions in ovarian cancer was undertaken. In addition, literature and international cancer registry trends in ovarian cancer survival, mortality and incidence rates were compiled. These latter were utilized to make inferences on the relative impact of new treatments as well as changing incidence rates on observed mortality trends. ResultsThe last four decades have seen new systemic and surgical treatments introduced into practice for ovarian cancer based on randomized trial evidence. However, there has been little published on population level uptake and survival outcomes of those interventions. Exceptions were population studies on intraperitoneal chemotherapy and neoadjuvant chemotherapy. One paper demonstrated modest uptake of intraperitoneal chemotherapy and evidence of improved survival. Cancer registry statistics revealed falling incidence rates (∼1%–2% per year) for ovarian cancer across Europe, North America and elsewhere over the last three to four decades. Mortality rates also declined by ∼1%–2% per year over this period. Population 5-year relative survival estimates also improved over this period [from 33.7% in 1975 to 46.2% in 2008 (SEER data)]. ConclusionsThere are few RWE studies of specific treatments in ovarian cancer. Trends in relative survival and population mortality have shown improvements. Mortality changes can be explained in part by reductions in ovarian cancer incidence rates (speculated to be due to use of oral contraceptives and reduction in postmenopausal hormone use). However, it is plausible that at least some of the mortality reduction is related to improved survival of patients with the introduction of effective new treatments.

Plasma Retinol-Binding Protein 4 Levels and the Risk of Ischemic Stroke among Women

Plasma retinol-binding protein 4 (RBP4) levels have been associated with cardiovascular risk factors and risk of coronary heart disease, but little is known about the association between RBP4 and the risk of ischemic stroke. We hypothesized that elevated RBP4 levels would be associated with an increased risk of ischemic stroke among women. We performed a nested case-control study among women enrolled in the Nurses' Health Study who provided blood samples between 1989 and 1990 and were free of prior stroke and cancer. We measured prediagnostic RBP4 levels in 471 ischemic stroke cases who were confirmed by medical record review and in 471 controls who were matched 1:1 to the cases on age, race, blood collection date, menopausal status, postmenopausal hormone use, and smoking status. We analyzed the association between RBP4 levels and ischemic stroke using multivariable conditional logistic regression conditional on the matching factors and adjusted for physical activity, body mass index, aspirin use, alcohol consumption, diet, history of diabetes, high cholesterol, high blood pressure, or heart disease, and cholesterol and hemoglobin A1C levels. Median levels of RBP4 were similar in cases (31.1 µg/mL) and controls (31.0 µg/mL; P value from the Wilcoxon rank-sum test = .82). Quartiles of RBP4 were not associated with an increased risk of ischemic stroke (highest quartile compared to lowest quartile: multivariate-adjusted odds ratio, .75; 95% confidence interval, .48, 1.17). We also did not observe associations between RBP4 and ischemic stroke of thrombotic or embolic origin. Elevated levels of RBP4 were not associated with an increased risk of ischemic stroke.

Relationship between tooth loss and peripheral arterial disease among women.

We assessed the longitudinal association between tooth loss and peripheral arterial disease (PAD) within the Nurses' Health Study. After excluding participants with prior cardiovascular diseases, 277 of 79,663 women were confirmed as PAD cases during 16years of follow-up. Number of teeth and recent tooth loss were reported initially in 1992. Subsequent tooth loss was recorded in 1996 and in 2000. We evaluated the associations of baseline number of teeth and recent tooth loss with risk of PAD, adjusting for age, smoking, diabetes, hypertension, high cholesterol, aspirin use, family history of myocardial infarction, BMI, alcohol consumption, physical activity, postmenopausal hormone use, and use of vitamin E, vitamin D, multivitamin and calcium. Incident tooth loss during follow-up was significantly associated with higher hazard of PAD (HR=1.31 95% CI: 1.00-1.71). However, the association appeared inverse among never smokers. There was no dose-response relationship between baseline number of teeth and PAD. Tooth loss showed a modest association with PAD, but no dose-response relationship was observed.

Abstract 5311: Weight loss over 10 years of adulthood and subsequent risk of breast cancer: a pooled analysis of 11 cohort studies

Abstract Body fatness is an established risk factor for postmenopausal breast cancer, but it is unknown if this risk associated with excess body weight is reversible. We conducted a pooled analysis of 11 prospective studies in the Pooling Project of Prospective Studies of Diet and Cancer. Each study had adult body weight data at three time points, as well as follow-up for subsequent risk of breast cancer after the third weight measure. Weight change was assessed using reported or measured weight at baseline and two follow-up time points, each generally four to six years apart (over a total of ~10 years). Stable weight for each interval was defined as weight within 2kg of the previous weight. The referent group was women with stable weight (within 2kg) at all three time points across the 10-year period. Among 340,055 women, 10,427 breast cancers were diagnosed during follow-up. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) controlling for baseline body mass index (BMI), baseline physical activity, and postmenopausal hormone (PMH) use at the start of breast cancer follow-up, were estimated using proportional hazards regression on an aggregated dataset from all studies. Women who lost weight and kept the weight off, were at a lower risk of breast cancer than women with stable weight over the 10 years: &amp;gt;2.-4.5kg lost between baseline and the first follow-up body weight measure (n=482 cases): HR=0.92, 95% CI: 0.83-1.03; &amp;gt;4.5-9kg lost (n=283 cases): HR=0.86, 95% CI: 0.76-0.98; &amp;gt;9kg lost (n=95 cases): HR =0.81, 95%CI: 0.65-1.00). Women who initially lost weight (&amp;gt;2kg), but then re-gained it had a similar risk of breast cancer to those with stable weight over the same time period. When results were stratified by baseline age and BMI, there was no association between sustained weight loss and breast cancer among women younger than 50 years, nor those with a normal BMI (18.5-25 kg/m2) before weight loss. Among women who were aged 50 or more years and overweight or obese before the weight loss period, we observed a 21% lower risk of breast cancer for sustained weight loss of ≥4.5kg compared to women with stable weight over the same time period (n=245 cases, HR=0.79, 95% CI: 0.68-0.93). This observed association was driven by women who were not taking PMH (n=156, HR=0.71, 95% CI: 0.58-0.86). In this large, pooled prospective analysis of weight loss and breast cancer risk we found that losing 4.5 kg—and keeping it off—may lower breast cancer risk, particularly for women older than 50 who are overweight or obese. The results may provide motivation for women with elevated BMI to lose weight and potentially reduce their risk of breast cancer. Citation Format: Lauren R. Teras, Alpa V. Patel, Molin Wang, Bette J. Caan, Yu Chen, Avonne E. Connor, A. Heather Eliassen, Susan M. Gapstur, Mia M. Gaudet, Jeanine M. Genkinger, Graham G. Giles, I-Min Lee, Roger Milne, Norie Sawada, Howard D. Sesso, Meir Stampfer, Rulla Tamimi, Cynthia A. Thomson, Shoichiro Tsugane, Kala Visvanathan, Anne Zeleniuch-Jacquotte, Walter C. Willett, Stephanie A. Smith-Warner. Weight loss over 10 years of adulthood and subsequent risk of breast cancer: a pooled analysis of 11 cohort studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5311. doi:10.1158/1538-7445.AM2017-5311