Postmenopausal Breast Cancer Risk Research Articles

Number of lifetime menses increases breast cancer occurrence in postmenopausal women at high familial risk

It is increasingly thought that part of human susceptibility to cancer is the result of evolutionary mismatches: our ancestors evolved cancer suppression mechanisms in a world largely different from our modern environments. In that context, it has been shown in cohorts from general Western populations that reproductive traits modulate breast cancer risk. Overall, the more menses women experience, the more at risk they are to develop postmenopausal breast cancer. This points towards an evolutionary mismatch but brings the question whether the reproductive pattern also modulates the breast cancer risk in menopausal women at high familial risk. We thus studied the influence of menses on breast cancer risk in a case–control study of 90 postmenopausal women (including BRCA1/2 and non BRCA1/2) nested within a cohort at high familial risk. We tested the association of the lifetime number of menses and the number of menses before first full-term pregnancy with postmenopausal breast cancer risk using Cox survival models. We showed that the total lifetime number of menses was significantly associated with postmenopausal breast cancer risk and associated with a quicker onset of breast cancer after menopause. Those results align with similar studies lead in general cohorts and suggest that the reproductive pattern modulates the familial risk of developing breast cancer after menopause. Altogether, those results impact how we envision breast cancer prevention and call for more research on how ecological and genetic factors shape breast cancer risk.

Associations between overall, healthful, and unhealthful low-fat dietary patterns and breast cancer risk in a Mediterranean cohort: The SUN project

ObjectivesDietary patterns may have a greater influence on human health than individual foods or nutrients, and they are also of substantial interest in the field of breast cancer prevention. Beyond the adequate balance of macronutrients, evidence indicates that the quality of macronutrient sources may play an important role in health outcomes. We sought to examine the relationship between healthful and unhealthful low-fat dietary patterns in relation to breast cancer. MethodsWe used observational data from a Mediterranean cohort study (the Seguimiento Universidad de Navarra project). We prospectively followed 10 930 middle-aged women initially free of breast cancer during a median follow-up of 12.1 y. We calculated an overall, an unhealthful, and a healthful low-fat diet score, based on a previously validated 136-item food frequency questionnaire and grouped participants into tertiles. Incident breast cancer—overall and stratified by menopausal status—was the primary outcome. It was self-reported by participants and confirmed based on medical reports or consultation of the National Death Index. We used multivariable Cox regression models adjusted for potential confounders. ResultsDuring 123 297 person-years of follow-up, 150 cases of incident breast cancer were confirmed. No significant associations were observed for overall or premenopausal breast cancer. For postmenopausal women, we observed a significant association for moderate adherence to the unhealthful low-fat dietary score and postmenopausal breast cancer (comparing tertile 2 to tertile 1; hazard ratio = 2.18; 95% confidence interval, 1.15–4.13). ConclusionsIn conclusion, no clear associations were observed, although more research is needed to address the association between an unhealthful dietary pattern and postmenopausal breast cancer risk.

Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort.

Nonsteroidal anti-inflammatory agents (NSAID) are associated with modest inconsistent reductions in breast cancer risk in population-based cohorts, whereas two focused studies of patients with benign breast disease (BBD) have found lower risk with NSAID use. Given that BBD includes fibroinflammatory lesions linked to elevated breast cancer risk, we assessed whether NSAID use was associated with lower breast cancer risk among patients with BBD.Participants were postmenopausal women in the Cancer Prevention Study-II (CPS-II), a prospective study of cancer incidence and mortality, who completed follow-up surveys in 1997 with follow-up through June 30, 2015. History of BBD, NSAID use, and covariate data were updated biennially. This analysis included 23,615 patients with BBD and 36,751 patients with non-BBD, including 3,896 incident breast cancers over an average of 12.72 years of follow-up among participants. NSAID use, overall and by formulation, recency, duration, and pills per month was analyzed versus breast cancer risk overall and by BBD status using multivariable-adjusted Cox models; BBD status and NSAID use were modeled as time-dependent exposures.Patients with BBD who reported using NSAIDs experienced lower breast cancer risk (HR, 0.87; 95% CI, 0.78-0.97), with similar effects for estrogen receptor (ER)-positive breast cancers [HR, 0.85; 95% confidence interval (CI), 0.74-0.97] and ER-negative breast cancers (HR, 0.87; 95% CI, 0.59-1.29); among women without BBD, NSAID use was unrelated to risk (HR, 1.02; 95% CI, 0.92-1.13; Pinteraction = 0.04). Associations stratified by age, obesity, menopausal hormone use, and cardiovascular disease were similar.Among patients with BBD, NSAID use appears linked to lower breast cancer risk. Further studies to assess the value of NSAID use among patients with BBD are warranted. We examined whether NSAID use, a modifiable exposure, is associated with breast cancer risk in postmenopausal women from the Cancer Prevention Study-II with self-reported benign breast disease, an often inflammatory condition associated with higher rates of breast cancer.

Breast cancer: Risk factors and prevention strategies

Among the cancer diseases, breast cancer is becoming fast growing leading cause of oncologic mortality among women. It is hoped that, evaluation of different dimensions of breast cancer and its associated factors such as environmental and genetic factors, will increase the efforts of prevention. Current studies suggest that mutations in some genes play an crucial role in susceptibility of breast cancer. Thus, researchers aimed to isolate such breast cancer susceptible genes. Some epidemiologic studied also suggested that, moderate to vigorous exercise for 3-4 hours per week can lower the risk for breast cancer for 30%-40% in women than those of the sedentary women. Obese or overweight women have 50%-250% greater risk for breast cancer after menopause. Alcohol use also increases the risk of both postmenopausal and premenopausal breast cancer. Thus, these trends of sedentary lifestyle, decreasing physical activity and increasing obesity may lead to an increase in the incidence of breast cancer. Thus, adoption of healthy food habits, increasing physical activity and changes in sedentary lifestyle may have a great impact on the prevalence of this disease in future. The treatment strategies for breast cancer are broad-ranging depending on tumor’s biology; stages of the disease; tolerance, and acceptance of the patient. There is various treatment approaches of breast cancer such as radiology, surgery, and systematic therapy (chemotherapy, endocrine therapy and biological therapy) etc. In this article required information about risk factors and current breast cancer prevention strategies are collected through literature review.

Targeting Adiponectin in Breast Cancer.

Obesity and breast cancer are two major health issues that could be categorized as sincere threats to human health. In the last few decades, the relationship between obesity and cancer has been well established and extensively investigated. There is strong evidence that overweight and obesity increase the risk of postmenopausal breast cancer, and adipokines are the central players in this relationship. Produced and secreted predominantly by white adipose tissue, adiponectin is a bioactive molecule that exhibits numerous protective effects and is considered the guardian angel of adipokine. In the obesity-cancer relationship, more and more evidence shows that adiponectin may prevent and protect individuals from developing breast cancer. Recently, several updates have been published on the implication of adiponectin in regulating tumor development, progression, and metastases. In this review, we provide an updated overview of the metabolic signaling linking adiponectin and breast cancer in all its stages. On the other hand, we critically summarize all the available promising candidates that may reactivate these pathways mainly by targeting adiponectin receptors. These molecules could be synthetic small molecules or plant-based proteins. Interestingly, the advances in genomics have made it possible to create peptide sequences that could specifically replace human adiponectin, activate its receptor, and mimic its function. Thus, the obvious anti-cancer activity of adiponectin on breast cancer should be better exploited, and adiponectin must be regarded as a serious biomarker that should be targeted in order to confront this threatening disease.

Magnitude and attributed reasons for adult weight gain amongst women at increased risk of breast cancer

BackgroundExcess weight (BMI ≥25.0 kg/m2) and weight gain during adult life increase the risk of postmenopausal breast cancer in women who are already at increased risk of the disease. Reasons for weight gain in this population can inform strategies for weight gain prevention.MethodsBaseline data from six weight loss studies for women at increased risk of breast cancer (age 31–74 years) were collated. Self-reported patterns of adult weight gain and attributed reasons for weight gain before joining the weight loss study were reported for the whole population and secondary analyses reported the different reasons given by women with/without children, pre−/peri- or postmenopausal, and moderate/high risk of breast cancer.ResultsFive hundred and one women with a mean age of 47.6 (SD 8.4) years and median BMI of 29.9 (IQR 27.0–34.7) kg/m2 were included in the analyses. The median weight gain since young adulthood (18–20 years) was 20.5 (IQR 14.0–29.7) kg or 33.7 (23.4–50.2) % and median annual weight gain was 0.73 (IQR 0.51–1.08) kg. Four hundred and one women were included in analysis of weight gain reasons. The main five self-reported reasons for weight gain were children / childcare / pregnancy (stated by 55.9% of participants), followed by inactivity (41.9%), comfort or boredom eating (38.2%), portion size (32.4%), and stress (27.4%). Reasons appeared broadly similar between the different groups in the secondary analyses.ConclusionsWe have highlighted common reasons for weight gain in women at increased risk of breast cancer. This will inform future interventions to support women to avoid weight gain in adulthood which would reduce the burden of breast cancer.Trial registrationNIHR NRR N0226132725, ISRCTN52913838, ISRCTN77916487, ISRCTN91372184, ISRCTN10803394 and ISRCTN16431108.

Food additive emulsifiers and cancer risk: results from the French prospective NutriNet-Santé cohort

Abstract Background Food additive emulsifiers are found in thousands of industrial foods and may exert deleterious effects on gut microbiota and carcinogenesis according to experimental studies. However, their associations with cancer risk has not been investigated yet. This study aimed to investigate these associations in a large population-based prospective cohort. Methods This study included 102,485 French adults from the NutriNet-Santé cohort (42.1y [14.5], 78.8% female, 2009-2021). Food additive emulsifier intakes were estimated using repeated 24h dietary records linked to brand-specific food composition databases on food additives. Associations with incident cancer risk were assessed using Multivariable Cox models. Results 3,511 incident cancer cases were diagnosed during follow-up (1,026 breast, 431 prostate, and 279 colorectal cancers). Intakes of sodium citrate (E331, HR = 1.12 [1.02-1.23], p-trend=0.009), xanthan gum (E415, HR = 1.11 [1.02-1.21], p-trend=0.02), and mono- and diglycerides of fatty acids (E471, HR = 1.17 [1.06-1.28], p-trend=0.001 and total: E471, E472a-b-c-e, HR = 1.11, [1.02-1.22], p-trend=0.02) were associated with increased overall cancer risk. Higher intakes of E331 (p-trend = 0.046), sodium stearoyl-2-lactylate (E481, p-trend=0.01), total lactylates (E481-482, p-trend=0.01), total celluloses (E460-468, p-trend=0.03), carob bean gum (E410, p-trend=0.01), and E471 (p-trend=0.006) were associated with increased overall breast cancer risk. Higher intakes of carrageenan (E407, p-trend=0.04), E415 (p-trend=0.02), and triphosphates (E451, p-trend=0.03) were associated with increased post-menopausal breast cancer risk. Conclusions These results are the first to investigate and report direct associations between cancer risk and exposures to seven individual and three groups of food additive emulsifiers. If replicated, they may have an important public health impact, considering the omnipresence of these additives in industrial foods globally. Key messages • This study is the first to precisely assess exposures to food additive emulsifiers in a population-based study. • Intakes of food additive emulsifiers were associated with increased risk of cancer.

Postmenopausal overweight and breast cancer risk; results from the KARMA cohort

PurposeTo study the risk of incident breast cancer and subtype-specific breast cancer in relation to excess body weight in a contemporary Swedish prospective cohort study, The Karolinska Mammography Project for Risk Prediction of Breast Cancer, KARMA.MethodsA total of 35,412 postmenopausal women attending mammography and included in the KARMA study provided baseline data on body mass index (BMI) and potential confounders. During eight years of follow-up, 822 incident invasive breast cancer cases were identified.ResultsWomen with overweight (BMI ≥ 25–< 30 kg/m2) constituting 34% of the study cohort had an increased risk of incident breast cancer with an adjusted Hazard Ratio (HRadj) 1.19 (95% CI 1.01–1.4). A similar, however, non-significant, association was found for women with obesity (BMI ≥ 30 kg/m2) conferring 13% of the cohort, with a HRadj of 1.19 (95% CI 0.94–1.5). Overweight was associated with risk of node-negative disease (HRadj 1.29, 95% CI 1.06–1.58), whereas obesity was associated with node-positive disease (HRadj 1.64, 95% CI 1.09–2.48). Both overweight and obesity were associated with risk of estrogen receptor positive (ER+) disease (HRadj 1.20, 95% CI 1.00–1.44 and HRadj 1.33, 95% CI 1.03–1.71, respectively), and low-grade tumors (HRadj 1.25, 95% CI 1.02–1.54, and HRadj 1.40, 95% CI 1.05–1.86, respectively). Finally, obesity was associated with ER+HER2 negative disease (HRadj 1.37, 95% CI 1.05–1.78) and similarly luminal A tumors (HRadj 1.43, 95% CI 1.02–2.01).ConclusionOverweight and obesity are associated with an increased risk of developing breast cancer, specifically ER+, low-grade, and for obesity, node-positive, high-risk breast cancer indicating a further need for risk communication and preventive programs.

Menopausal hormone-replacement therapy and breast cancer risk: An updated and simplified view

Menopause, the menstrual cessation due to accelerated decline in ovarian function along with changes in the hormonal milieu, marks the end of reproductive fertility in women. This phenomenon is accompanied by various physiological and psychological symptoms, generally managed, and/or alleviated by menopausal hormone therapy (MHT). An association between MHT and the risk of developing breast cancer (BC), although controversial, is known for quite some time, particularly among combined MHT users. The risk varies with the time and type of MHT usage and persists after decades of treatment. The purpose of this review is to present an updated version of MHT and its association with postmenopausal BC risk.

Air pollution and green spaces in relation to breast cancer risk among pre and postmenopausal women: A mega cohort from Catalonia

BackgroundThe association between air pollution and green spaces with breast cancer risk stratified by menopausal status has not been frequently investigated despite its importance given the different impact of risk factors on breast cancer risk depending on menopausal status. ObjectivesTo study the association between air pollution, green spaces and pre and postmenopausal breast cancer risk. MethodsWe conducted a population-based cohort study using electronic primary care records in Catalonia. We included women aged 17–85 years free of cancer at study entry between 2009 and 2017. Our exposures were particulate matter <2.5 μm (PM2.5) & <10 μm (PM10), nitrogen dioxide (NO2), normalized difference vegetation index (NDVI), and percentage of green spaces estimated at the census tract level. Breast cancer was identified with ICD-10 code C50. We estimated cause-specific hazard ratios (HR) for the relationship between each individual exposure and pre and postmenopausal breast cancer risk, using linear and non-linear models. ResultsOf the 1,054,180 pre and 744,658 postmenopausal women followed for a median of 10 years, 6,126 and 17,858 developed breast cancer, respectively. Among premenopausal women, only very high levels of PM10 (≥46 μg/m3) were associated with increased cancer risk (compared to lower levels) in non-linear models. Among postmenopausal women, an interquartile range increase in PM2.5 (HR:1.03; 95%CI:1.01–1.04), PM10 (1.03; 1.01–1.05), and NO2 (1.05; 1.02–1.08) were associated with higher cancer risk. NDVI was negatively associated with decreased cancer risk only among postmenopausal women who did not change residence during follow-up (0.84; 0.71–0.99) or who were followed for at least three years (0.82; 0.69–0.98). DiscussionLiving in areas with high concentrations of PM2.5, PM10, and NO2 increases breast cancer risk in postmenopausal women while long-term exposure to green spaces may decrease this risk. Only very high concentrations of PM10 increase breast cancer risk in premenopausal women.

Dietary intake of branched-chain amino acids in relation to the risk of breast cancer.

Given that, studies on the association of dietary intake of branched-chain amino acids (BCAAs) with risk of cancers, especially breast cancer, are limited, we aimed to examine the association between dietary intake of BCAAs and risk of breast cancer. This case-control study was performed on Iranian women aged ≥ 30years from July 2013 to July 2015. Overall 1050 women including 350 patients and 700 controls were included. Breast cancer was diagnosed by physical examination, mammography and pathological confirmation. We assessed dietary intakes using the validated 106-item Willett-format semi-quantitative dish-based food frequency questionnaire. The total intake of valine, leucine, and isoleucine from all food items in the questionnaire was used to calculate BCAAs intake. To estimate odds ratios (ORs) and 95% confidence intervals (95% CI), we used logistic regression analysis. After controlling for potential confounders, we found that women in the highest quartile of BCAAs had lower odds of breast cancer compared with the first quartile (OR: 0.50; 95% CI 0.34-0.72). When we stratified the analysis based on menopausal status, a significant inverse association between BCAAs intake and odds of postmenopausal breast cancer was observed (OR: 0.22; 95% CI 0.13-0.39), although this significant relationship was not found in premenopausal breast cancer (OR: 2.57; 95% CI 0.51-12.73). Also, this significant association was also observed for valine, leucine, and isoleucine separately. We found that higher dietary intake of BCAAs was significantly associated with a reduced risk of postmenopausal breast cancer.

Body Mass Index Is Inversely Associated with Risk of Postmenopausal Interval Breast Cancer: Results from the Women's Health Initiative.

Simple SummaryBreast cancer diagnosed between a negative screening mammogram and the next regularly scheduled mammographic exam is called interval breast cancer. It is often diagnosed at more advanced stages than screening-detected cancers. While body mass index (BMI) is a risk factor for postmenopausal breast cancer overall and can influence the accuracy of mammography, the association of BMI with postmenopausal interval breast cancer is unclear. Using data from the Women’s Health Initiative, a national study among postmenopausal women, we found that lower BMI was significantly associated with a higher risk of interval breast cancers diagnosed within 1 year of a negative mammogram after adjustment for multiple risk factors. These findings suggest that obesity is associated with a lower risk of postmenopausal interval breast cancer. Future research using body composition measures is warranted to confirm our findings.Interval breast cancer refers to cancer diagnosed after a negative screening mammogram and before the next scheduled screening mammogram. Interval breast cancer has worse prognosis than screening-detected cancer. Body mass index (BMI) influences the accuracy of mammography and overall postmenopausal breast cancer risk, yet how is obesity associated with postmenopausal interval breast cancer incidence is unclear. The current study included cancer-free postmenopausal women aged 50–79 years at enrollment in the Women’s Health Initiative who were diagnosed with breast cancer during follow-up. Analyses include 324 interval breast cancer cases diagnosed within one year after the participant’s last negative screening mammogram and 1969 screening-detected breast cancer patients. Obesity (BMI ≥ 30 kg/m2) was measured at baseline. Associations between obesity and incidence of interval cancer were determined by sequential logistic regression analyses. In multivariable-adjusted models, obesity was inversely associated with interval breast cancer risk [OR (95% CI) = 0.65 (0.46, 0.92)]. The inverse association persisted after excluding women diagnosed within 2 years [OR (95% CI) = 0.60 (0.42, 0.87)] or 4 years [OR (95% CI) = 0.56 (0.37, 0.86)] of enrollment, suggesting consistency of the association regardless of screening practices prior to trial entry. These findings warrant confirmation in studies with body composition measures.

A metabolomic analysis of adiposity measures and pre- and postmenopausal breast cancer risk in the Nurses' Health Studies.

Adiposity is consistently positively associated with postmenopausal breast cancer and inversely associated with premenopausal breast cancer risk, though the reasons for this difference remain unclear. In this nested case-control study of 1649 breast cancer cases and 1649 matched controls from the Nurses' Health Study (NHS) and the NHSII, we selected lipid and polar metabolites correlated with BMI, waist circumference, weight change since age 18, or derived fat mass, and developed a metabolomic score for each measure using LASSO regression. Logistic regression was used to investigate the association between this score and breast cancer risk, adjusted for risk factors and stratified by menopausal status at blood draw and diagnosis. Metabolite scores developed among only premenopausal or postmenopausal women were highly correlated with scores developed in all women (r = 0.93-0.96). Higher metabolomic adiposity scores were generally inversely related to breast cancer risk among premenopausal women. Among postmenopausal women, significant positive trends with risk were observed (e.g., metabolomic waist circumference score OR Q4 vs. Q1 = 1.47, 95% CI = 1.03-2.08, P-trend = 0.01). Though the same metabolites represented adiposity in pre- and postmenopausal women, breast cancer risk associations differed suggesting that metabolic dysregulation may have a differential association with pre- vs. postmenopausal breast cancer.

Association of Obesity and Diabetes With the Incidence of Breast Cancer in Louisiana

Breast cancer is a heterogeneous disease, consisting of multiple molecular subtypes. Obesity has been associated with an increased risk for postmenopausal breast cancer, but few studies have examined breast cancer subtypes separately. Obesity is often complicated by type 2 diabetes, but the possible association of diabetes with specific breast cancer subtypes remains poorly understood. In this retrospective case-control study, Louisiana Tumor Registry records of primary invasive breast cancer diagnosed in 2010-2015 were linked to electronic health records in the Louisiana Public Health Institute's Research Action for Health Network. Controls were selected from Research Action for Health Network and matched to cases by age and race. Conditional logistic regression was used to identify metabolic risk factors. Data analysis was conducted in 2020‒2021. There was a significant association between diabetes and breast cancer for Luminal A, Triple-Negative Breast Cancer, and human epidermal growth factor 2‒positive subtypes. In multiple logistic regression, including both obesity status and diabetes as independent risk factors, Luminal A breast cancer was also associated with overweight status. Diabetes was associated with increased risk for Luminal A and Triple-Negative Breast Cancer in subgroup analyses, including women aged ≥50 years, Black women, and White women. Although research has identified obesity and diabetes as risk factors for breast cancer, these results underscore that comorbid risk is complex and may differ by molecular subtype. There was a significant association between diabetes and the incidence of Luminal A, Triple-Negative Breast Cancer, and human epidermal growth factor 2‒positive breast cancer in Louisiana.

Abstract 2249: A metabolomic analysis of adiposity measures and pre- and postmenopausal breast cancer risk in the Nurses’ Health Studies

Abstract Adiposity is consistently positively associated with postmenopausal breast cancer and inversely associated with premenopausal breast cancer risk. In this nested case-control study of 1651 breast cancer cases and 1651 matched controls from the Nurses’ Health Study (NHS) and the Nurses’ Health Study II (NHSII), we selected lipids and polar metabolites correlated with BMI, waist circumference, weight change since age 18, or derived fat mass, developed a metabolomic score for each measure using LASSO regression, and used logistic regression to investigate the association between this score and breast cancer risk adjusted for risk factors. Analyses were stratified by menopausal status at blood draw and diagnosis. We further explored risk of ER+ and ER- breast cancer.Metabolite correlations were similar across adiposity measures. Metabolite scores developed among only premenopausal or postmenopausal women were highly correlated with scores developed in all women (r=0.94-0.96). Higher metabolomic adiposity scores were generally inversely related to breast cancer risk among premenopausal women. Among postmenopausal women, significant positive trends with risk were observed for higher metabolomic adiposity scores (e.g., metabolomic waist circumference score OR Q4 v. Q1=1.55, 95% CI=1.08-2.22, p-trend=0.01). Metabolites associated with adiposity and breast cancer risk, glycerophosphocholines and branched-chain amino acids, are also associated with metabolic dysregulation. The same metabolites represented adiposity in pre- and postmenopausal women, though breast cancer risk associations still differed by menopausal status. Thus, metabolic dysregulation may have a differential association with pre- vs. postmenopausal breast cancer. Investigation of these metabolites and their role in adiposity-related breast cancer risk should be further explored. Citation Format: Kristen D. Brantley, Oana A. Zeleznik, Barbra A. Dickerman, Raji Balasubramanian, Clary B. Clish, Julian Avila-Pacheco, Bernard Rosner, Rulla M. Tamimi, A. Heather Eliassen. A metabolomic analysis of adiposity measures and pre- and postmenopausal breast cancer risk in the Nurses’ Health Studies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2249.

Risk of Cancer in Regular and Low Meat-Eaters, Fish-Eaters, and Vegetarians: A Prospective Analysis of UK Biobank Participants

ObjectivesVegetarians may have a lower risk of cancer overall; however, for specific cancer sites, the evidence is limited. We aimed to assess the associations of vegetarian and non-vegetarian diets with risks of all cancer, colorectal cancer, postmenopausal breast cancer, and prostate cancer, and to explore the role of potential mediators. MethodsWe conducted a prospective analysis of 472,377 UK Biobank participants who were free from cancer at recruitment. Participants were categorised into regular meat-eaters (n = 247,571), low meat-eaters (n = 205,385), fish-eaters (n = 10,696), and vegetarians (n = 8,685) based on dietary questions completed at recruitment. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all cancer incidence and separate cancer sites across diet groups. ResultsAfter an average follow-up of 11.4 years, 54,961 incident cancers were identified from health records, including 5,882 colorectal, 7,537 postmenopausal breast, and 9,501 prostate cancers. Compared with regular meat-eaters, being a low meat-eater, fish-eater, or vegetarian were all associated with a lower risk of all cancer (HR:0.98, 95% CI:0.96–1.00; 0.90, 0.84–0.96; 0.86, 0.80–0.93, respectively). Being a low meat-eater was associated with a lower risk of colorectal cancer in comparison to regular meat-eaters (0.91, 0.86–0.96). Vegetarian postmenopausal women had a lower risk of breast cancer (0.82, 0.68–0.99), which was attenuated and non-significant after adjusting for BMI (0.87, 0.72–1.05); in mediation analyses, BMI was found to possibly mediate the observed association. In men, being a fish-eater or a vegetarian was associated with a lower risk of prostate cancer (0.80, 0.65–0.99 and 0.69, 0.54–0.89, respectively). ConclusionsThe lower risk of colorectal cancer in low meat-eaters is consistent with previous evidence suggesting an adverse impact of higher meat intake. The lower risk of postmenopausal breast cancer in vegetarian women may be explained by their lower BMI. It is unclear if the other differences observed for all cancers and for prostate cancer reflect causal relationships or are due to residual confounding or differences in cancer detection. Funding SourcesCRUK grant (C8221/A29017) and World Cancer Research Fund UK(2019/1953).

Associations of coffee/caffeine consumption with postmenopausal breast cancer risk and their interactions with postmenopausal hormone use.

We investigated the association of coffee and caffeine with breast cancer (BCa) risk, overall and by ER/PR status. We also examined potential interactions of coffee and caffeine with postmenopausal hormone use. Our study included 77,688 postmenopausal participants from the Women's Health Initiative observational study cohort without a history of any cancer at baseline (except non-melanoma skin) and with valid Food Frequency Questionnaire data and complete data on dietary caffeine. Regular coffee (none, 1, 2-3, 4-5, and ≥ 6 cups/day) and caffeine (tertiles) were assessed at baseline. Information on BCa risk factors was collected at baseline. The associations were examined using survival analysis, accounting for death as a competing risk. The median follow-up time for our cohort was 18.3years. During the follow-up, 5005 women developed invasive breast cancer. In multivariable analysis, coffee was not associated with the overall invasive BCa risk. Higher caffeine intake was mildly associated with increased BCa risk (2nd vs. 1st tertile SHR = 1.10, 95% CI 1.03-1.18, 3rd vs. 1st tertile SHR-1.05, 95% CI 0.98-1.13, overall p = 0.03). We found no interaction of coffee/caffeine with postmenopausal hormone use (p interaction = 0.44 and 0.42, respectively). In the exploratory analysis by ER/PR status, we found a positive association of caffeine with ER+ /PR+ BCa (2nd vs. 1st tertile SHR = 1.17, 95% CI 1.07-1.28, 3rd vs. 1st tertile SHR = 1.13, 95% CI 1.03-1.24, overall p = 0.002); no associations were observed for ER-/PR- tumors. Coffee was not associated with the risk of ER+ /PR+ or ER-/PR- tumors. We found no associations of coffee with BCa risk, overall and for ER/PR-defined tumor subtypes. The higher caffeine consumption was mildly and positively associated with the overall BCa risk and with ER+ /PR+ tumors.

Bone mineral density and risk of breast cancer: A cohort study and Mendelian randomization analysis.

Estrogen is involved in both bone metabolism and breast cancer proliferation. However, evidence about the risk of breast cancer according to women's bone mineral density (BMD) is scarce, and little is known about their causal associations. Women participating in the UK Biobank cohort were used to investigate the association between BMD and the risk of breast cancer using Cox regression models. Instrumental variants associated with estimated BMD (eBMD) were extracted from genome-wide association studies with European ancestry. Logistic regression was used to calculate the genetic association with breast cancer in the UK Biobank and 2-sample Mendelian randomization (MR) analyses to assess their causal associations with breast cancer. Finally, the pleiotropic conditional false discovery rate (cFDR) method was conducted to further detect common genetic variants between BMD and breast cancer. Compared with the general population, postmenopausal women with BMD T scores <-2.5 had a lower risk of breast cancer (hazard ratio [HR], 0.77; 95% CI, 0.59-1.00), and this effect was stronger in women with fracture (HR, 0.31; 95% CI, 0.12-0.82). In MR analysis, no causal associations between eBMD and breast cancer were observed. The cFDR method identified 63 pleiotropic loci associated with both BMD and breast cancer, of which CCDC170, ESR1, and FTO might play crucial roles in their pleiotropy. An association between BMD and the risk of postmenopausal breast cancer in the UK Biobank was observed, whereas no evidence supported their causal association. Instead, their association could be explained by pleiotropic genetic variants leading to the pathology of osteoporosis and breast cancer.

Anthropometric measures and breast cancer risk among Hispanic women in Puerto Rico.

Increased risk of postmenopausal breast cancer associated with anthropometric measures including Body Mass Index (BMI), adult weight gain, and waist circumference has been observed in North American and European populations, but little evidence is available for Hispanic women. Breast cancer is the leading type of cancer, and leading cause of cancer-related deaths among Hispanic women in Puerto Rico (PR). However, compared with the United States, breast cancer incidence rates are lower but increasing more rapidly. To examine associations between anthropometric characteristics and breast cancer risk in Hispanic women in PR. Data from a population-based case-control study in the San Juan metropolitan region (cases = 315; controls = 348) were used to examine associations between anthropometric measures and breast cancer risk, also considering menopausal status and hormone therapy (HT). Among premenopausal participants, there was a significant trend for lower odds of breast cancer with higher BMI and borderline significant with higher waist to height ratio (WHtR). For postmenopausal participants, a significant trend for lower odds of breast cancer was observed with higher WHtR, and waist to hip ratio (WHR), borderline significant with higher BMI, and higher odds with height. Among postmenopausal participants using HT, a significant trend for lower odds of breast cancer was observed with higher waist circumference, WHtR, WHR, and body shape index. Our study provides evidence of anthropometric differences in relation to breast cancer risk in PR compared to previous studies. Future studies should include analyses of fat and lean mass distribution, and hormone receptor status to further understand anthropometry and breast cancer risk among Hispanic women.

Adherence to the Vegetable-Fruit-Soy Dietary Pattern, a Reference From Mediterranean Diet, Protects Against Postmenopausal Breast Cancer Among Chinese Women.

BackgroundThe diet-center hypothesis has gained much support from the apparent protective effect of the Mediterranean diet on breast cancer. However, the evidence of the association between Mediterranean diet adherence and breast cancer molecular subtypes remains small, especially in non-Mediterranean populations.MethodsThe subjects from the Chinese Wuxi Exposure and Breast Cancer Study, a population-based case-control study, included 818 patients and 935 healthy controls. A validated food frequency questionnaire used for diet assessment and a modified version of the alternate Mediterranean Diet Score, which is called the alternate Chinese Diet Score, was developed to assess adherence to a migrated Chinese version of the Mediterranean diet, which we called the vegetable-fruit-soy dietary pattern. Soy foods, rapeseed oil, and coarse cereals replaced legumes, olive oil, and whole grains reflecting the cuisine of the region. We examined the association between the vegetable-fruit-soy diet adherence and breast cancer risk, stratified by menopause status (pre- or postmenopausal) and receptor status [estrogen-receptor (ER), progesterone-receptor (PR) status, and human epidermal growth factor 2 (HER2)] oncogene expression, followed by five specific combinations (ER+, ER–, ER+/PR+,ER–/PR–, and ER–/PR–/HER2–).ResultsThe results suggest that the vegetable-fruit-soy dietary pattern was inversely associated with postmenopausal breast cancer risk [4th vs. 1st quartile, odds ratio (OR) = 0.57, 95%CI = 0.41, 0.80; P trend < 0.001] and that the inverse association was somewhat stronger to detect among ER- subtypes (OR = 0.63; 95%CI = 0.37, 0.94; P trend = 0.003) and ER–/PR–subtypes (OR = 0.64; 95%CI = 0.41, 0.93; P trend = 0.012). We did not observe any significant association between the vegetable-fruit-soy diet characteristics and ER+ subtype, as well as between PR+ and ER+/PR+ subtypes.ConclusionThe favorable influence from the Mediterranean diet may also apply to Chinese women. The vegetable-fruit-soy dietary pattern may reduce the risk of postmenopausal breast cancer, particularly among ER- subtype, and ER–/PR–subtype.