Risk Of Cancer In Postmenopausal Women Research Articles

Relationship between menopausal hormone therapy and colorectal cancer: a cohort study utilizing the health insurance database in South Korea (HISK)-II.

Many studies have demonstrated that menopausal hormone therapy is associated with a reduced risk for colorectal cancer. This study investigated the relationship between specific hormone therapy regimens and colorectal cancer risk in postmenopausal women in South Korea using national insurance claims data. This population-based, retrospective cohort study used insurance data provided by the Health Insurance Review and Assessment Service between 2007 and 2020. The hormone therapy group comprised women ≥40 years of age who underwent hormone therapy for the first time between 2011 and 2014. The control group included women ≥40 years of age who visited medical institutions for menopause-related issues during the same period but did not undergo hormone therapy. After 1:1 propensity score matching, 153,736 women were grouped into either the hormone therapy or nonhormone therapy groups. The incidence of colorectal cancer was 46 and 53 per 100,000 person-years in the nonhormone therapy and hormone therapy groups, respectively. Hormone therapy was associated with an increased risk for colorectal cancer (hazard ratio 1.124 [95% confidence interval 1.002-1.261]). Subgroup analysis, according to hormone therapy type, revealed no significant differences in the risk of colorectal cancer for estrogen plus progestogen or estrogen therapy alone; however, tibolone was associated with an increased risk of colorectal cancer compared to nonhormone therapy (hazard ratio, 1.178 [95% confidence interval, 1.021-1.359]). This study found an increased risk of colorectal cancer in women receiving hormone therapy, and tibolone was significantly associated with an increased risk of colorectal cancer. However, the magnitude of the increase was small and unlikely to be of clinical significance.

The interrelationship between obesity and race in breast cancer prognosis: a prospective cohort study

BackgroundObesity is associated with an increased breast cancer risk in postmenopausal women and may contribute to worse outcomes. Black women experience higher obesity and breast cancer mortality rates than non-Black women. We examined associations between race, obesity, and clinical tumor stage with breast cancer prognosis.MethodsWe conducted a prospective cohort study in 1,110 breast cancer patients, using univariable and multivariable Cox regression analyses to evaluate the effects of obesity, race/ethnicity, and clinical tumor stage on progression-free and overall survival (PFS and OS).Results22% of participants were Black, 64% were Hispanic White, and 14% were non-Hispanic White or another race. 39% of participants were obese (body mass index [BMI] ≥ 30 kg/m2). In univariable analyses, tumor stage III-IV was associated with worse PFS and OS compared to tumor stage 0-II (hazard ratio [HR] = 4.68, 95% confidence interval [CI] = 3.52–6.22 for PFS and HR = 5.92, 95% CI = 4.00-8.77 for OS). Multivariable analysis revealed an association between Black race and worse PFS in obese (HR = 2.19, 95% CI = 1.06–4.51) and non-obese (HR = 2.11, 95% CI = 1.05–4.21) women with tumors staged 0-II. Obesity alone was not associated with worse PFS or OS.ConclusionsResults suggest a complex interrelationship between obesity and race in breast cancer prognosis. The association between the Black race and worse PFS in tumor stages 0-II underscores the importance of early intervention in this group. Future studies are warranted to evaluate whether alternative measures of body composition and biomarkers are better prognostic indicators than BMI among Black breast cancer survivors.

Multi-Trait Body Shape Phenotypes and Breast Cancer Risk in Postmenopausal Women: A Causal Mediation Analysis in the UK Biobank Cohort

Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers. The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio (WHR). The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions. After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was positively mediated by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 11.4% (95% confidence intervals: 5.1 to 17.8%) and -12.2% (-20.5% to -4.0%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8% (0.6 to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1% (-10.9% to -1.3%)). Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of a generally obese body shape and BC risk, while IGF-1 and SHBG may mediate a tall/lean body shape-BC risk association.

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.

Mildly elevated diastolic blood pressure increases subsequent risk of breast cancer in postmenopausal women in the Health Examinees-Gem study.

Epidemiological evidence suggests that hypertension is associated with breast cancer risk. However, previous studies disregard blood pressure components in the healthy population. We aimed to examine the relationship between systolic and diastolic blood pressure and breast cancer risk in a Korean population-based prospective cohort. A total of 73,031 women from the Health Examinees Gem Study were followed from baseline (2004 to 2013) through 2018. Systolic and diastolic blood pressure were measured by trainee physicians at baseline recruitment and then categorized based on the international guidelines for clinical hypertension. Associations between systolic and diastolic blood pressure with overall breast cancer and stratified by premenopausal and postmenopausal status were evaluated using adjusted multivariable Cox proportional hazard regression. A total of 858 breast cancer cases were recorded for a median follow-up period of 9 years. Compared with the normal DBP category (< 85 mmHg), the normal-high category was positively associated with breast cancer risk in postmenopausal women (85–89 mmHg, HR 1.73 95% CI 1.28–2.33), but not in premenopausal women (85–89 mmHg, HR 0.87 95% CI 0.56–1.35). Similar results were found when all cases of self-reported hypertension were excluded. Results for SBP did not show a significant association with breast cancer risk. The association between DBP and breast cancer suggests DBP could be an important factor in cancer prevention, especially for women after menopause. Our study provides a first detailed approach to understanding the importance of diastolic blood pressure for breast cancer prevention and warrants further investigation.

Dietary selenium intake and thyroid cancer risk in postmenopausal women

ObjectiveIt has been suggested that higher selenium intake and consumption of supplements protect against several cancers. To our knowledge, epidemiologic evidence is rare and inconsistent on the association of selenium level and the risk for thyroid cancer. Therefore, the aim of this study was to examine the association between selenium intake and thyroid cancer risk in postmenopausal women using the Women's Health Initiative (WHI) database. MethodsThe WHI recruited 161 808 postmenopausal women 50 to 79 y of age between September 1, 1993 and December 31, 1998. The present study included 147 348 women 63.15 y of age (SD = 7.21) at baseline. The main exposure was baseline total selenium intake including dietary selenium measured by food frequency questionnaire (FFQ) and supplemental selenium. The outcome was thyroid cancer, which was adjudicated by trained physicians. Cox proportional hazard models were used to analyze the association. ResultsDuring a mean follow-up of 16.4 y until September 30, 2020, 442 thyroid cancer cases were identified. There was no significant association between total selenium intake and thyroid cancer risk after adjusting for multiple covariates (highest versus lowest quartile: hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.60–1.29). Association between total selenium intake and the risk for papillary thyroid cancer was also not significant (highest versus lowest quartile: HR, 1.02; 95% CI, 0.66–1.52). ConclusionsThe present data did not support that either total or dietary selenium intake was associated with the risk for thyroid cancer or the papillary subtype in postmenopausal women ages 50 to 79 y in the United States.

190 Lack of association between dietary and supplemental vitamin E intake with skin cancer risk in postmenopausal women

Risk factors for cutaneous melanoma (CM) and nonmelanoma skin cancer (NMSC) include fair skin and extensive sun exposure. But, incidence has risen despite efforts to promote sun protection. Thus, identifying methods for therapeutic prevention is needed. Antioxidants such as vitamin E are theorized to reduce cancer risk by scavenging reactive species to reduce oxidative stress and DNA damage, but associations between vitamin E intake and skin cancer risk in women remain unclear. To investigate this, we used data from >93,000 postmenopausal women from the observational arm of the Women’s Health Initiative (WHI).

196 Associations between dietary and supplemental vitamin A and skin cancer risk in postmenopausal women

Nonmelanoma skin cancer (NMSC) and cutaneous melanoma (CM) are among the most common cancers in older women. While studies on the protective effects of vitamin A against NMSC have been mixed, a 2012 cohort study which included 36,096 women showed that supplementation with retinol—a form of vitamin A—correlated with reduced CM risk in women. To investigate associations of vitamin A and skin cancer in postmenopausal women, we used data from the Women’s Health Initiative (WHI) observational study of 93,676 postmenopausal women.

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.

Role of oxidative stress in angiogenesis and the therapeutic potential of antioxidants in breast cancer.

The escalation of cancer cases globally, especially breast cancer, is of concern. Angiogenesis is hallmark of cancer pathogenesis and plays an important role in cancer progression and metastasis. Pro-angiogenic agents, secreted by tumor cells, form new blood vessels, and produce reactive oxygen species (ROS). ROS promote angiogenesis via two major pathways: namely Vascular Endothelial Growth Factor (VEGF) dependent and non-VEGF dependent pathways. As a consequence of unbalanced ROS overproduction and low antioxidants levels, oxidative stress occurs and promotes angiogenesis in breast cancer tissues. Thus, the potential use of antioxidants as a preventive therapy in breast cancer. Preclinical studies depict that vitamins A and E may counter oxidative stress resulting in reduction of metastasis and viability of breast cancer. Furthermore, clinical studies demonstrate a decline in breast cancer risk in postmenopausal women upon the consumption of antioxidants. Herein, we discuss various pro-angiogenic agents that may play an important role in breast cancer angiogenesis. Moreover, the contribution of oxidative stress in inducing the angiogenic process is extensively reviewed here. Furthermore, the findings of pre-clinical and clinical studies on the use of antioxidants, namely vitamins A and E, in breast cancer are deliberated upon, along with the role of angiogenesis in cancer therapy.

Abstract 732: Weight gain after age 18 and breast cancer risk: A meta-analysis

Abstract Introduction: Current cancer research recognizes that early life factors are important risk factors for breast cancer. Studies suggest that weight gain after age 18 plays a role in the development of breast cancer; however, the research related to their association is inconsistent. Thus, we performed a meta-analysis to evaluate the associations between weight gain after age 18 and risk of breast cancer and to clarify whether there is heterogeneity stratified by menopausal status. Methods: We performed a comprehensive literature search of all relevant studies published prior to February 19, 2021, according to the established inclusion criteria, utilizing Medline (Ovid), Embase, Scopus, Cochrane Library, and ClinicalTrials.gov. Two reviewers independently reviewed the articles for final inclusion. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies. Summary risk estimates (REs) with the corresponding 95% confidence intervals (CIs) were calculated using a random-effect or fixed-effect model, based on heterogeneity significance. Subgroup analyses were performed based on types of study design (case-control vs. cohort), country of study (the USA vs. other countries), and menopausal status (premenopausal vs. postmenopausal). We conducted sensitivity analysis and publication bias detection. We performed all statistical analyses with STATA version 16.1, and all P values were two-tailed, the test level was 0.05. Results: Seventeen out of 4,368 unique studies (12 case-control studies and 5 cohort studies) met the selection criteria. All studies were considered moderate to high quality with NOS scores that ranged from 5 to 8. Overall, weight gain after age 18 was associated with an increased risk of breast cancer (RE = 1.27; 95%CI = 1.13 - 1.42). In subgroup analyses, menopausal status was a source of heterogeneity. Weight gain after age 18 was associated with an increased risk of breast cancer among postmenopausal women (RE = 1.45; 95% CI = 1.31 - 1.62), but not among premenopausal women (RE = 1.03; 95% CI = 0.95 - 1.11). We did not find differences in associations by type of study design (case-control study: RE = 1.28; 95%CI = 1.09 - 1.51; cohort study: RE = 1.24; 95%CI = 1.07 - 1.44) nor country of study (the USA: RE = 1.28; 95%CI = 1.13 - 1.45; other countries: RE = 1.25; 95%CI = 0.94 - 1.66). The sensitivity analysis confirmed the stability of the results. The funnel plot suggested no publication bias. Conclusion: The current meta-analysis demonstrates that weight gain after age 18 is associated with increased breast cancer risk in postmenopausal women but not in premenopausal women. These findings suggest that it is important to keep weight within the healthy range and manage weight gain in adult life to fight against breast cancer among postmenopausal women. Citation Format: Yunan Han, Ebunoluwa E. Otegbeye, Carrie Stoll, Angela Hardi, Graham A. Colditz, Adetunji T. Toriola. Weight gain after age 18 and breast cancer risk: A meta-analysis [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 732.

Association of Serum 25-Hydroxyvitamin D Concentration with Breast Cancer Risk in Postmenopausal Women in the US.

The association between serum 25-hydroxyvitamin D [25(OH)D] concentration and breast cancer risk in postmenopausal women is not well understood. The aim of this study was to investigate the association between serum 25(OH)D concentration and breast cancer in postmenopausal women in the United States using nationally representative sample surveys. We used the data from seven cycles of National Health and Nutrition Examination Surveys from 2001 to 2014. Participants were non-institutionalized postmenopausal women (n = 8108). In restricted cubic spline analysis, a significant, nonlinear, invert ‘U’ relationship was observed between serum 25(OH)D concentrations and breast cancer in postmenopausal women (p = 0.029). Overall, breast cancer risk was highest (OR = 1.5) between 70 nmol/L and 80 nmol/L of serum 25(OH)D concentration. Then after serum 25(OH)D 80 nmol/L concentration, the breast cancer risk declined. In multivariate-adjusted logistic regression, the risk of having breast cancer was significantly higher in serum 25(OH)D 75–˂100 nmol/L category compared to the 25(OH)D < 30 nmol/L category [OR and 95% CI: 2.4 (1.4–4.0)]. In conclusion, serum vitamin D concentrations ≥ 100 nmol/L are associated with reduced risk of breast cancer in postmenopausal women. Controlled trials are required to verify if serum 25(OH)D ≥ 100 nmol/L offers protection against breast cancer in postmenopausal women.

Metabolic Profile, Biotransformation, Docking Studies and Molecular Dynamics Simulations of Bioactive Compounds Secreted by CG3 Strain.

Actinobacteria isolated from untapped environments and exposed to extreme conditions such as saltpans are a promising source of novel bioactive compounds. These microorganisms can provide new molecules through either the biosynthetic pathway or the biotransformation of organic molecules. In the present study, we performed a chemical metabolic screening of secondary metabolites secreted by the new strain CG3, which was isolated from a saltpan located in the Sahara of Algeria, via high-performance liquid chromatography coupled with high-resolution mass spectrometry (HPLC-ESI-HRMS). The results indicated that this strain produced five new polyene macrolactams, kenalactams A–E, along with two known compounds, mitomycin C and 6″-hydroxy-4,2′,3′,4″ tetramethoxy-p-terphenyl. Furthermore, the CG3 isolate could have excellent properties for converting the aglycone isoflavone glycitein to the compounds 6,7-dimethoxy-3-(4-methoxyphenyl)chromen-4-one (50) and 6,7-dimethoxy-3-phenylchromen-4-one (54), and the isoflavone genistein can be converted to 5,7-dimethoxy-3-(4-methoxyphenyl)chromen-4-one (52). Docking studies and molecular dynamics simulations indicated that these three isoflavones, generated via biotransformation, are potent inhibitors of the target protein aromatase (CYP19A1); consequently, they can be used to prevent breast cancer risk in postmenopausal women.

Could Self-Reported Body Sizes Be an Alternative Tool for Assessing Breast Cancer Risk in Postmenopausal Women?

Background: The use of self-reported body size as an alternative tool to estimate body weight for health risk assessment is not widely reported, especially in relation to breast cancer. Therefore, we examined the association between breast cancer and body-mass index (BMI) and the usefulness of pictograms. Methods: The case–control study was conducted among postmenopausal women from 2015 to 2019. The study involved 151 women with breast cancer and 67 control subjects. Data were collected by a self-reported detailed questionnaire. Results: An increased, 4.13-fold risk of breast cancer (OR = 4.13; 95% CI [1.69, 10.28]) was observed for women with BMI 25.0–29.9 kg/m2 compared to women with normal BMI (18.5–24.9 kg/m2), whereas the association in the case of obese women was not statistically significant. An increased risk of breast cancer was observed for pictogram scores 3–4 (OR = 8.95; 95% CI [3.22, 24.88]) and for the highest level of self-reported body size, pictograms ≥ 5 (OR = 3.20; 95% CI [1.13, 9.09]). Conclusions: The risk of breast cancer is associated with an increased BMI and visual overweigh and obesity. The results suggest that a self-reporting alternative tool can be used to assess the prevalence of overweight/obesity, particularly in situations where no other tools are available.

Adiposity and breast, endometrial, and colorectal cancer risk in postmenopausal women: Quantification of the mediating effects of leptin, C-reactive protein, fasting insulin, and estradiol.

BackgroundMechanisms underlying the adiposity–cancer relationship are incompletely understood. We quantified the mediating roles of C‐reactive protein (CRP), leptin, fasting insulin, and estradiol in the effect of adiposity on estrogen receptor (ER)‐positive breast, endometrial, and colorectal cancer risk in postmenopausal women.MethodsWe used a case–cohort study within the Women's Health Initiative Observational Study, analyzed as a cumulative sampling case–control study. The study included 188 breast cancer cases, 98 endometrial cancer cases, 193 colorectal cancer cases, and 285 controls. Interventional indirect and direct effects on the risk ratio (RR) scale were estimated using causal mediation analysis.ResultsFor breast cancer, the total effect RR for BMI ≥30 versus ≥18.5–<25 kg/m2 was 1.87 (95%CI,1.11–3.13). The indirect effect RRs were 1.38 (0.79–2.33) through leptin and CRP, 1.58 (1.17–2.43) through insulin, and 1.11 (0.98–1.30) through estradiol. The direct effect RR was 0.82 (0.39–1.68). For endometrial cancer, the total effect RR was 2.12 (1.12–4.00). The indirect effect RRs were 1.72 (0.85–3.98) through leptin and CRP, 1.42 (0.96–2.26) through insulin, and 1.24 (1.03–1.65) through estradiol. The direct effect RR was 0.70 (0.23–2.04). For colorectal cancer, the total effect RR was 1.70 (1.03–2.79). The indirect effect RRs were 1.04 (0.61–1.72) through leptin and CRP, 1.36 (1.00–1.88) through insulin, and 1.02 (0.88–1.17) through estradiol. The direct effect RR was 1.16 (0.58–2.43).ConclusionLeptin, CRP, fasting insulin, and estradiol appear to mediate the effect of high BMI on cancer risk to different extents, with likely varying degrees of importance between cancers. These insights might be important in developing interventions to modify obesity‐associated cancer risk in postmenopausal women.

Recreational Physical Activity, Sitting, and Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study

Prolonged sitting and physical inactivity are associated with higher circulating levels of estrogens. It is unknown whether these risk factors are associated with circulating androgens/androgen metabolites, another set of hormones implicated in the etiology of cancers in postmenopausal women. We conducted a cross-sectional analysis of 1,782 postmenopausal women in the Women's Health Initiative Observational Study. Serum concentrations of 12 androgens/androgen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Physical activity and sitting time were self-reported at baseline. We performed linear regression to estimate geometric means (GM) of androgen/androgen metabolite concentrations (pmol/L) according to physical activity and sitting time, adjusting for potential confounders and stratified by menopausal hormone therapy (MHT) use. Physical activity (≥15 vs. 0 MET-h/wk) was inversely associated with estrogen-to-androgen ratios among never/former MHT users (adj-GM = 37.5 vs. 49.6 unconjugated estrone:androstenedione; 20.2 vs. 30.3 unconjugated estradiol:testosterone; all P trend ≤ 0.03) but was not associated among current MHT users. Prolonged sitting (≥10 vs. ≤5 h/d) was positively associated with these ratios among both never/former (adj-GM = 44.2 vs. 38.3, P trend = 0.10; adj-GM = 23.4 vs. 20.2, P trend = 0.17; respectively) and current MHT users (adj-GM = 197 vs. 147; 105 vs. 75.5; respectively; all P trend ≤0.02), but the associations were statistically significant among current MHT users only. The associations persisted after adjustment for BMI. After adjustment for adrenal androgens, physical activity and sitting were not associated with androgen metabolites. Physical activity and sitting were associated with serum estrogen-to-androgen ratios but not androgen metabolites. This study contributes to our understanding of the link between physical activity, sitting, and cancer risk in postmenopausal women.

Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis.

BackgroundObservational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.MethodsWe investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone–binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.ResultsIn the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], Ptrend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk.ConclusionOur observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.

The Effects of Diet and Exercise on Endogenous Estrogens and Subsequent Breast Cancer Risk in Postmenopausal Women.

Endogenous estrogens have been associated with overall breast cancer risk, particularly for postmenopausal women, and ways to reduce these estrogens have served as a primary means to decrease overall risk. This narrative review of clinical studies details how various nutritional and exercise lifestyle interventions have been used to modify estrogen levels and metabolism to provide a protective impact against breast cancer incidence. We also summarized the evidence supporting the efficacy of interventions, outcomes of interest and identified emerging research themes. A systematic PubMed MEDLINE search identified scholarly articles or reviews published between 2000-2020 that contained either a cohort, cross-sectional, or interventional study design and focused on the relationships between diet and/or exercise and overall levels of different forms of estrogen and breast cancer risk and occurrence. Screening and data extraction was undertaken by two researchers. Data synthesis was narrative due to the heterogeneous nature of studies. A total of 1625 titles/abstracts were screened, 198 full texts reviewed; and 43 met eligibility criteria. Of the 43 studies, 28 were randomized controlled trials, and 15 were observational studies. Overall, studies that incorporated both diet and exercise interventions demonstrated better control of detrimental estrogen forms and levels and thus likely represent the best strategies for preventing breast cancer development for postmenopausal women. Some of the strongest associations included weight loss via diet and diet + exercise interventions, reducing alcohol consumption, and consuming a varied dietary pattern, similar to the Mediterranean diet. More research should be done on the effects of specific nutritional components on endogenous estrogen levels to understand the effect that the components have on their own and in combination within the diet.

Obesity, Height, and Serum Androgen Metabolism among Postmenopausal Women in the Women's Health Initiative Observational Study.

Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers. Using baseline data from 1,765 postmenopausal women in the Women's Health Initiative Observational Study, we conducted a cross-sectional analysis examining associations between anthropometric measures [current body mass index (BMI), waist-to-hip ratio (WHR), height, and recalled BMI at age 18) and serum androgen metabolites. Twelve androgens/androgen metabolites were quantified using LC-MS/MS. Geometric means of androgen/androgen metabolite concentrations were estimated using linear regression, adjusting for potential confounders and stratified by hormone therapy (HT) use. Regardless of HT use, higher current BMI (≥30 vs. <25 kg/m2) was associated with higher serum concentrations of dehydroepiandrosterone sulfate (DHEAS), 5α-reduced glucuronide metabolites [androsterone-glucuronide (ADT-G), 5α-androstane-3α,17β diol-3-glucuronide (3α-diol-3G), 3α-diol-17-glucuronide (3α-diol-17G)], and DHEAS:DHEA ratio (all P trend ≤ 0.02). BMI was also positively associated with unconjugated estrone:androstenedione and unconjugated estradiol:testosterone ratios among never/former HT users (all P trend < 0.001) but not among current users (P-int < 0.001). WHR was positively associated with adrenal androgens and 5α-reduced glucuronide metabolites in obese women only (BMI ≥ 30 kg/m2; all P-trend ≤ 0.01). BMI at age 18 was inversely associated with adrenal androgens (DHEA, DHEAS, androstenedione, testosterone) and 5α-reduced glucuronide metabolites in never/former HT users (all P trend < 0.06). Height was not associated with androgen metabolites. Current BMI is associated with androgen metabolism among postmenopausal women. This study contributes to our understanding of the link between obesity and cancer risk in postmenopausal women.

Korean red ginseng induces extrinsic and intrinsic apoptotic pathways in MCF-7 breast cancer cells and MCF-10A non-malignant breast cells.

Among non-hormonal treatments, herbal products are frequently used by women. Korean red ginseng (KRG) is one of the popular herbal medicines. KRG could be one option for relieving menopausal symptoms. However, there are still concerns about the safety for long-term use. In order to be used for alleviating menopausal symptoms, the safety of KRG on breast must be ensured. The purpose of this study was to investigate the effects of KRG on breast cells. MCF-7 and MCF-10A cells were treated with different concentrations of KRG extracts for 48 h. Cell viability was evaluated by MTT assay, and apoptosis by flow cytometry. The expression of apoptosis-related proteins was determined by western blot analysis and estrogen receptor (ER) affinity by ER binding assay. KRG extract inhibited growth and induced apoptosis of both MCF-7 and MCF-10A cells in dose-dependent manner. KRG extract increased the expression of pro-apoptotic proteins BAX, BAK, and BAD and decreased the expression of anti-apoptotic proteins Bcl-2 and Bcl-XL in both cells. The expressions of Fas and FasL were increased in lower doses, but decreased in higher doses in both cells. Activities of caspase-3, -8 and -9 increased in MCF-10A, while caspase-8 and -9 showed increase in MCF-7. Competition of KRG to E2 was significant in MCF-7 as KRG dose increased, whereas ER binding was hardly shown in MCF-10. KRG induced apoptosis via extrinsic and intrinsic pathway in MCF-7 breast cancer cells and MCF-10A non-malignant cells. KRG may be safely used with regard to breast cancer risk in postmenopausal women to reduce the vasomotor symptoms.