SGLT2 Inhibitor Use and Risk of Breast Cancer Among Adult Women with Type 2 Diabetes.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antihyperglycemic agents, with the potential to inhibit breast cancer development. However, the association between SGLT2 inhibitors and risk of breast cancer in human studies is unclear. OBJECTIVE: The aim of our study is to use a large national claims database to assess the association between SGLT2 inhibitor use and risk of breast cancer. METHODS: We considered a study population of 158,483 adult women with type 2 diabetes who newly initiated SGLT2 inhibitors or dipeptidyl peptidase 4 (DPP4) inhibitors using Optum's deidentified Clinformatics Data Mart Database between 1 January 2013 and 31 March 2022. The association between SGLT2 inhibitor use and risk of breast cancer was examined using Cox proportional hazard models stratified by age in the overall sample and in a subsample based on propensity score and medication initiation time matching. The effect of medication use duration was explored. RESULTS: With an average follow-up of 2.2 years, 2154 breast cancer cases were identified. There was no significant association between SGLT2 inhibitor use and the risk of breast cancer in overall sample (HR = 0.96; 95% CI 0.87, 1.06), in women younger than 51 years old (HR = 0.88; 95% CI 0.59, 1.32), or in women aged 51 years or older (HR = 0.95; 95% CI 0.86, 1.04). The results remained nonsignificant using matching, medication use duration, and sensitivity analyses. CONCLUSION: Our findings suggest SGLT2 inhibitors use was not associated with breast cancer risk compared with DPP4 inhibitors use. Studies with longer follow-up and better adjustments are needed to confirm the finding.

Hysterectomy, oophorectomy and risk of non-Hodgkin's lymphoma.

Hysterectomy is associated with an increased risk for adverse health outcomes. However, its connection to the risk of non-Hodgkin's lymphoma (NHL) remains unclear. The aims of our study were to investigate the associations between hysterectomy, oophorectomy and risk of NHL and its major subtypes (eg, diffuse large B-cell lymphoma [DLBCL]), and whether these associations were modified by exogenous hormone use. Postmenopausal women (n = 141,621) aged 50-79 years at enrollment (1993-1998) from the Women's Health Initiative were followed for an average of 17.2 years. Hysterectomy and oophorectomy were self-reported at baseline. Incident NHL cases were confirmed by central review of medical records and pathology reports. During the follow-up period, a total of 1719 women were diagnosed with NHL. Hysterectomy, regardless of oophorectomy status, was associated with an increased risk of NHL (hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.05-1.44). Oophorectomy was not independently associated with NHL risk after adjusting for hysterectomy. When stratified by hormone use, the association between hysterectomy and NHL risk was confined to women who had never used hormone therapy (HR = 1.35, 95% CI: 1.06-1.71), especially for DLBCL subtype (P for interaction = .01), and to those who had undergone hysterectomy before the age of 55. Our large prospective study showed that hysterectomy was a risk factor of NHL. Findings varied by hormone use. Future studies incorporating detailed information on the types and indications of hysterectomy may deepen our understanding of the mechanisms underlying DLBCL development and its potential interactions with hormone use.

Optimal objective measurement of physical function and its predictive capacity for mortality among community-dwelling older women.

AIM: Objective measurements of physcial function, including gait speed, handgrip strength, and the chair stand test, have been shown to have predictive capacity for negative health-related outcomes. The aim of this study was to examine campariatively which of these common assessments may be optimal in terms of their predictive capacity for mortality. METHODS: A total of 9834 community-dwelling older women aged 65-89 years from the Study of Osteoporotic Fractures (SOF) were followed for 20 years. Gait speed, handgrip strength, and the chair stand test were measured every 2-4 years on up to 9 visits. All deaths were adjudicated. RESULTS: All three measurements of physical function were significantly associated with overall, cardiovascular disease and other mortality. Gait speed had the greatest magnitude of hazard ratios (HRs) for all outcomes of interest. A one-unit standard deviation increase in gait speed was associated with a 33% (HR = 0.67, 95% confidence interval [95% CI]: 0.64-0.70) lower risk for overall mortality, a 31% (HR = 0.69, 95% CI: 0.64-0.73) lower risk for cardiovascular disease mortality, a 15% (HR = 0.85, 95% CI: 0.78-0.92) lower risk for cancer mortality and a 42% (HR = 0.58, 95% CI: 0.55-0.62) lower risk for other mortality. Further examination of gait speed identified two cut-points (0.9 and 0.7 m/s) that were strongly indicative of increased mortality risk. CONCLUSION: Our large prospective study indicates that gait speed possesses a better prediction of mortality among older women compared with handgrip strength or the chair stand test. Using cut-points of 0.9 and 0.7 m/s can help identify older women at higher mortality risk, who may benefit from physical function improvement interventions. Geriatr Gerontol Int 2023; 23: 715-721.

Birth weight, adult body size, and risk of colorectal cancer.

BACKGROUND: Evidence suggests that birth weight may be associated with colorectal cancer (CRC) risk later in life. Whether the association is mediated by adult body size remains unexamined. METHOD: Cox proportional hazards models (Hazard Ratio (HR) and 95 % Confidence Intervals (CI)) were used to evaluate the association between self-reported birth weight (<6 lbs, 6-<8 lbs, ≥8 lbs) and CRC risk among 70,397 postmenopausal women from the Women's Health Initiative. Further, we assessed whether this association was mediated by adult body size using multiple mediation analyses. RESULTS: Compared with birth weights of 6-< 8 lbs, birth weight ≥ 8 lbs was associated with higher CRC risk in postmenopausal women (HR = 1.31, 95 % CI 1.16-1.48). This association was significantly mediated by adult height (proportion mediated =11.4 %), weight (11.2 %), waist circumference (10.9 %), and body mass index at baseline (4.0 %). The joint effect of adult height and weight explained 21.6 % of this positive association. CONCLUSION: Our data support the hypothesis that the intrauterine environment and fetal development may be related to the risk of developing CRC later in life. While adult body size partially explains this association, further investigation is required to identify other factors that mediate the link between birth weight and CRC.

A Longitudinal Study of Sleep Habits and Leukemia Incidence Among Postmenopausal Women.

We sought to assess the relationship between sleep duration, sleep disturbance, and leukemia incidence among postmenopausal women. This study included 130,343 postmenopausal women aged 50-79 years who were enrolled in the Women's Health Initiative (WHI) during 1993-1998. Information on self-reported typical sleep duration and sleep disturbance was obtained by questionnaire at baseline, and sleep disturbance level was defined according to the Women's Health Initiative Insomnia Rating Scale (WHIIRS). WHIIRS scores of 0-4, 5-8, and 9-20 comprised 37.0%, 32.6%, and 30.4% of all women, respectively. After an average of 16.4 years (2,135,109 cumulative person-years) of follow-up, 930 of the participants were identified as having incident leukemia. Compared with women with the lowest level of sleep disturbance (WHIIRS score 0-4), women with higher sleep disturbance levels (WHIIRS scores of 5-8 and 9-20) had 22% (95% confidence interval (CI): 1.04, 1.43) and 18% (95% CI: 1.00, 1.40) excess risks of leukemia, respectively, after multivariable adjustment. A significant dose-response trend was found for the association between sleep disturbance and leukemia risk (P for trend = 0.048). In addition, women with the highest level of sleep disturbance had a higher risk of myeloid leukemia (for WHIIRS score 9-20 vs. WHIIRS score 0-4, hazard ratio = 1.39, CI: 1.05, 1.83). Higher sleep disturbance level was associated with increased risk of leukemia, especially for myeloid leukemia among postmenopausal women.

Body size over the adult life course and the risk of colorectal cancer among postmenopausal women.

OBJECTIVE: To assess the associations among several anthropometric measures, as well as BMI trajectories and colorectal cancer (CRC) risk in older women. DESIGN: Prospective cohort study. SETTING: Forty clinical centres in the USA. PARTICIPANTS: Totally, 79 034 postmenopausal women in the Women's Health Initiative Observational Study. RESULTS: During an average of 15·8 years of follow-up, 1514 CRC cases were ascertained. Five BMI trajectories over 18-50 years of age were identified using growth mixture model. Compared with women who had a normal BMI at age 18, women with obesity at age 18 had a higher risk of CRC (HR 1·58, 95 % CI 1·02, 2·44). Compared with women who kept relatively low normal body size during adulthood, women who progressed from normal to obesity (HR 1·29, 95 % CI 1·09, 1·53) and women who progressed from overweight to obesity (HR 1·37, 95 % CI 1·13, 1·68) had higher CRC risks. A weight gain > 15 kg from age 18 to 50 (HR 1·20, 95 % CI 1·04, 1·40) and baseline waist circumference > 88 cm (HR 1·33, 95 % CI 1·19, 1·49) were associated with higher CRC risks, compared with stable weight and waist circumference ≤ 88 cm, respectively. CONCLUSION: Women who have a normal weight in early adult life and gain substantial weight later, as well as those who are persistently heavy over adulthood, demonstrated a higher risk of developing CRC. Our study highlights the importance of maintaining a healthy body weight over the life course for reducing the risk of developing CRC in women.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-small cell lung cancer survival.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs with demonstrated renal and cardiovascular disease benefit. This study evaluates the role of SGLT2 inhibitors on the survival of non-small cell lung cancer (NSCLC) patients. METHODS: We used National Surveillance, Epidemiology and End Results (SEER)-Medicare linked data. Twenty four thousand nine hundred fifteen NSCLC patients newly diagnosed between 2014 and 2017 with pre-exiting diabetes and aged 66 years or older were included and followed to the end of 2019. Information on SGLT2 inhibitors use was extracted from the Medicare Part D file. RESULTS: SGLT2 inhibitor use was associated with significantly reduced mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.60-0.77) with stronger association for longer duration of use (HR = 0.54, 85% CI = 0.44-0.68). Further, we found that SGLT2 inhibitor use was associated with a significant reduced risk of mortality regardless of patients' demographic, tumour characteristics and cancer treatments. CONCLUSION: Our large SEER-Medicare linked data study indicates that SGLT2 inhibitors use was associated with improved overall survival of NSCLC patients with pre-existing diabetes. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.

Long-term changes of cognitive impairment among older breast cancer survivors.

PURPOSE: Cancer-related cognitive impairment is common during cancer treatment; however, it is unclear whether the impairment persists over time. Our study aimed to examine long-term cognitive impairment among older breast cancer survivors. METHODS: Participants included 2420 community-dwelling women aged 65 years or older at enrollment (1986-1988) (404 breast cancer cases and 1:5 matched cancer-free controls) from the Study of Osteoporotic Fractures. Participants were followed for 20 years with measured cognitive function repeated up to 6 times. Cognitive impairment was defined by the Modified Mini-Mental State Examination and Trail Making Test B. Generalized linear models were used to model risk of cognitive impairment in relation to breast cancer status and time from breast cancer diagnosis. RESULTS: Compared with controls, cognitive impairment in women with breast cancer significantly accelerated after cancer diagnosis. We also observed a more pronounced cognitive impairment after cancer diagnosis for women diagnosed with breast cancer at age ≥ 80 years or at advanced stage for both measures. CONCLUSION: Our study with more than 20 years of follow-up data found that breast cancer survivors had accelerated cognitive impairment after cancer diagnosis, especially among women diagnosed at older age or at advanced stage, relative to women without cancer. IMPLICATIONS FOR CANCER SURVIVORS: Breast cancer survivors may be encouraged to engage in both physical activity and cognitive training.

Gait speed, handgrip strength, and cognitive impairment among older women - A multistate analysis.

BACKGROUND: Cognitive impairment imposes substantial psychological, emotional, and economic burdens on affected individuals, families and society. A better understanding of potentially modifiable risk factors that may be used in the prevention of cognitive impairment is therefore a high priority in aging research. METHODS: This study included 9268 community-dwelling women aged 65 years or older from the Study of Osteoporotic Fractures launched between 1986 and 1988 in the US. Participants were followed for 20 years. Modified Mini-Mental State Examination (m-MMSE) was administered up to 6 times. Six updated measurements of gait speed and handgrip strength at the same visit time when m-MMSE was administered were used. The m-MMSE score was used to define cognitive impairment states (normal, mild, and severe impairment). A multi-state model (MSM) was used to estimate the transitions between different states of cognitive function. RESULTS: Faster gait speed (one unit increase of meter/s) was associated with lower risk of transition from cognitively normal status to mild cognitive impairment (HR = 0.50, 95 % CI: 0.37-0.67), and from mild impairment to severe impairment (HR = 0.52, 95 % CI: 0.37-0.72). Higher gait speed was associated with increased risk of cognitive transition from severe impairment to mild impairment (HR = 2.56 95 % CI: 0.97-6.77), although the result did not reach statistical significance. Similarly, we observed greater handgrip strength (per kg increase) was associated with lower risk of transition of cognitive status from normal to mild impairment (HR = 0.96 95 % CI: 0.95-0.97), and from mild to severe impairment (HR = 0.98, 95 % CI: 0.96-0.99). Greater handgrip strength was associated with increased risk of cognitive transition from severe to mild cognitive impairment (HR = 1.05, 95 % CI: 1.01-1.09). In addition, we also observed that both faster gait speed and greater handgrip strength were associated with lower risk of transitions from normal or mild cognitive impairment status to death. CONCLUSION: Our results confirmed that screening for slow gait speed or weak handgrip strength may be useful for identifying older adults at risk for cognitive decline when they are still cognitively normal or only mildly impaired. Exercise programs to improve gait speed and muscle strength may delay or prevent transitions into cognitive impairment in older adults.

Sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation and hepatocellular carcinoma prognosis.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. Emerging findings from laboratory studies indicate that SGLT2 inhibitors can improve liver function and suppress the proliferation of hepatocellular carcinoma (HCC) cells. The aim of this study was to test the hypothesis that initiation of SGLT2 inhibitors improves HCC prognosis in a human population. METHODS: We used National Surveillance, Epidemiology and End Results (SEER)-Medicare linked data in the United States to evaluate the role of SGLT2 inhibitor initiation on the survival of HCC patients. 3,185 HCC patients newly diagnosed between 2014 and 2017 aged 66 years or older with pre-existing type 2 diabetes were included and followed to the end of 2019. Information on SGLT2 inhibitor initiation was extracted from the Medicare Part D file. RESULTS: SGLT2 inhibitor initiation was associated with significantly lower mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.54-0.86) with stronger association for longer duration of use (HR = 0.60, 95% CI = 0.41-0.88). Further, we found that SGLT2 inhibitor initiation was associated with a lower risk mortality risk ranging from 14% to 60% regardless of patient demographic variables, tumor characteristics, and cancer treatments. CONCLUSION: Our large SEER-Medicare linked data study indicates that SGLT2 inhibitor initiation was associated with improved overall survival of HCC patients with pre-existing type 2 diabetes compared with no SGLT2 inhibitor use. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.

Dietary selenium intake and thyroid cancer risk in postmenopausal women.

OBJECTIVE: It 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. METHODS: The 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. RESULTS: During 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). CONCLUSIONS: The 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.

Trajectories of objectively measured physical function among older breast cancer survivors in comparison with cancer-free controls.

PURPOSE: Aging associated with progressive declines in physical function is well-known; however, it is unclear how breast cancer diagnosis affects the trajectories of physical function over a long period of time. The current study examined the trajectories in objective measures of physical function over 20 years for women with breast cancer and matched controls. METHODS: 2712 community-dwelling women (452 breast cancer cases and 1:5 matched cancer-free controls) aged 65 years or older at baseline (1986-1988) within the Study of Osteoporotic Fractures were followed for 20 years. Objective physical function was assessed up to 9 times, including hand grip strength, timed chair stand, gait speed and quadriceps strength. Linear mixed models were used to model physical function changes in terms of secular time trend, group (cases or controls), period (pre-and post-diagnosis status), and their interaction terms. RESULTS: We observed all measures of physical function declined over time. While no differences in trends between cases and controls during the pre-diagnosis period were observed, after cancer diagnosis, grip strength and gait speed declined significantly faster in cases than controls. Quadriceps strength significantly decreased ~ 7 pounds shortly after breast cancer diagnosis, and then improved over time. CONCLUSION: Our study revealed that older breast cancer survivors relative to older women without cancer had significantly worse declines in grip strength and gait speed. Breast cancer survivors also had a sharp, short-term drop followed by gradual improvement over time in quadriceps strength. These findings suggest exercise training targeting muscle strength and mobility would be beneficial among older breast cancer survivors.

Mortality disparities between Black and White Americans mediated by income and health behaviors.

BACKGROUND: Race disparities in health outcomes including mortality risk are well known, but mediating mechanisms that link race to mortality risk have rarely been formally tested. METHODS: We analyzed public NHANES III data from 1988 to 1994 linked to mortality outcomes prospectively through 2015. Participants included 10,460 non-Hispanic Black (40.5%, n = 4233) and non-Hispanic White (59.5%, n = 6227) adults. Proportional hazards regression models examined mortality risk in association with race, demographics, income, and an index of risky health behaviors including smoking, poor diet and low physical activity. A mediation approach under the counterfactual framework was used to test effects of income and risky health behaviors as mediators between race and mortality risk. RESULTS: Considering only race, age and sex, Black participants had significantly higher mortality risk than Whites (HR = 1.46, 95% CI 1.35-1.58). When income and education were added, the race effect was lower but remained significant (HR = 1.15, 95% CI 1.02-1.30). In the subsequent model that also included risky behaviors the association between race and mortality was no longer significant (HR = 1.05, 95% CI 0.92-1.20); both higher income and healthier behaviors contributed to lower mortality risk. There was a significant indirect effect of race on mortality mediated through income, and the direct effect of race on mortality was not significant when the mediating effect of income was considered. Likewise, the risky behavior score significantly mediated the association between race with mortality, and the direct effect of race was not significant. In the separate models, income mediated 62% of the association between race and mortality and lifestyle mediated 61% of the relationship. CONCLUSIONS: Efforts to reduce race-based mortality disparities may focus on policies to reduce income-based disparities and promote positive health behaviors that consider variations in socioeconomic resources and personal preferences.

Mediation analysis of social isolation and mortality by health behaviors.

Social isolation associated with greater risk for mortality is well documented, however, it is unclear whether and the extent to which social isolation influences mortality through health behaviors. We therefore assessed the mediation between social isolation and mortality by health behaviors. 15,000 adults ages 18-89 years in the Third National Health and Nutrition Examination Survey in the US (NHANES III) (1988-1994) were followed through 2015. The outcomes of overall and cause-specific mortality were assessed by linking with the National Death Index. Social isolation was based on a modified Social Network Index. Mediation analyses were conducted under the counterfactual framework. Compared with participants who were not socially isolated, those who were isolated had significantly increased risk for overall mortality (HR = 1.33, 95% CI: 1.15-1.54), cardiovascular disease (CVD)-specific mortality (HR = 1.28, 95% CI: 1.01-1.62) and mortality from causes other than CVD or cancer (HR = 1.53, 95% CI: 1.22-1.90). Social isolation was not independently associated with risk for cancer-specific mortality. The association between social isolation and cancer-specific mortality was largely (74%) mediated by health behaviors, including smoking, physical activity and quality of diet. The associations between social isolation and CVD or other specific mortality were partly (about one-fifth) explained by unhealthy behaviors. In conclusion, the extent to which social isolation and mortality was mediated by healthy behaviors varies by causes of death. Given mounting evidence that social isolation is increasing in society, it is important to add social isolation to the list of public health concerns in addition to conventional risk factors.

Association between exposure to parabens and total mortality in US adults.

BACKGROUND: Parabens are a group of endocrine disruptors that have been associated with health effects such as hypertension, diabetes, oxidative stress and obesity, which are associated with increased mortality risk over time. Women are exposed to higher paraben levels than men through use of consumer products. The current prospective study examines paraben exposure in association with mortality risk for women and men. METHODS: We analyzed 2005-2008 National Health and Nutrition Examination Survey (NHANES) data on urinary paraben analyte concentrations and covariates in adults aged 20 years and over, prospectively linked to National Center for Health Statistics (NCHS) mortality through 2015 (N = 2939). Proportional hazard regression models examined mortality risk in association with exposures, controlling for covariates for women and men. Covariates included age, race/ethnicity, smoking, education, income, body mass index, physical activity, self-reported health status and baseline health conditions. RESULTS: Women were exposed to significantly higher concentrations of all studied parabens than men. Exposures were highest for methyl paraben. Women had significantly higher mortality risk in association with higher natural log exposure to ethyl (HR = 2.048, 95% CI 1.164-3.601), methyl (HR = 1.312, 95% CI 1.013-1.700), butyl (HR = 2.719, 95% CI 1.591-4.647) and total parabens (HR = 1.292, 95% CI 1.006-1.659). Exposure concentrations were associated with higher mortality risk for men only for ethyl paraben (HR = 2.532, 95% CI 1.217-5.268). DISCUSSION: Women were found to be at greater mortality risk in association with exposure to ethyl, methyl, butyl and total parabens. These findings require confirmatory research but add to the evidence base that exposure to parabens, probably through consumer products, may have adverse effects on human health, especially for women.

Risk Patterns and Mortality in Postmenopausal Women Using Latent Class Analysis.

INTRODUCTION: Although risk factors often co-occur, previous studies examining lifestyle or psychosocial factors often treat these factors as individual predictors of health. This study aims to identify the underlying subgroups of women characterized by distinct lifestyle and psychosocial risk patterns and to investigate the prospective associations between risk patterns and mortality among postmenopausal women. METHODS: A total of 64,812 postmenopausal women aged 50-79 years without prevalent diabetes, cardiovascular disease, and cancer at baseline (1993-1998) were followed until 2019 with a mean follow-up duration of 14.6 (SD=6.4) years. Latent class analysis was used to identify the latent classes of women with homogeneous combinations of lifestyle and psychosocial variables and to test whether the classes were prospectively associated with mortality. Analyses were stratified by race/ethnicity and were performed in 2020. RESULTS: A total of 4 latent classes (Healthy Lifestyle and Psychosocial, Risky Psychosocial, Risky Lifestyle, and Risky Lifestyle and Risky Psychosocial) were identified for Hispanic, Black, and White women, and 2 classes (High Risk or Low Risk) were identified for American Indian and Asian women. Women in the Risky Lifestyle and Risky Psychosocial group had the highest hazard ratios for all outcomes studied for all race/ethnicity groups than those in the Healthy Lifestyle and Psychosocial group, followed by those in the Risky Lifestyle group. Risky Psychosocial class was significantly associated with an elevated risk of overall and cardiovascular disease mortality only in Black women. CONCLUSIONS: The class with concurrent risky lifestyle and psychosocial factors conveyed the greatest risk of all types of mortality than a low-risk ref group. Health promotion should address both behavioral and psychosocial risks concurrently.

Mediation analysis of racial disparities in triple-negative breast cancer incidence among postmenopausal women.

BACKGROUND: Triple-negative breast cancer (TNBC) is disproportionately higher in Black women relative to White women. The objective of this study was to examine to what extent the association between race/ethnicity and risk of TNBC is mediated by potentially modifiable factors. METHODS: A total of 128,623 Black and White women aged 50-79 years from the Women's Health Initiative were followed for a mean of 15.8 years. 643 incident TNBC cases (92 Black women and 551 White women) were confirmed by medical record review. Mediation analyses were conducted using an approach under a counterfactual framework. RESULTS: Black women had approximately twofold higher risk of TNBC compared with white women (HR = 1.93, 95% CI 1.52-2.45). We observed that 48% of the racial disparity was mediated by metabolic dysfunction defined by having 3 or more cardiometabolic risk factors including elevated waist circumference, having history of diabetes, high cholesterol and hypertension. The racial disparity was not significantly mediated by other factors studied, including socioeconomic, lifestyle or reproductive factors. CONCLUSION: Our study observed that approximately half of the racial disparity between postmenopausal Black and White women in TNBC incidence was driven by metabolic dysfunction.

Health information source use and trust among a vulnerable rural disparities population.

PURPOSE: Because rural residents, particularly those near mining sites, are susceptible to numerous environmental health hazards, it is important to gain deeper insights into their use and trust of health information, which they may employ to help recognize symptoms, learn ways to reduce exposure, or find health care. METHODS: We surveyed residents (N = 101) of rural Kentucky, Virginia, and West Virginia to assess predictors of health information source use and trust. A project manager administered face-to-face paper and pencil questionnaires assessing demographics, health status, smoking behavior, and health information use and source trust. Bivariate correlations and ordinary least squares regressions were used to analyze the data. FINDINGS: The data suggest that rural individuals frequently use nurses, doctors, and websites to seek health information, whereas traditional media are often not their preferred channel for health information. Media sources were not found as trustworthy as interpersonal and medical health information sources. While only 13.0% of individuals in the sample said they ever turned to county or state health departments for health information, these sources were trusted more than any media source and more than friends. Moreover, living closer to active mining sites-meaning these individuals are at a higher risk of environmental health hazards-predicted even less use of traditional media and greater trust in peer sources. CONCLUSIONS: Not all sources of health information are equally used or trusted by individuals from a rural disparities population. The findings have implications for health campaign message dissemination and intervention designs targeting individuals in rural Appalachia.

BMI trajectory and subsequent risk of type 2 diabetes among middle-aged women.

BACKGROUND AND AIMS: Little is known about how weight trajectories among women during menopausal transition and beyond may be related to risk of type 2 diabetes mellitus (T2DM). The aim of this study was to examine associations between body mass index (BMI) trajectories over 20 years, age of obesity onset, cumulative obese-years and incidence of T2DM among middle-aged women. METHODS AND RESULTS: 12,302 women enrolled in the Australian Longitudinal Study on Women's Health (ALSWH) were surveyed in 1996 (Survey 1, age 45-50), 1998 and then every three years to 2016. Self-reported weight and height were collected for up to eight time points. Incident diabetes was assessed via validated self-report of physician-diagnosed diabetes. Growth mixture models were used to identify distinct BMI trajectories. A total of 1380 (11.2%) women newly developed T2DM over an average 16 years of follow-up. Seven distinct BMI trajectories were identified with differential risk of developing T2DM. Initial BMI was positively associated with T2DM risk. We also observed that risk of T2DM was positively associated with rapid weight increase, early age of obesity onset and greater obese-years. CONCLUSION: Slowing down weight increases, delaying the onset of obesity, or reducing cumulative exposure to obesity may substantially lower the risk of developing T2DM.