Development and Validation of Body Mass Index-Specific Waist Circumference Thresholds in Postmenopausal Women : A Prospective Cohort Study.

Background: A 2020 consensus statement proposed body mass index (BMI)-specific waist circumference (WC) thresholds to improve patient care.

Objective: To determine whether stratifying BMI categories by BMI-specific WC thresholds improves mortality risk prediction.

Design: Prospective cohort study.

Comorbidity burden and risk of second primary non-breast cancer in breast cancer survivors.

Background: Breast cancer survivors have an increased risk of second primary cancers. However, the impact of comorbidity burden on risk of second primary non-breast cancer in breast cancer survivors is under-studied. We evaluated the association of comorbidity burden with risk of second primary non-breast cancer in breast cancer survivors.

Persistent prescription opioid use and all-cause mortality following the first-year breast cancer survivorship.

Background: Harm associated with persistent opioid use beyond the first-year intensive cancer treatment is underinvestigated in cancer survivors. We examined rates and risk factors for persistent opioid use and all-cause mortality after the first-year breast cancer survivorship.

Methods: This retrospective cohort study used electronic health record data from Kaiser Permanente Southern California for women diagnosed with a nonmetastatic breast cancer between 2009 and 2019 who filled 2 or more opioid prescriptions.

Population attributable risk of a competing-risk model for breast cancer and non-breast cancer death among women ≥ 65 years.

Purpose: To inform decision making around mammography-screening frequency and cessation, we previously used Fine-Gray competing-risk regression to develop and validate a model to estimate older women's 10-year risk of breast cancer and their competing risk of non-breast cancer (non-BC) death. Here, we aimed to understand the amount of incident breast cancer and non-BC death risk explained by our model among women ≥ 65y.

Methods: We included women ≥ 65y who completed the 2004 Nurses' Health Study questionnaire (NHS, n = 59,662) or who participated in the Women's Health Initiative-Extension Study (WHI-ES, n = 82,528).

Intentional Weight Loss, Waist Circumference Reduction, and Mortality Risk Among Postmenopausal Women.

Importance: Research investigating weight loss and mortality risk often fails to differentiate between intentional and unintentional weight loss and typically uses body mass index (BMI) as the measure of excess body weight.

Objective: To evaluate associations between weight loss and waist circumference (WC) reduction and mortality, considering weight loss intentionality.

Design, Setting, And Participants: This cohort study used data from the Women's Health Initiative Observational Study, which had a prospective cohort with mean follow-up of 18.

MGMT epimutations and risk of incident cancer of the colon, glioblastoma multiforme, and diffuse large B cell lymphomas.

Background: Constitutional BRCA1 epimutations (promoter hypermethylation) are associated with an elevated risk of triple-negative breast cancer and high-grade serous ovarian cancer. While MGMT epimutations are frequent in colon cancer, glioblastoma, and B-cell lymphoma, it remains unknown whether constitutional MGMT epimutations are associated with risk of any of these malignancies.

Methods: We designed a nested case-control study, assessing potential associations between MGMT epimutations in blood from healthy individuals and subsequent risk of incident cancer.

Breast Cancer Risk Assessment Tool (BCRAT) and long-term breast cancer mortality in the Women's Health Initiative.

Background: While the Breast Cancer Risk Assessment Tool (BCRAT) predicts breast cancer incidence, the model's performance, re-purposed to predict breast cancer mortality, is uncertain. Therefore, we examined whether the BCRAT model predicts breast cancer mortality in postmenopausal women in the Women's Health Initiative (WHI).

Methods: BCRAT 5-year breast cancer incidence risk estimates were calculated for 145,408 women (aged 50-79 years) enrolled in the WHI at 40 US clinical centers to examine associations of BCRAT risk groups (< 1%, 1-< 3%, ≥ 3%) with breast cancer mortality using Cox proportional regression modeling in all participants and in those with incident breast cancer.

Menopausal Hormone Therapy and Ovarian and Endometrial Cancers: Long-Term Follow-Up of the Women's Health Initiative Randomized Trials.

Purpose: Menopausal hormone therapy's influence on ovarian and endometrial cancers remains unsettled. Therefore, we assessed the long-term influence of conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) and CEE-alone on ovarian and endometrial cancer incidence and mortality in the Women's Health Initiative randomized, placebo-controlled clinical trials.

Materials And Methods: Postmenopausal women, age 50-79 years, were entered on two randomized clinical trials evaluating different menopausal hormone therapy regimens.

Estrogen Plus Progestin and Colorectal Cancer: Long-Term Findings From the Women's Health Initiative Randomized Clinical Trial.

JCO We report long-term colorectal cancer findings from the Women's Health Initiative trial where 16,608 postmenopausal women with a uterus were randomly assigned to daily conjugated equine estrogen (CEE) 0.625 mg, plus medroxyprogesterone acetate (MPA) 2.5 mg, or placebo.

Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women's Health Initiative.

Background: In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials.

Methods: A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population.

Ductal carcinoma in situ and cause-specific mortality among younger and older postmenopausal women: the Women's Health Initiative.

Background: Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women's Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years).

Methods: Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls.

The Women's Health Initiative Randomized Trials and Clinical Practice: A Review.

Importance: Approximately 55 million people in the US and approximately 1.1 billion people worldwide are postmenopausal women. To inform clinical practice about the health effects of menopausal hormone therapy, calcium plus vitamin D supplementation, and a low-fat dietary pattern, the Women's Health Initiative (WHI) enrolled 161 808 postmenopausal US women (N = 68 132 in the clinical trials) aged 50 to 79 years at baseline from 1993 to 1998, and followed them up for up to 20 years.

Randomized trials of estrogen-alone and breast cancer incidence: a meta-analysis.

Purpose: In the Women's Health initiative (WHI) randomized clinical trial, conjugated equine estrogen (CEE)-alone significantly reduced breast cancer incidence (P = 0.005). As cohort studies had opposite findings, other randomized clinical trials were identified to conduct a meta-analysis of estrogen-alone influence on breast cancer incidence.

Dietary Intervention Favorably Influences Physical Functioning: The Women's Health Initiative Randomized Dietary Modification Trial.

Background: In the Women's Health Initiative Dietary Modification randomized trial, the dietary intervention reduced breast cancer mortality by 21% (P = .02) and increased physical activity as well.

Objective: Therefore, the aim was to examine whether or not these lifestyle changes attenuated age-related physical functioning decline.

Long-term breast cancer incidence trends by mammography, obesity, and menopausal hormone therapy.

Purpose: Over the past half century, the annual age-adjusted breast cancer incidence in the USA has fluctuated, potentially influenced by changes in mammography screening, obesity, and menopausal hormone therapy. As the relative contributions of these factors on breast cancer incidence have not been resolved, we assembled reliable sources of year-to-year changes in mammography, obesity, and hormone therapy to graphically display their relationship to breast cancer incidence through 50 years.

Methods: Year-to-year trends were assembled: for mammography from the Center for Disease Control National Health Interviews; for hormone therapy from the Collaborative Group on Hormonal Factors in Breast Cancer report; for obesity from the NCD (Non-Communicable Diseases) Risk Factor Collaboration; and for breast cancer for US women 50-64 years of age from Surveillance, Epidemiology, and End Results (SEER) registry findings.

Validating a model for predicting breast cancer and nonbreast cancer death in women aged 55 years and older.

Background: To support mammography screening decision making, we developed a competing-risk model to estimate 5-year breast cancer risk and 10-year nonbreast cancer death for women aged 55 years and older using Nurses' Health Study data and examined model performance in the Black Women's Health Study (BWHS). Here, we examine model performance in predicting 10-year outcomes in the BWHS, Women's Health Initiative-Extension Study (WHI-ES), and Multiethnic Cohort (MEC) and compare model performance to existing breast cancer prediction models.

Methods: We used competing-risk regression and Royston and Altman methods for validating survival models to calculate our model's calibration and discrimination (C index) in BWHS (n = 17 380), WHI-ES (n = 106 894), and MEC (n = 49 668).

Changes in physical function in older women with endometrial cancer with or without adjuvant therapy.

Objective: To evaluate changes in physical function (PF) for older women with endometrial cancer (EC) + / - adjuvant therapy in the Women's Health Initiative Life and Longevity after Cancer cohort.

Materials And Methods: This study examined women ≥ 70 years of age with EC with available treatment records. Change in PF was measured using the RAND-36 and compared between groups using Wilcoxon rank-sum tests.

Risk of Subsequent Breast Cancer in Women with Early Stage HER2-Positive Breast Cancer in a Large Community Health Plan.

Purpose: Clinical outcomes have improved for women with early stage, HER2-positive breast cancer following the FDA approval of adjuvant trastuzumab use in 2006. However, only limited information exists on such patients' outcomes in real-world settings outside of clinical trials. We examined the risk of subsequent breast cancer in women with HER-2 positive disease, and the impact of trastuzumab use, in a large California community-based health plan.

Menopausal hormone therapy and change in physical activity in the Women's Health Initiative hormone therapy clinical trials.

Objective: The menopausal transition results in a progressive decrease in circulating estrogen levels. Experimental evidence in rodents has indicated that estrogen depletion leads to a reduction of energy expenditure and physical activity. It is unclear whether treatment with estrogen therapy increases physical activity level in postmenopausal women.

Predicting All-Cause Mortality in Women With and Without Breast Cancer Using the Schonberg Index: A Women's Health Initiative Study.

Background: When treating older women with breast cancer, life expectancy is an important consideration. ASCO recommends calculating 10-year mortality probabilities to inform treatment decisions. One useful tool is the Schonberg index, which predicts risk-based all-cause 10-year mortality.

Metabolomics-Based Biomarker for Dietary Fat and Associations with Chronic Disease Risk in Postmenopausal Women.

Background: The Women's Health Initiative (WHI) randomized, controlled Dietary Modification (DM) trial of a low-fat dietary pattern suggested intervention benefits related to breast cancer, coronary heart disease (CHD), and diabetes. Here, we use WHI observational data for further insight into the chronic disease implications of adopting this type of low-fat dietary pattern.

Objectives: We aimed to use our earlier work on metabolomics-based biomarkers of carbohydrate and protein to develop a fat intake biomarker by subtraction, to use the resulting biomarker to develop calibration equations that adjusts self-reported fat intake for measurement error, and to study associations of biomarker-calibrated fat intake with chronic disease risk in WHI cohorts.

Metabolomics Biomarkers for Fatty Acid Intake and Biomarker-Calibrated Fatty Acid Associations with Chronic Disease Risk in Postmenopausal Women.

Background: A substantial observational literature relating specific fatty acid classes to chronic disease risk may be limited by its reliance on self-reported dietary data.

Objectives: We aimed to develop biomarkers for saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acid densities, and to study their associations with cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) in Women's Health Initiative (WHI) cohorts.

Methods: Biomarker equations were based primarily on serum and urine metabolomics profiles from an embedded WHI human feeding study (n = 153).