Faculty Bibliography

BACKGROUND:) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology. METHODS:We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy. RESULTS:The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO. CONCLUSION/CONCLUSIONS:The BMI breast cancer HRs remained less than or near one during the 45-55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.

BACKGROUND:The incidence of differentiated thyroid cancer (DTC) is higher in women than in men but whether sex steroid hormones contribute to this difference remains unclear. Studies of reproductive and hormonal factors and thyroid cancer risk have provided inconsistent results. METHODS:Original data from 1 252 907 women in 16 cohorts in North America, Europe, Australia and Asia were combined to evaluate associations of DTC risk with reproductive and hormonal factors. Multivariable-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS:During follow-up, 2142 women were diagnosed with DTC. Factors associated with higher risk of DTC included younger age at menarche (<10 vs 10-11 years; HR, 1.28; 95% CI, 1.00-1.64), younger (<40; HR, 1.31; 95% CI, 1.05-1.62) and older (≥55; HR, 1.33; 95% CI, 1.05-1.68) ages at menopause (vs 40-44 years), ever use of menopausal hormone therapy (HR, 1.16; 95% CI, 1.02-1.33) and previous hysterectomy (HR, 1.25; 95% CI, 1.13-1.39) or bilateral oophorectomy (HR, 1.14; 95% CI, 1.00-1.29). Factors associated with lower risk included longer-term use (≥5 vs <5 years) of oral contraceptives (HR, 0.86; 95% CI, 0.76-0.96) among those who ever used oral contraception and baseline post-menopausal status (HR, 0.82; 95% CI, 0.70-0.96). No associations were observed for parity, duration of menopausal hormone therapy use or lifetime number of reproductive years or ovulatory cycles. CONCLUSIONS:Our study provides some evidence linking reproductive and hormonal factors with risk of DTC. Results should be interpreted cautiously considering the modest strength of the associations and potential for exposure misclassification and detection bias. Prospective studies of pre-diagnostic circulating sex steroid hormone measurements and DTC risk may provide additional insight.

INTRODUCTION/BACKGROUND:Evidence is limited on the role of mid-life Dietary Approaches to Stop Hypertension (DASH) diet in late-life subjective cognitive complaints (SCCs). METHODS:We included 5116 women (mean age in 1985-1991: 46 years) from the New York University Women's Health Study. SCCs were assessed from 2018 to 2020 (mean age: 79 years) by a 6-item questionnaire. RESULTS:Compared to women in the bottom quartile of the DASH scores, the odds ratio (OR) for having two or more SCCs was 0.83 (95% confidence interval: 0.70-0.99) for women in the top quartile of DASH scores at baseline (P for trend = 0.019). The association was similar with multiple imputation and inverse probability weighting to account for potential selection bias. The inverse association was stronger in women without a history of cancer (P for interaction = 0.003). DISCUSSION/CONCLUSIONS:Greater adherence to the DASH diet in mid-life was associated with lower prevalence of late-life SCCs in women.

PURPOSE/OBJECTIVE:There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS:We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS: CONCLUSION/CONCLUSIONS:This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

OBJECTIVE:To evaluate the association between census-tract level measures of social vulnerability and residential segregation and IPN follow up. METHODS:This retrospective cohort study included patients with IPN ≥6 mm in size or multiple subsolid/ground-glass IPNs <6 mm (with non-optional follow-up recommendations) diagnosed between January 1, 2018 and December 30, 2019 at a large urban tertiary center and followed ≥two years. Geographic sociodemographic context was characterized by 2018 U.S. Centers for Disease Control and Prevention Social Vulnerability Index (SVI) and the Index of Concentration at the Extreme (ICE), categorized in quartiles. Multivariable binomial regression models were utilized with a primary outcome of inappropriate IPN follow up (late or no follow up). Models were also stratified by nodule risk. RESULTS:The study consisted of 2,492 patients (mean age 65.6 years +/- 12.6 years; 1,361 women). Top-quartile SVI patients were more likely to have inappropriate follow up (Risk Ratio [RR]: 1.24, 95% Confidence Interval [95% CI], 1.12-1.36]), compared with the bottom quartile; risk was also elevated in top-quartile SVI subcategories of Socioeconomic Status (RR: 1.23, 95% CI, 1.13-1.34), Minority Status and Language (RR: 1.24, 95% CI, 1.03-1.48), Housing and Transportation (RR: 1.13, 95% CI, 1.02-1.26), and ICE (RR: 1.20, 95% CI, 1.11-1.30). Further, top-quartile ICE was associated with greater risk of inappropriate follow up among high-risk vs. lower-risk IPN (1.33 [1.18-1.50] vs. 1.13 [1.02-1.25]), respectively, P for interaction= 0.017). DISCUSSION/CONCLUSIONS:Local social vulnerability and residential segregation are associated with inappropriate IPN follow up and may inform policy or interventions tailored for neighborhoods.

BACKGROUND:Living in neighborhoods with higher levels of walkability has been associated with a reduced risk of obesity and higher levels of physical activity. Obesity has been linked to increased risk of 13 cancers in women. However, long-term prospective studies of neighborhood walkability and risk for obesity-related cancer are scarce. OBJECTIVES:We evaluated the association between long-term average neighborhood walkability and obesity-related cancer risk in women. METHODS:The New York University Women's Health Study (NYUWHS) is a prospective cohort with 14,274 women recruited between 1985 and 1991 in New York City and followed over nearly three decades. We geocoded residential addresses for each participant throughout follow-up and calculated an average annual measure of neighborhood walkability across years of follow-up using data on population density and accessibility to destinations associated with geocoded residential addresses. We used ICD-9 codes to characterize first primary obesity-related cancers and employed Cox proportional hazards models to assess the association between average neighborhood walkability and risk of overall and site-specific obesity-related cancers. RESULTS: DISCUSSION:Our study highlights a potential protective role of neighborhood walkability in preventing obesity-related cancers in women. https://doi.org/10.1289/EHP11538.

STUDY OBJECTIVES/OBJECTIVE:Obstructive sleep apnea (OSA) has been associated with more severe acute coronavirus disease-2019 (COVID-19) outcomes. We assessed OSA as a potential risk factor for Post-Acute Sequelae of SARS-CoV-2 (PASC). METHODS:We assessed the impact of preexisting OSA on the risk for probable PASC in adults and children using electronic health record data from multiple research networks. Three research networks within the REsearching COVID to Enhance Recovery initiative (PCORnet Adult, PCORnet Pediatric, and the National COVID Cohort Collaborative [N3C]) employed a harmonized analytic approach to examine the risk of probable PASC in COVID-19-positive patients with and without a diagnosis of OSA prior to pandemic onset. Unadjusted odds ratios (ORs) were calculated as well as ORs adjusted for age group, sex, race/ethnicity, hospitalization status, obesity, and preexisting comorbidities. RESULTS:Across networks, the unadjusted OR for probable PASC associated with a preexisting OSA diagnosis in adults and children ranged from 1.41 to 3.93. Adjusted analyses found an attenuated association that remained significant among adults only. Multiple sensitivity analyses with expanded inclusion criteria and covariates yielded results consistent with the primary analysis. CONCLUSIONS:Adults with preexisting OSA were found to have significantly elevated odds of probable PASC. This finding was consistent across data sources, approaches for identifying COVID-19-positive patients, and definitions of PASC. Patients with OSA may be at elevated risk for PASC after SARS-CoV-2 infection and should be monitored for post-acute sequelae.

Detecting and characterizing subgroups with differential effects of a binary treatment has been widely studied and led to improvements in patient outcomes and population risk management. Under the setting of a continuous treatment, however, such investigations remain scarce. We propose a semiparametric change-plane model and consequently a doubly robust test statistic for assessing the existence of two subgroups with differential treatment effects under a continuous treatment. The proposed testing procedure is valid when either the baseline function for the covariate effects or the generalized propensity score function for the continuous treatment is correctly specified. The asymptotic distributions of the test statistic under the null and local alternative hypotheses are established. When the null hypothesis of no subgroup is rejected, the change-plane parameters that define the subgroups can be estimated. This paper provides a unified framework of the change-plane method to handle various types of outcomes, including the exponential family of distributions and time-to-event outcomes. Additional extensions with nonparametric estimation approaches are also provided. We evaluate the performance of our proposed methods through extensive simulation studies under various scenarios. An application to the Health Effects of Arsenic Longitudinal Study with a continuous environmental exposure of arsenic is presented. This article is protected by copyright. All rights reserved.