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Background Patient-reported outcomes (PROs) can provide valuable information about drug benefit-risk tradeoffs from the patient perspective and are particularly important to patients with breast cancer due to its symptoms and adverse events from breast cancer treatments. The United States Food and Drug Administration (U.S. FDA) has acknowledged PROs as important approval endpoints used in clinical trials of cancer drugs. However, previous studies found that PROs are rarely mentioned in cancer drug labels, a widely used and trusted source of information about drugs. Our objectives were to compare PRO data reported in FDA labeling versus FDA medical review documents for breast cancer drugs approved in the U.S. between 2000 and 2019 to identify possible causes for PRO-data labeling exclusions. Methods We included new molecular entities (NMEs) and biologic license applications (BLAs) initially approved for breast cancer treatment by the FDA between 1/1/2000 and 12/31/2019. Product labeling and FDA medical review documents were collected from the FDA-Approved Drugs database (Drugs@FDA). From these resources, details on PRO measures used in trials, design of trials using PRO measures, PRO-endpoint status, analytical methods, and FDA reviewer comments regarding PRO measurement were extracted. Results Of 633 FDA-approved drugs, 13 were indicated for breast cancer treatment; none of their prescribing information contained information about PROs. However, 11 of 13 (85%) included PRO measures and endpoint information in FDA medical review documents. PRO measures were used in 14 different clinical trials, and FDA reviewers’ comments regarding PRO measurement were related to lack of meaningfulness and clinical significance, lack of content validity, and inadequate analytical methods. Conclusions Despite the importance of PROs to patients with breast cancer, PRO measures were only described in FDA medical review documents of breast cancer drugs, but not in drug product labeling. Therefore, it appears that PRO data are often collected in breast cancer trials, but have not been methodologically acceptable to FDA reviewers. Collaborative efforts between the FDA and industry are warranted to increase the number of breast cancer drug applications with appropriate use of PRO measures and endpoints.

Prescription drug spending and other financial factors (e.g., out-of-pocket costs) partially explain variation in cost-related medication nonadherence (CRN). Indicators of social capital such as neighborhood factors and social support may influence the health and well-being of older adults as they may rely on community resources and support from family and peers to manage conditions. Previous research on the relationship of social capital and CRN has limited evidence and contradictory findings. Hence, our objective is to assess the relationship of social capital indicators (neighborhood social cohesion, neighborhood physical disorder, positive social support, and negative social support) and CRN using a longitudinal design, 2006 to 2016, in a nationally representative sample of older adults in the United States (US). The Health and Retirement Study is a prospective panel study of US adults aged ≥ 50 years evaluated every two years. Data was pooled to create three waves and fitted using Generalized Estimating Equation modelling adjusting for both baseline and timevarying covariates (age, sex, education, race, total household income, and perceived health status). The three waves consisted of 11,791, 12,336, and 9,491 participants. Higher levels of neighborhood social cohesion and positive social support were related with lower CRN (OR 0.92, 95% CI 0.88-0.95 and OR 0.77, 95% CI 0.70-0.84, p<0.01). In contrast, higher levels of neighborhood physical disorder and negative social support were related to higher CRN (OR 1.07, 95% CI 1.03-1.11 and OR 1.46, 95% CI 1.32-1.62, p<0.01). Interventions targeting social capital are needed, reinforcing positive social support and neighborhood social cohesion and diminishing neighborhood physical disorder and negative social support for older adults.

Background: In several recent studies of postmenopausal women, the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with lower circulating estrogens. These analgesics have also been studied in association with breast cancer risks with inconsistent findings. Cross-talk between immune and endocrine factors may play important roles in the development of breast cancer. Methods: We conducted a study of postmenopausal women drawn from the Prostate, Lung, Colon and Ovarian Cancer Screening Trial cohort (PLCO). At study baseline, participants reported their frequency of use for aspirin, non-aspirin NSAIDs via questionnaire. High-performance liquid chromatography-tandem mass spectrometry was used to measure estrogens and estrogen metabolites (EM) in baseline serum samples from 354 women who went on to get breast cancer during study follow-up, and 423 women who remained healthy. All selected participants reported no use of menopausal hormones at study baseline. General linear models were used to estimate multivariable-adjusted mean EM by self-reported use of analgesics (daily, weekly, or less than weekly) in all participants, while adjusting for continuous age, baseline BMI and breast cancer outcome. Results: In comparison to women who reported that they did not use any NSAIDs on a daily basis, those reporting daily use of aspirin only, daily use of non-aspirin NSAIDs only and daily use of both aspirin and non-aspirin NSAIDs had lower multivariable adjusted serum concentrations of unconjugated estradiol (Pdiff<0.02). Greater frequency of non-aspirin NSAID use was associated with trends towards lower concentrations of total EM (Ptrend=.004), estrone (Ptrend=.004), and unconjugated estradiol (Ptrend=.04), and higher ratios of 2- and 4- hydroxylated EM to the parent estrogens (Ptrend=.02 and .04). Associations were similar in women who did and did not go on to have breast cancer. Discussion: In this sample of postmenopausal women, more frequent use of NSAIDs was associated with lower circulating estrogens and with patterns of estrogen metabolism that may be more favorable with respect to breast cancer risk. These results require independent confirmation in additional well-designed studies. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.