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Purpose: Fracture and osteoporosis are known side effects of aromatase inhibitors (AIs) for postmenopausal hormone receptor positive (HR+) breast cancer (BC) patients. How modifiable lifestyle factors impact fracture risk in these patients is relatively unknown. Methods: We conducted a prospective cohort study to examine the association of lifestyle factors, focusing on physical activity, with risk of incident major osteoporotic fracture and osteoporosis in 2152 HR+ BC patients diagnosed from 2006 to 2013 at Kaiser Permanente Northern California and who received AIs. Patients self-reported lifestyle factors at study entry and at 6-month follow-up. Fracture and osteoporosis outcomes were prospectively ascertained by physician-adjudication and bone mineral density (BMD) values, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated from multivariable proportional hazards regression. Models were adjusted for age, menopausal status, race/ethnicity, body mass index (BMI), AJCC stage, breast cancer treatment, prior osteoporosis, and prior major fracture. Results: Over a median 6.1 years of follow-up after AI initiation, 165 women experienced an incident osteoporotic fracture and 243 women had osteoporosis. No associations were found between overall moderate-vigorous physical activity and fracture risk, although < 150 min/week of aerobic exercise in the 6 months after BC diagnosis was associated with increased fracture risk (HR=2.42; 95% CI: 1.34, 4.37) compared with ≥ 150 min/week (meeting physical activity guidelines). Risk was also higher for never or infrequently engaging in aerobic exercise (HR=1.90; 95% CI: 1.05, 3.44). None or infrequent overall moderate-vigorous physical activity in the 6 months before BC diagnosis was associated with increased risk of osteoporosis (HR=1.94; 95% CI: 1.11; 3.37). Conclusions: Moderate-vigorous physical activity during the immediate period after BC diagnosis, particularly aerobic exercise, was associated with lower risk of major osteoporotic fractures in women on AI therapy. Implications for cancer survivors: Findings may inform fracture prevention in women on AI therapy through non-pharmacologic lifestyle-based strategies. [ABSTRACT FROM AUTHOR]

Earlier puberty has been associated with numerous adverse mental, emotional, and physical health outcomes. Obesity is a known risk factor for earlier puberty in girls, but research with boys has yielded inconsistent findings. We examined sex- and race/ethnicity-specific associations between childhood obesity and puberty in a multiethnic cohort of 129,824 adolescents born at a Kaiser Permanente Northern California medical facility between 2003 and 2011. We used Weibull regression models to explore associations between childhood obesity and breast development onset (thelarche) in girls, testicular enlargement onset (gonadarche) in boys, and pubic hair development onset (pubarche) in both sexes, adjusting for important confounders. Clear dose-response relationships were observed. Boys with severe obesity had the greatest risk for earlier gonadarche (hazard ratio = 1.23, 95% confidence limit: 1.15, 1.32) and pubarche (hazard ratio = 1.44, 95% confidence limit: 1.34, 1.55), while underweight boys had delayed puberty compared with peers with normal body mass index. A similar dose-response relationship was observed in girls. There were significant interactions between childhood body mass index and race/ethnicity. Childhood obesity is associated with earlier puberty in both boys and girls, and the magnitude of the associations may vary by race/ethnicity. Prevention of childhood obesity may delay pubertal timing and mitigate health risks associated with both conditions. [ABSTRACT FROM AUTHOR]

99 Background: Several studies have shown that older women diagnosed with breast cancer and eligible for chemotherapy treatment are more likely to be dose-reduced than younger women; however, most prior studies were limited by small sample sizes and examined relative dose intensity of a single drug. We assessed the association between age at diagnosis with first cycle dose proportion (FCDP) and average relative dose intensity (ARDI) across multiple regimens in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study. Methods: This retrospective cohort study included 10,386 women ages 18+ years treated with adjuvant chemotherapy for stage I-IIIA breast cancer at Kaiser Permanente Northern California (KPNC) and Washington (KPWA) between 2004-2019. We examined associations between age at diagnosis with first cycle dose proportion (FCDP, defined as <90% of the guideline-recommended dose, reflecting clinician intent at treatment outset) and average relative dose intensity (ARDI, defined as dose proportion <90% across the course of chemotherapy). We used multivariable-adjusted generalized linear models of the Poisson family with a log link-function and robust standard errors to calculate prevalence ratios (PR) and corresponding 95% confidence intervals (CI). We adjusted for patient and tumor characteristics, with and without adjusting for pre-existing comorbidities. Results: The proportion of women with a FCDP <90% ranged from 3% among women ages 18-39 years to 19% among women ages 75+ years. Women ages 75+ years were statistically significantly more likely to have a FCDP <90% and ARDI <90% vs women ages 40-49 years regardless of adjustment for comorbidities (Table). Conclusions: Older age at diagnosis is strongly associated with chemotherapy dose reductions relative to guideline recommendations, both at the outset of chemotherapy initiation and across the course of treatment. Understanding implications of dose reductions on chemotoxicities and survival will be particularly important for improving the quality of care and long-term outcomes for older women. Age at Diagnosis (years) FCDP <90% Multivariable Adjusted* PR (95% CI) FCDP <90% Additionally Adjusted* for Comorbidities PR (95% CI) ARDI <90% Multivariable Adjusted* PR (95% CI) ARDI <90% Additionally Adjusted* for Comorbidities PR (95% CI) 18-39 0.81 (0.53-1.23) 0.84 (0.55-1.29) 0.84 (0.68-1.03) 0.85 (0.69-1.04) 40-49 REF REF REF REF 50-64 1.32 (1.08-1.61) 1.29 (1.06-1.59) 1.16 (1.04-1.29) 1.14 (1.02-1.26) 65-74 1.72 (1.36-2.17) 1.65 (1.29-2.10) 1.34 (1.18-1.52) 1.26 (1.11-1.43) 75+ 4.90 (3.61-6.65) 4.39 (3.16-6.09) 1.94 (1.61-2.35) 1.75 (1.44-2.13) p-trend <0.001 <0.001 <0.001 <0.001 *Adjusted for BMI, stage at diagnosis, year of diagnosis, study site, race/ethnicity, income, body mass index, human epidermal growth factor receptor status, grade, nodal number, estrogen and progesterone receptor status. [ABSTRACT FROM AUTHOR]

421 Background: Social support is important to the management of breast cancer treatment. Our team has developed data from electronic health record (EHR) data into structured 'concept groups' that will form the basis for the development of EHRsupport, a computable, EHR-based measure of social support. We report the evaluation of these concept groups against chart review as a part of our validation. Methods: We built a natural language processing (NLP) algorithm on clinical notes in 7,989 women diagnosed from January 2006 to September 2021 with invasive breast cancer. We identified and developed 10 concept groups from unstructured data: 1) living situation, 2) marital/partner status, 3) parenthood status, 4) visit support (accompanied patient to ≥1 visit, patient attended alone at ≥1 visit), 5) friends/other support, 6) explicit positive or negative mentions of social support, 7) mention of a deceased person, 8) transportation issues, 9) relationship conflict or stress, and 10) social isolation. We validated concept groups against the charts of 100 patients randomly drawn from the broader patient population (nonoverlapping with the training data set) also around the time (-1 to +3 months) of diagnosis. Results: Concept group data availability ranged from 1.3% social isolation to 98.3% for living situation. Specificity and negative predictive values were moderate to high for all concept groups. Sensitivity and positive predictive values were moderate to high for concept groups with high data availability (Table) and lower for concept groups with low data availability. Conclusions: Data on social support have been available since the advent of Epic in 2006 and our NLP-based algorithm accurately captured data within the EHR that were systematically collected supporting the development of a clinical tool that can be used to identify patients at risk of low social support. EHRsupport concept groups, data availability (n=7,989), and evaluation vs. chart review. Availability (%) Sensitivity Specificity PPV NPV Living situation (e.g., alone or not) 98.3 100 92 61 100 Partner/spouse 92.0 85 100 100 81 Parenthood status 88.8 95 80 93 83 Visit support 82.9 92 77 96 59 Positive mentions social support *46.9 75 100 100 70 Negative mentions social support 33 99 67 96 Friend/other support 46.8 81 81 79 83 Deceased person 39.9 86 97 95 90 Transportation issues 14.6 80 85 22 99 Relationship conflict/stress 7.7 25 95 29 94 *Availability of positive and negative mentions of social support. [ABSTRACT FROM AUTHOR]

326 Background: Vaccines protect cancer patients from developing severe illness, hospitalization, and death. At Kaiser Permanente (KP) South Sacramento Medical Center (KPSSC), oncology patients on active chemotherapy had an overall flu vaccination rate of 13% between September 1, 2022, and December 1, 2022. Our aim was to increase this rate to 33% during the 2023 flu season. Methods: In conjunction with the ASCO Quality Training Program, we applied quality improvement initiatives to improve flu vaccination. Our population of interest included adult cancer patients on active chemotherapy at KPSCC. We evaluated the barriers to vaccination assessment by distributing surveys to infusion nurses. We performed three Plan-Do-Study-Act (PDSA) cycles for quality improvement and monitored flu vaccination rates. Cycle 1 (9/11/2023 to 11/5/2023): We distributed the ASCO flu vaccine handout at oncology clinic. We had medical assistants and infusion nurses administer flu vaccines during clinic visits and chemotherapy sessions. Cycle 2 (11/6/2023 to 11/21/2023): We added the vaccine handout in Chinese and Spanish and updated our receptionists' script to strongly encourage patients to receive flu vaccine. Cycle 3 (11/22/2023 to 12/6/2023): KP flu clinic set up an onsite flu vaccine cart one half day per week in the oncology clinic. Results: Barriers to vaccination assessment in the clinic included lack of time (60%), difficulty remembering to ask (10%), and non-influenza season (10%). Our interventions resulted in an increased flu vaccination rate from 13% in 2022 to 36% in 2023. During cycle 1, 298 out of 615 patients received their vaccine (48.5%). During cycle 2, 16 out of 118 patients received their vaccine (13.6%). PDSA cycle 3 resulted in 14 out of 178 patients receiving their vaccine (7.9%). Conclusions: Promoting vaccine awareness via active engagement with nurses and medical assistants early on and having onsite vaccine availability in the oncology clinic were keys to improve the overall flu vaccination rate. While most vaccines were administered at the beginning of flu season, the addition of language-tailored vaccine handouts and having an onsite vaccine cart towards the end of the season did result in late season vaccinations. Our findings do support the importance of providing timely vaccine information in the oncology clinic. Our future goal is to expand these efforts to other KP Northern California oncology centers to establish stable onsite vaccine availability in clinics and include additional vaccine types. [ABSTRACT FROM AUTHOR]

310 Background: Little is known about how provider and facility factors relate to patients' receipt of dose-reduced adjuvant chemotherapy. Methods: In a cohort of 8,581 stage I-IIIA women with breast cancer treated with chemotherapy at Kaiser Permanente Northern California between 2006 and 2019, we evaluated the associations between provider- and facility-level factors related to chemotherapy dosing with a primary interest in the first cycle dose reduction (FCDR). Here, FCDR is defined as a first cycle dose proportion <90% of that expected based on the intended regimen, reflecting clinician intent at the outset of chemotherapy. Provider-level factors examined included provider gender, age, race, Hispanic ethnicity, years since completion of medical school, volume of breast cancer patients treated per year, and patient-provider racial concordance; we also examined practice size and rurality. Prevalence ratios (PR) were calculated using generalized linear models of the Poisson family with a log-link function and robust standard errors, accounting for significant patient factors and clustering at the provider level. Results were further mutually-adjusted for significant provider- and facility-level factors to ensure independence of associations. Results: Patients treated by providers practicing for longer (30+ years since medical school vs <10 years) were more likely to be dose-reduced at the outset of chemotherapy (PR: 1.94; 95% CI: 1.15-3.25; p-trend: 0.02). Patients treated by providers in a larger practice (10+ vs ≤5 oncologists) were less likely to be dose reduced (PR: 0.53; 95% CI: 0.34-0.84; p-trend: 0.03) as were patients treated by providers treating a higher volume of breast cancer patients (30+ vs ≤15 patients/year: PR 0.64 (95% CI: 0.41-0.99; p-trend: 0.03). Other factors examined were not significantly associated with use of FCDR. Conclusions: These results indicate provider years of experience, as well as practice size and the volume of breast cancer patients treated per year are significantly associated with first cycle dose reductions in chemotherapy. This is a complex, multi-factorial issue, and these results indicate that provider- and provider- and facility-level factors should be considered when evaluating sources of heterogeneity in chemotherapy delivery. [ABSTRACT FROM AUTHOR]