Endocrine therapy non-adherence and recurrence risk in patients with breast cancer and major depressive disorder.

10595 Background: We evaluated whether non-adherence to oral endocrine therapy explains the increased hazard of recurrence among women with major depressive disorder (MDD) and estrogen receptor-positive breast cancer. Methods: We established a retrospective cohort of veteran women (age ≥18 years), with and without MDD, diagnosed with early-stage invasive estrogen receptor-positive breast cancer between 2010-2019 within the United States Veterans Affairs Healthcare System with follow-up through 2022. We assessed adherence to oral endocrine therapy among continuous users (no treatment gaps ≥ 6 months) over two-years (N = 2,722) and five-years (N = 1,666). Adherence was measured using the proportion of medication days covered and evaluated across thresholds from ≥20%-100%. We used multivariable competing-risks regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the statistical interaction between MDD and endocrine therapy adherence on breast cancer recurrence, adjusting for sociodemographic, clinical, and prognostic factors. Results: The hazard of breast cancer recurrence significantly differed between adherent and non-adherent women with MDD beginning at adherence thresholds of ≥60% over two-years and ≥40% over five-years. At these minimal adherence thresholds, breast cancer recurrence was higher for women with MDD who were non-adherent to endocrine therapy over two-years (HR = 1.65; 95% CI = 1.02-2.62) and five-years (HR = 2.10; 95% CI = 1.16-3.79) compared with adherent women without MDD. In contrast, women with MDD who remained adherent over two-years (HR = 1.21; 95% CI = 0.91-1.64) and five-years (HR = 1.38; 95% CI = 0.85-2.22) had hazards of breast cancer recurrence comparable to those of adherent women without MDD. Conclusions: Our findings identify endocrine therapy adherence as a potentially modifiable clinical factor to reduce breast cancer recurrence among women with MDD and estrogen receptor-positive disease.