Abstract Purpose: Clinical guidelines recommend that for women ≥65 years with stage T1N0 breast cancer (BC) treated with breast-conserving surgery (BCS) that breast RT may be omitted and treatment with ET alone is acceptable. However, population-based studies report that up to two-thirds of women with T1N0 BC do not complete 5 years of ET. The effect of non-adherence to ET on recurrence risks in women treated with ET alone is unclear. We established a contemporary population-based cohort of women aged ≥65 years with stage T1N0, hormone receptor positive, breast cancer treated with single modality adjuvant ET or RT alone. We examined the effect of non-adherence in those treated with ET alone and compared the outcomes (ipsilateral LR, any breast event and any invasive in-breast event) of women who were non-adherent to those who were adherent to ET or those treated with RT alone. Methods: A population-based cohort of women diagnosed with T1N0 BC from 2010-2016, aged ≥65 years at diagnosis, treated with BCS and single modality adjuvant therapy with RT alone or ET alone was identified from the Ontario Cancer Registry. ER-/PR-, ER unknown/PR unknown, HER2+ cases and those without sentinel node biopsy or axillary dissection were excluded. Treatment and outcomes were ascertained using deterministic linkages of administrative databases. Receipt of adjuvant ET was identified using dispensing records from the Ontario Drug Benefit Claims database. Adherence percentage at any specific time was calculated by dividing the number of days dispensed (up to that time) by the number of days since diagnosis. This was updated every 3 months for each woman receiving ET. Adherence to ET was captured as a 3-level time-varying covariate (RT only, <80% ET adherence, ≥80% ET adherence). Patients were censored at the time of recurrence. Differences in recurrence risks were compared by Chi-square test. Multivariable Cox regression adjusted for age was used to evaluate risks of ipsilateral LR, any in-breast event (ipsilateral or contralateral, DCIS or invasive) and any first invasive in-breast recurrence. Results: The cohort includes 1551 women; 1054 women treated with BCS + adjuvant RT alone and 497 treated with BCS + adjuvant ET alone. The median follow-up time was 5 years. Almost half (45.7%) of cases prescribed ET alone were <80% adherent. For those who were followed for 5 years, 35% of follow-up time was spent non-adherent to ET. The 5-year risk of LR was 5.8% in patients treated with ET alone who spent <80% of time adherent to ET, 0.4% in patients treated with ET alone who were >80% adherent and 0.9% in those treated with RT alone (p<.001). The 5-year risk of any in-breast event was 6.6% in women <80% adherent, 0.7% in those adherent to ET and 3.2% in those treated with RT alone (p=.001). Women treated with ET alone who were <80% adherent during their follow-up time had a 5-fold increased risk of LR (HR=4.93, 95%CI: 2.13, 11.42, p=0.0002), a 1.6 fold increased risk of any breast event (HR=1.65, 95% CI: 0.89, 3.07, p=0.11) and a 1.6 fold increased risk (HR=1.68, 95% CI: 0.87, 3.25, p=0.13) of any invasive in-breast event compared to those treated with either RT alone or compared to those who were >80% adherent to ET. There was no significant difference in outcomes between those treated with ET who were >80% adherent during their follow-up time and those treated with RT alone. Conclusions: Almost half of women older than 65 years with stage T1N0 breast cancer treated with breast-conserving surgery and adjuvant ET alone are <80% adherent to ET. Non-adherence to ET is associated with higher risks of local recurrence compared to those treated with adjuvant RT alone. Adjuvant approaches incorporating RT may be preferable to ET alone. Citation Format: Mira Goldberg, Rinku Sutradhar, Lawrence Paszat, Timothy Whelan, Sumei Gu, Cindy Fong, Eileen Rakovitch. Non-adherence to endocrine therapy is associated with a significant increased risk of local recurrence in women ≥65 years with stage T1N0 breast cancer treated with adjuvant endocrine therapy alone after breast-conserving surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-06.