To investigate predictors of treatment interruption and early discontinuation of adjuvant hormonal therapy (HT) in a retrospective cohort of women with newly diagnosed hormone receptor-positive (HR +) breast cancer. Eligible cases were identified from a single institutional tumor registry from 2009 to 2015. Patients were followed from initiation of adjuvant HT for a minimum of one year through December 1, 2016. Predictors of treatment interruption or early discontinuation were analyzed with Cox proportional hazards regression models. With a median follow-up time of 3.0 years (IQR 1.5–4.5), 22 women (10.9%) discontinued HT early and 47 (23.4%) had at least one treatment interruption of > 14 days. Adjusted Cox proportional hazards regression models showed that women with pre-existing affective disorders were more likely to discontinue therapy early (HR 3.15; 95% CI 1.35–7.37), while those with pre-existing chronic pain disorders were at increased risk for treatment interruption (HR 2.24; 95% CI 1.20–4.19). HT-related symptoms were the most commonly reported reason for HT interruption or discontinuation. Women who experienced severe treatment-related symptoms were at increased risk for both HT interruption (HR 2.64; 95% CI 1.07–6.50) and HT discontinuation (HR 3.48; 95% CI 1.20–10.1). This study showed that HT interruptions and discontinuation were common, often associated with HT-related symptoms. Clinicians caring for breast cancer patients on HT should monitor closely for treatment-emergent symptoms, especially women with pre-existing disorders, and support them to continue therapy through aggressive symptom management and other patient-centered approaches.