Background: Although randomized controlled trials (RCTs) provide evidence of efficacy, generalization of these results to patients in the real-world setting is challenging, given RCTs are conducted in highly selected patient populations. An understanding of the effectiveness and safety of approved cancer therapies in routine clinical practice is essential in order to optimize the management of these patients and to identify treatment and safety gaps. Treat ER⁺ight is the first Canadian study to describe real-world treatment patterns/sequencing, effectiveness and safety for postmenopausal HR⁺HER2^- advanced breast cancer (aBC) patients. Methods: This registry incorporates an observational prospective cohort design and will enroll 320 postmenopausal HR⁺HER2^- aBC women that have been previously exposed to non-steroidal aromatase inhibitor (NSAI) therapy being treated with: endocrine therapy (ET) alone or ET in combination with targeted therapy (ET+TT). Patients who are receiving chemotherapy, have had > 3 lines of systemic treatment in the advanced setting or are participating in a randomized investigational trial will be excluded. All treatments, assessments and follow-up will be according to the treating physician’s judgment and practice, independent of the study; however, data collection schedule is as follows: ET+TT cohort: weeks 2, 4, 12 and every 12 weeks thereafter and ET cohort: 4 weeks and every 12 weeks thereafter. Once ET/ET+TT is terminated (for any reason), data is collected every 12 weeks up to 1 year. A subgroup of patients enrolled at select sites will undergo serial blood collections for ctDNA analysis as part of an optional exploratory biomarker sub-study. Outcome measures include treatment duration, adherence and sequence, prevention and management of treatment emergent adverse events, health care resource utilization, patient reported health-related quality-of-life (EORTC QLQ-C30 and – BR23), work-related productivity and survival status.