Background: With the increased utilization of molecular gene signatures, clinicians have identified a population of breast cancer patients that have clinically advanced disease associated with a low risk molecular profile. This discordance between tumor stage and molecular prognosis results in a dilemma for which consensus and evidence to guide treatment decisions are lacking. The I-SPY 2 Low Risk Registry (LRR) was therefore developed to capture the critical treatment data and clinicopathologic outcomes of these patients. A correlative biomarker study to characterize the biology and heterogeneity amongst these tumors is also planned. The goals of the LRR are to observe treatment patterns, determine tumor chemoendocrine sensitivity, and monitor clinical outcomes of these patients in order to inform the development of future studies aimed to optimize their management and outcomes.
Methods: Patients with stage II or III breast cancer are recruited from the ongoing phase 2 neoadjuvant I-SPY 2 TRIAL. In this study, patients with Hormone Receptor-positive, HER2-negative disease are not eligible to be randomized to standard chemotherapy and a novel agent if their tumor has a 70-gene good-prognosis signature; instead, they are encouraged to enroll in the LRR. Treatment on the LRR is not pre-specified and at the discretion of the oncology team and patient. Data collection includes: screening MRI and tumor biospecimen, surgical pathology, menopause status, treatment administered, quality of life assessment, recurrence events and survival. Follow up for 15 years is planned. Biomarker analyses will include, but are not limited to, Ki-67, SET Index, GREB1, and HOXB13:IL17BR ratio. As of January 2015, 156 patients across 20 sites were eligible for the LRR, and 72 have enrolled to the Low Risk Registry. Clinical trial information: NCT01042379.