Josephine Lopes Cardozo, Ph.D. from the Netherlands Cancer Institute speaks about the ASCO 2021 Abstract – Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial.
Link to Abstract:
https://meetinglibrary.asco.org/record/201559/abstract
Backstory:
Gene signatures have been shown to be effective in identifying individuals with a low risk of distant recurrence who might avoid chemotherapy (CT) and are now included in worldwide breast cancer treatment guidelines. Within the low-risk group, an extra threshold was developed for the 70-gene signature (MammaPrint) to identify individuals with an ultralow risk of distant recurrence. These individuals exhibited good breast cancer-specific survival at 15 years in separate cohorts, suggesting that ultralow risk tumors are indolent diseases (Esserman, JAMA Oncol 2017, Delahaye, BC Res Treat 2017). The survival of individuals with an ultralow risk 70-gene profile who took part in the randomized phase 3 MINDACT study is examined here (Piccart, Lancet Oncol 2021).
Methodologies:
Between 2007 and 2011, profiling found an ultralow risk 70-gene profile in 1,000 of the 6,693 patients recruited in the MINDACT study (EORTC 10041/BIG 3-04). (15 percent ). In patients classified by 70-gene signature result (high, low, ultralow), and within the ultralow risk group stratified by clinical risk, we looked at 5- and 8-year distant metastasis-free interval (DMFI) and breast cancer-specific survival (BCSS). We utilized Kaplan-Meier estimates for time to event endpoints and Cox-regression models to compute hazard ratios in these exploratory studies (HR).
Outcomes:
The average period of follow-up was 8.7 years. Among the ultralow risk patients (n = 1,000), 67 percent were under 50 years old, 81 percent had cancers less than 2 cm in diameter, 80 percent had lymph node-negative tumors, 96 percent had grade 1 or 2 tumors, and 99 percent were ER-positive. 83 percent of patients got systemic therapy (69 percent endocrine therapy (ET), 14 percent ET + CT), and 16 percent did not receive any adjuvant systemic treatment (AST). The table shows survival estimates for all endpoints; for ultralow risk, the 8-year DMFI was 97.0 percent (95 percent CI 95.8-98.1). The DMFI was 97.8 percent (95 percent CI 95.3-100) and 97.4 percent (95 percent CI 96.1-98.7) in ultralow risk individuals who got no AST or ET alone. After adjusting for tumor and treatment characteristics, the HR for DMFI was 0.66 (95 percent CI 0.46-0.95) for ultralow vs low risk (preliminary results).
Observations:
Patients with an ultralow risk 70-gene signature had an excellent prognosis in this prospective study, with an 8-year BCSS above 99 percent regardless of clinical risk status and an 8-year DMFI of 95-98 percent.