Title: Limiting systemic endocrine overtreatment in postmenopausal breast cancer patients with an ultralow classification of the 70-gene signature

Publication: Breast Cancer Res Treat. 2022; 194(2): 265–278

Authors: Opdam, et al.

Purpose
Guidelines recommend endocrine treatment for estrogen receptor-positive (ER+) breast cancers for up to 10 years. Earlier data suggest that the 70-gene signature (MammaPrint) has potential to select patients that have an excellent survival without chemotherapy and limited or no tamoxifen treatment. The aim was to validate the 70-gene signature ultralow-risk classification for endocrine therapy decision making.

Methods
In the IKA trial, postmenopausal patients with non-metastatic breast cancer had been randomized between no or limited adjuvant tamoxifen treatment without receiving chemotherapy. For this secondary analysis, FFPE tumor material was obtained of ER+HER2− patients with 0–3 positive lymph nodes and tested for the 70-gene signature. Distant recurrence-free interval (DRFI) long-term follow-up data were collected. Kaplan–Meier curves were used to estimate DRFI, stratified by lymph node status, for the three predefined 70-gene signature risk groups.

Results
A reliable 70-gene signature could be obtained for 135 patients. Of the node-negative and node-positive patients, respectively, 20% and 13% had an ultralow-risk classification. No DRFI events were observed for node-negative patients with an ultralow-risk score in the first 10 years. The 10-year DRFI was 90% and 66% in the low-risk (but not ultralow) and high-risk classified node-negative patients, respectively.

Conclusion
These survival analyses indicate that the postmenopausal node-negative ER+HER2− patients with an ultralow-risk 70-gene signature score have an excellent 10-year DRFI after surgery with a median of 1 year of endocrine treatment. This is in line with published results of the STO-3-randomized clinical trial and supports the concept that it is possible to reduce the duration of endocrine treatment in selected patients.