Avoiding Chemotherapy in ER-Positive, Node-Positive Breast Cancer

The prior TAILORx trial (NEJM JW Oncol Hematol Jul 2018 and N Engl J Med 2018; 379:111) showed that 21-gene recurrence score (RS) intermediate results (11–25) could be used to identify patients with estrogen-receptor (ER)-positive, node-negative breast cancer who could avoid adjuvant chemotherapy without any detrimental impact on outcome. Now, to provide similar guidance for patients with ER-positive, node-positive disease, investigators conducted a prospective, multicenter, randomized trial (RxPONDER), sponsored by the National Cancer Institute Cancer Therapy Evaluation Program.

The trial involved 5018 women (67% postmenopausal) from 632 sites in nine countries with ER-positive and HER2-negative, early-stage breast cancer with 1 to 3 involved axillary lymph nodes and an RS of ≤25. Participants were assigned to endocrine therapy with or without chemotherapy. Stratification factors included RS (0–13 or 14–25), menopausal status, and type of axillary surgery (sentinel-node biopsy or axillary lymph-node dissection).

Results at a median follow-up of 5 years were as follows:

• Among postmenopausal women, invasive disease-free survival (iDFS; the primary objective) was similar with endocrine-only therapy or chemo-endocrine therapy (91.9% and 91.3%, respectively); no subgroup gained benefit from chemotherapy.
• Among premenopausal women, iDFS was improved with chemo-endocrine therapy versus endocrine-only therapy (93.9% vs. 89.0%; hazard ratio, 0.60; P=0.002)
• No chemotherapy benefit was observed in premenopausal women age ≥50 years; those age <50 years did achieve a benefit (HR, 0.48).
• The chemotherapy benefit for premenopausal women remained significant (HR, 0.60), after adjustment for age, number of positive nodes, tumor grade, and tumor size; the benefit did not increase as RS increased.