RxPONDER.

Top Line: Does the 21-gene recurrence score (RS) predict the benefit of chemo in women with node positive breast cancer?

The Study: The RS is a mainstay in the treatment of early stage breast cancer by helping determine which patients derive benefit from adjuvant chemotherapy. And while the RS has been shown to be predictive of chemo benefit in node positive patients, this hasn’t been tested in a prospective randomized trial. In RxPONDER, women with hormone receptor positive, HER2-negative breast cancer and 1-3 positive nodes were eligible for enrollment and underwent RS testing. Over 5000 women who had a RS of 0-25 were randomized to receive chemoendocrine therapy or endocrine therapy alone. Those with a RS >25 received chemoendocrine therapy. The goal was to determine if there was a difference in invasive DFS and if there was an interaction between continuous RS and DFS. At 5 years, there was no difference in invasive DFS between chemoendocrine therapy (92.2%) and endocrine therapy (91%). While an increasing RS was prognostic of shorter invasive DFS, it was not predictive of the relative benefit of chemoendocrine therapy on invasive DFS. What was predictive of chemo benefit? Menopausal status and age. In premenopausal women, chemoendocrine therapy improved 5 year invasive DFS from 89→ 93.9%, and all subgroups benefited from chemotherapy. However, it was premenopausal women under 50 who derived the benefit from chemo. In postmenopausal women, there was no benefit even among subgroups. In closing, the authors ponder whether the cytotoxic effects of chemo or the chemo-induced menopause/ovarian suppression drive the benefit seen among premenopausal women. 

TBL: In women with HR+, HER2- breast cancer with 1-3 positive nodes, the 21-gene RS  in the range of 0-25 is not predictive of chemotherapy benefit. Premenopausal women with a RS of 0-25 have improved 5 year invasive DFS with chemoendocrine therapy regardless of RS, whereas postmenopausal women with a RS of 0-25 do not. | Kalinsky, New Engl J Med 2021