The Absolute Effect / Evidence / Breast Cancer
RxPONDER (SWOG S1007)
Clinical question: In HR-positive/HER2-negative breast cancer with one to three positive nodes and a 21-gene recurrence score ≤25, can genomic testing identify patients who can omit adjuvant chemotherapy?
Registry: NCT01272037 · One underlying study; aliases and follow-up publications consolidated.
Design, population and eligibility
Phase III, randomized trial
5,018 randomized patients; approximately 4,984 in the primary efficacy analysis. Premenopausal and postmenopausal women with 1–3 positive nodes and recurrence score 0–25.
HR-positive/HER2-negative invasive breast cancer, one to three positive axillary nodes, 21-gene recurrence score 0–25. Patients with more than three positive nodes or recurrence score >25 were not represented in the randomized question.
Follow-up and endpoint maturity are stated with the reported efficacy results; further long-term updates are noted where applicable.
Treatment and comparator
Endocrine therapy alone versus chemotherapy followed by endocrine therapy. Chemotherapy was taxane- and/or anthracycline-based at investigator discretion; regimen was not uniform.
Primary and secondary endpoints
Primary endpoint: invasive disease-free survival (iDFS). Secondary endpoints included distant disease-free survival and overall survival; menopausal status was a prespecified stratification factor.
Key efficacy results
At 5 years, overall iDFS was 92.2% with chemoendocrine therapy versus 91.0% with endocrine therapy alone; overall HR 0.86 (95% CI 0.72–1.03; P=0.10).
Premenopausal: 5-year iDFS 93.9% versus 89.0%; HR 0.60 (95% CI 0.43–0.83; P=0.002); distant DFS HR 0.58 (95% CI 0.39–0.87; P=0.009). Postmenopausal: 91.3% versus 91.9%; HR 1.02 (95% CI 0.82–1.26; P=0.89).
Source-reported outcome visualization
Five-year iDFS by menopausal status.
The chemotherapy benefit differed by menopausal status. Do not pool these groups into one treatment recommendation.
Absolute effect
Premenopausal patients: 5-year iDFS absolute difference 4.9 percentage points (93.9% vs 89.0%); approximate NNT 21 for one additional patient free of an iDFS event at 5 years. Postmenopausal patients had no benefit (91.3% vs 91.9%; HR 1.02); no NNT is assigned. These are fixed-time estimates.
Trial-specific toxicity and treatment burden
Chemotherapy adds acute and late toxicity, including myelosuppression, febrile neutropenia, alopecia, nausea, neuropathy, fatigue, ovarian failure/infertility and rare cardiotoxicity or secondary malignancy, depending on regimen. Because chemotherapy choice was investigator-selected, regimen-specific grade 3–5 rates should not be collapsed into one universal toxicity figure. The trial did not test ovarian suppression plus endocrine therapy as a substitute for chemotherapy.
Quality of life and patient-reported outcomes
Patient-reported outcomes and treatment burden must be considered alongside the menopausal interaction. Avoiding chemotherapy can spare acute toxicity in postmenopausal patients with RS 0–25; in premenopausal patients, chemotherapy-associated ovarian suppression may contribute to observed benefit.
Subgroups and applicability
The prespecified menopausal interaction is central. In premenopausal patients, benefit was observed across recurrence-score range 0–25 and did not rise with higher score. The chemotherapy effect may partly reflect ovarian function suppression; RxPONDER did not randomize ovarian suppression against chemotherapy.
Current-practice context · reviewed 3 November 2026
For postmenopausal patients with HR-positive/HER2-negative disease, 1–3 positive nodes and RS 0–25, chemotherapy can generally be omitted based on RxPONDER. In premenopausal patients, chemotherapy benefit was observed and decisions require discussion of ovarian suppression, fertility and recurrence risk. Do not extrapolate to >3 nodes or RS >25.
Limitations and critical interpretation
The chemotherapy regimens were heterogeneous. Menopausal status is a clinical surrogate for ovarian function; the mechanism of benefit in premenopausal women is unresolved. The study does not prove ovarian suppression is equivalent to chemotherapy.
Bottom line: RxPONDER is a biomarker-guided treatment-selection landmark: a low 21-gene score supports chemotherapy omission in postmenopausal node-positive patients, but not routinely in premenopausal patients.
Primary sources and follow-up publications
Outcome values are sourced from the linked reports. Unreported values are not imputed. NNT/NNH is only stated when an explicit fixed-time absolute difference supports a defensible calculation; no NNT is derived from median survival.