The impact of menopausal status on the efficacy of adjuvant CDK4/6 inhibitors in hormone receptor-positive early breast cancer: a systematic review and meta-analysis of phase III clinical trials
In brief
Adjuvant CDK4/6 inhibitors lower recurrence risk by roughly 20% in both pre- and post-menopausal patients
A meta-analysis of four phase-III trials (17,748 women) found invasive disease-free survival improved about 20% with CDK4/6 inhibitors in both pre-/peri-menopausal (HR 0.80) and postmenopausal (HR 0.79) groups, with no significant difference between them. Overall survival showed no clear benefit, and greater outcome variability in pre-menopausal women suggests endocrine-therapy differences may still matter.
- Journal
- Breast cancer research and treatment (Q1)
- Published
- 13 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Uri Bender, Karine Ronan, Amal Aljuhani, Jacqueline Savill, Eitan Amir
- PMID
- 42593586
- DOI
- 10.1007/s10549-026-08056-7
Why clinicians should know about it
- Picked for Breast and Endocrine Surgery (top studies of the week, 16 August 2026): Meta‑analysis of adjuvant CDK4/6 inhibitors in early breast cancer
- Picked for Dermatology (top studies of the week, 16 August 2026): Menopausal status on adjuvant CDK4/6 inhibitors in breast cancer
- Picked for Oncology and Radiation Oncology (top studies of the week, 16 August 2026): Menopausal status does not affect adjuvant CDK4/6 inhibitor efficacy
Abstract
PURPOSE: Adjuvant cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve outcomes in hormone receptor-positive (HR+), HER2-negative early breast cancer, though trial results have been heterogeneous. Menopausal status and endocrine therapy backbone may contribute to variability in treatment effect. We performed a meta-analysis evaluating whether menopausal status influences the efficacy of adjuvant CDK 4/6 inhibition. METHODS: A systematic review of phase III randomized trials evaluating adjuvant CDK4/6i in HR+/HER2- early-stage breast cancer was conducted. Trial-level hazard ratios (HRs) and 95% confidence intervals (CIs) for iDFS and OS were extracted separately for pre-/peri-menopausal and postmenopausal subgroups. HRs were pooled using random-effects modelling (DerSimonian-Laird method) with inverse-variance modeling. Heterogeneity was assessed using I² statistics. A sensitivity analysis limited to approved CDK4/6i (ribociclib and abemaciclib) was performed. RESULTS: Four trials comprising 17,748 participants were included, of whom 45% were pre-/peri-menopausal and 55% were postmenopausal. Pooled iDFS HRs were 0.80 (95% CI 0.67-0.97, I²=64%) in pre-/peri-menopausal patients and 0.79 (95% CI 0.72-0.86, I²=0%) in postmenopausal patients. Pooled OS HRs were 1.02 (95% CI 0.67-1.54, I²=80%) in pre-/peri-menopausal and 0.89 (95% CI 0.78-1.03, I²=0%) in postmenopausal patients. No significant subgroup differences were observed for iDFS or OS. Compared to post-menopausal participants, those who were premenopausal had 3.0% fewer absolute iDFS events at 5-6 years. Sensitivity analyses yielded consistent findings. CONCLUSIONS: Efficacy of adjuvant CDK4/6 inhibition in HR+/HER2-negative early breast cancer does not appear to be influenced by menopausal status as defined in individual trials. Greater heterogeneity among pre-/peri-menopausal patients may reflect differences in endocrine therapy backbone, tumor characteristics and patient risk. CLINICAL TRIAL NUMBER: Not applicable.
Abstract as published, via PubMed.
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