Axillary surgery solely to guide CDK4/6 inhibitor eligibility in early breast cancer

Evidence before this study

We systematically searched PubMed, MEDLINE, Embase, and major oncology conference proceedings for publications between Jan 1, 2010, and June 30, 2025. We included randomised and large prospective studies that investigated oncologic outcomes after omitting sentinel lymph node biopsy (SLNB) or completion axillary lymph node dissection (cALND), or that assessed the efficacy and safety of adjuvant CDK4/6 inhibitors in hormone receptor-positive, HER2-negative early breast cancer. The SOUND, INSEMA, and SENOMAC trials consistently showed that omitting SLNB or cALND in patients with clinically node-negative or limited node-positive disease does not compromise invasive disease-free survival, distant disease-free survival, or overall survival, while markedly reducing the risk of arm morbidity and lymphoedema. In contrast, the monarchE and NATALEE trials showed that adjuvant abemaciclib and ribociclib improve invasive disease-free survival and distant disease-free survival in high-risk populations, although these benefits come at the cost of frequent grade 3 or worse adverse events in roughly half of treated patients. However, the implications of less extensive axillary surgery for CDK4/6 inhibitor eligibility, and the balance between potential benefit, harm, and health-care costs, had not been examined previously.

Added value of this study

This analysis combines data from five major randomised trials to quantify the trade-offs between axillary surgery, CDK4/6 inhibitor use, treatment-related morbidity, and cost. We introduce the number needed to diagnose and treat as a new measure linking surgical staging with systemic therapy outcomes. Our results indicate that performing SLNB or cALND solely to determine eligibility for CDK4/6 inhibition requires very high number needed to diagnose and treat (106–807), adds substantial morbidity, and is costly, with only marginal overall survival benefit.

Implications of all the available evidence

The totality of current evidence supports omission of SLNB or cALND in appropriately selected low-risk patients with early breast cancer. Performing axillary surgery solely to guide eligibility for adjuvant CDK4/6 inhibitors does not seem warranted. Future strategies should focus on alternative diagnostic strategies to identify patients who truly benefit from treatment escalation, while reducing unnecessary harm and health-care expenditure.

Source: The Lancet Oncology