Reclassifying contralateral axillary metastasis: survival benefit of aggressive local therapy challenges stage IV...

Contralateral axillary metastasis (CAM) is currently staged as M1 (stage IV) breast cancer, guiding treatment towards palliative systemic therapy. However, emerging evidence suggests CAM may behave as a locoregional event, potentially amenable to curative-intent strategies. This study aims to define the prognosis of isolated CAM and evaluate the survival impact of aggressive local therapy.

We conducted a retrospective cohort study of 1110 patients from two tertiary centers, comprising three cohorts: CAM (n=128), stage IIIC locally advanced breast cancer (LABC, n=532), and de novo oligometastatic (M1, n=450) disease. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox regression. Within the CAM cohort, we employed propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and multivariable Cox models to compare outcomes between patients receiving curative-intent local therapy (surgery/radiotherapy) versus a systemic therapy-focused approach.

The adjusted mortality risk for the CAM cohort was significantly lower than for the M1 cohort (aHR 0.58, 95% CI 0.45-0.74) but higher than for the LABC cohort (aHR 1.18, 95% CI 0.93-1.60). In the PSM analysis, curative-intent therapy was associated with a 51% reduction in mortality risk (HR 0.49, 95% CI 0.31-0.78) and a significantly lower 5-year cumulative incidence of locoregional recurrence (12.1% vs. 31.4%, p=0.005). Results were consistent across IPTW and multivariable analyses.

Patients with isolated CAM exhibit a prognosis distinct from classic stage IV disease. A curative-intent local treatment strategy is independently associated with significantly improved survival and locoregional control, supporting the re-evaluation of CAM as a clinically regionally treatable entity.