Association Between the Number of Invasive Tumor Foci and Axillary Nodal Burden in Multifocal and Multicentric Breast Cancer

Multifocal and multicentric (MF/MC) breast cancers are associated with increased axillary lymph node involvement, but the relevance of the number of invasive tumor foci is less clear. This retrospective study included 1087 patients with non-metastatic invasive breast cancer who underwent definitive surgery between 2010 and 2022 without prior neoadjuvant therapy. Patients were grouped as having one, two, or three or more invasive foci; the three-or-more-foci category was used pragmatically to avoid small subgroups at higher focus counts rather than as a data-derived threshold. Multivariable logistic and Cox regression analyses were used to evaluate advanced nodal disease (N2/N3) and disease-free survival (DFS), respectively. N2/N3 disease was present in 18.4%, 19.0%, and 38.2% of patients, respectively (p < 0.001). Three or more foci were independently associated with N2/N3 disease (OR 2.81, 95% CI 1.65–4.79; p < 0.001), whereas two foci were not. At a median follow-up of 113.1 months, 10-year DFS rates were 77.0%, 82.5%, and 55.7%, respectively (log-rank p = 0.003). Three or more foci remained associated with poorer DFS after multivariable adjustment (HR 1.58, 95% CI 1.07–2.33; p = 0.022), whereas two foci were not. A statistically significant difference in OS was not demonstrated (log-rank p = 0.088), although the study may have had limited power for this endpoint. Greater nodal burden and poorer DFS were mainly observed in patients with three or more invasive foci. Focus number may help characterize this heterogeneity within MF/MC disease, although its value beyond total invasive tumor burden remains uncertain.