Clustering Molecular Subtypes in Breast Cancer, Immunohistochemical Parameters and Risk of Axillary Nodal Involvement.

(1) Background: To establish similarities in the risk of axillary lymph node metastasis between different groups of women with breast cancer according to immunohistochemical (IHC) parameters. (2) Methods: Data was collected retrospectively, from 2000 to 2013, of 1058 node-positive breast tumours. All patients were divided according to the St Gallen 2013 criteria and IHC features. The proportion of axillary involvement (pN > pN0; pN > pN1mi; pN > pN1) was calculated for each group. Similarities in axillary nodal dissemination were explored by cluster analysis and association between IHC and risk of axillary disease was studied with multivariate analysis. (3) Results: Among clinico-pathological surrogates of intrinsic subtypes, axillary involvement was more frequent in Luminal-B like HER2 negative (45.8%) and less frequent in Luminal-B HER2 positive (33.8%; p = 0.044). Axillary macroscopic involvement was more frequent in Luminal-B like HER2 negative (37.9%) and HER2 positive (37.8%) and less frequent in Luminal-B HER2 positive (25.5%) and Luminal-A like (25.6%; p = 0.002). Axillary involvement ≥pN2 was significantly less frequent in Luminal-A like (7.4%; p < 0.001). Luminal-A with Luminal-B HER2 positive, and triple-negative with Erb-B2 overexpressing tumours were clustered together regarding any axillary involvement, macroscopic disease or ≥pN2. Among the defined subgroups, axillary metastases were more frequent when Ki67 was higher. In a multivariate analysis, Ki67>14% were associated with a risk of axillary metastases (HR: 1.31; 95% CI, 1.51−6.80; p < 0.037). (4) Conclusions: there are two lymphatic drainage pathways of the breast according to the expression of hormone receptor-related genes. Positive-ER tumors are associated with lower axillary involvement and negative-ER tumors and Ki67 > 14% with higher nodal involvement.