Defining lymphocyte-predominant breast cancer by the proportion of lymphocyte-rich stroma and its significance in routine histopathological diagnosis.

Lymphocyte-predominant breast cancer (LPBC) defined by the density of stromal lymphocytes shows favorable behavior. However, considerable distribution heterogeneity of lymphocytes is a major problem. The present study defined LPBC by the proportion of lymphocyte-rich stroma with the cut-off values of 30, 50, and 75%, and clinicopathologically analyzed mainly LPBC (area > 30%) defined by the cut-off value of 30%. LPBCs (area > 30%), 39 cases in total, were composed mainly of triple-negative and HER2(+) /ER(-) subtypes, without any luminal A-like subtype. LPBCs were composed predominantly of histological grade 3 tumors, without any grade 1 lesions. Multivariate analyses on 477 consecutive tumors revealed that ER-negativity and grade 3 status associated significantly with LPBC. LPBC (area > 30%) showed better disease-free survival than grade-matched controls, and it was a good indicator of complete pathological remission after pre-operative chemotherapy. Patients with LPBC with the cut-off value of 50% and that of 75% showed 100% disease-free survival. These results demonstrated the validity of our definition of LPBC. Our data also suggest that de-differentiated cancers without TILs could be regarded as high-grade cancer without lymphocyte-mediated responses. In conclusion, the definition of LPBC by the proportion of lymphoid stroma is useful for prognostication of high grade breast cancer in routine diagnosis.