Are all high-grade breast cancers with no steroid receptor hormone expression alike? The special case of the medullary phenotype

Background: Medullary carcinoma (MC) of the breast is associated with favorable prognosis compared with other histological types, despite high nuclear grade, fast proliferation and lack of steroid hormone receptor expression. We retrospectively evaluated the clinical relevance of selected immunohistochemical features of tumors in three cohorts of patients with typical medullary (MC), ‘atypical’ medullary (AMC) or ductal (DC) breast carcinoma. Patients and methods: Evaluation was performed on node-negative tumor specimens from 40 patients who had either MC (12 patients), AMC (nine patients) or DC (19 patients), treated in a single institution. All had no hormonal receptor, Ki-67 30%, G3, expansive pattern of growth and peritumoral lymphocytic infiltration. In addition, p27, p21 and HER2/neu overexpression, p53, cyclin E and E-cadherin expression, presence of apoptotic cells, stromal tenascin (TN), and type of immune cell infiltration (CD3- and CD68-positive cells) were assessed. Results: No difference in expression of HER2/neu, p21, p27, p53, number of apoptotic cells and CD68-positive cells was detected. Lower levels of stromal TN expression were found in MC compared with DC (P=0.0007), but differences between MC and AMC were not significant (P=0.27). A higher proportion of intratumoral CD3-positive cells was seen in MC than in AMC (P=0.046). No differences were seen between MC and DC (P=0.73). With a median follow-up of 67 months, three patients with DC had relapsed in distant sites, while one patient with AMC had a second primary. Two patients with MC had reappearance of DC in the breast. Conclusions: The three distinct disease types, selected by having similar high proliferation, had similar expression of cell cycle regulators. The lower expression of TN and massive infiltration of T lymphocytes might both indicate a special interaction between tumor cells and microenvironment, important features for conferring improved prognosis through negligible invasive and metastatic potential to MC. In our series, however, patients with a previous MC are not free from the risk of developing a subsequent DC. Finally, defining AMC as a distinct entity from DC is not justified.