Triple-positive breast carcinoma: Histopathologic features and response to neoadjuvant chemotherapy

Context.-It is unclear whether HER2^þ tumors expressing both estrogen receptor (ER) and progesterone receptor (PR), that is, triple-positive breast carcinomas (TPBCs), show unique morphologic and clinical features and response to neoadjuvant chemotherapy (NAC). Objective.-To study the morphologic and immunohistochemical features of TPBCs from patients who underwent NAC. Design.-We retrospectively reviewed core biopsy and post-NAC slides of 85 TPBCs. H-scores were calculated for ER and PR. HER2 slides and fluorescence in situ hybridization (FISH) reports were reviewed. Residual cancer burden was calculated for post-NAC specimens. Results.-Eighty-one of the 85 tumors (95.3%) showed ductal histology, 3 (3.5%) were invasive lobular carcinomas, and 1 (1.2%) showed mixed ductal and lobular features. A subset showed mucinous (n¼7, 8.2%), apocrine (n ¼ 5, 5.9%), and/or micropapillary (n ¼ 4, 4.7%) differentiation. Fifty-four TPBCs (63.5%) showed high ER expression (H-score.200), including 27 (31.8%) with high expression of ER and PR. Fifty-two tumors (61.1%) showed HER2 3þ staining. Mean HER2/CEP17 ratio by FISH was 3.6 (range, 2-12.2) and mean HER2 signals per cell was 8 (range, 3.7-30.4). Pathologic complete response (pCR) rate was 35.3% (30 of 85). HER2 3þ staining was the only significant predictor of pCR on multivariate analysis (odds ratio ¼ 9.215; 95% CI, 2.401-35.371; P,.001). The ER/PR expression did not correlate with response to therapy. Conclusions.-TPBCs are heterogeneous with some showing mucinous, lobular, or micropapillary differentiation. The pCR rate of TPBCs is similar to that reported for ER^þ/PR-/ HER2^þ tumors. HER2 overexpression by IHC was associated with significantly better response to therapy and may help select patients for treatment in the neoadjuvant setting.