Triple-Positive Breast Carcinoma: Histopathologic Features and Response to Neoadjuvant Chemotherapy

It is unclear whether HER2+ 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).

To study the morphologic and immunohistochemical features of TPBCs from patients who underwent NAC.

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.

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 (n = 7, 8.2%), apocrine (n = 5, 5.9%), and/or micropapillary (n = 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 3+ 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 3+ staining was the only significant predictor of pCR on multivariate analysis (odds ratio = 9.215; 95% CI, 2.401-35.371; P < .001). The ER/PR expression did not correlate with response to therapy.

TPBCs are heterogeneous with some showing mucinous, lobular, or micropapillary differentiation. The pCR rate of TPBCs is similar to that reported for ER+/PR-/HER2+ tumors. HER2 overexpression by IHC was associated with significantly better response to therapy and may help select patients for treatment in the neoadjuvant setting.