Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy

Background The benefit of neoadjuvant chemotherapy (NAC) in patients with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancers and in invasive lobular carcinoma (ILC) is uncertain due to the low rates of pathologic complete response (pCR). Objective The aim of this study was to determine if pathologic features can identify subsets likely to benefit from NAC. Methods Patients with stage I–III ER+, HER2− breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs. non-HP). Results From 2007 to 2016, 402 ER+/HER2− cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II–III, and 75% were cN+. Overall pCR rate was 5%; breast pCR in 7% and nodal pCR in 15% of cN+ patients ( p < 0.0001). Patients with ILC initially ineligible for BCS ( n = 56) were less likely to downstage than those with invasive ductal carcinoma (IDC; n = 183, 16 vs. 48%, p ≤ 0.0001), with a similar trend in the axilla ( p = 0.086). The rates of BCS eligibility after NAC were highest in PR−/HP patients (62%) and lowest in PR+/non-HP patients (29%) [ p = 0.005]. In the axilla, nodal pCR among cN+ patients ( n = 301) ranged from 0 to 35% ( p < 0.0001) within these groups, and was most frequent in PR−/HP patients. Conclusions ER+/HER2− patients most likely to benefit from NAC are those with PR− and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared with IDC. The use of these criteria can assist in defining the initial treatment approach.