Pathological complete response, histologic grade, and level of stromal tumor-infiltrating lymphocytes in ER + HER2- breast cancer.

Background: Recent trials have integrated immune checkpoint inhibitors (ICIs) into neoadjuvant chemotherapy (NAC) in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer of histologic grade (HG) III. We assessed the pathological complete response (pCR) rate according to the level of stromal tumor-infiltrating lymphocytes (sTIL) and HG in patients with ER + HER2- breast cancer undergoing NAC.

Methods: Between January 2016 and December 2023, we retrospectively identified 376 patients with ER + HER2- breast cancer who underwent NAC followed by surgery. HG and sTIL levels were examined in the biopsied samples before NAC. Multiple sTIL cutoff values as 10%, 20%, and 30% were applied.

Results: Twenty-seven patients (7.2%) had HG III tumors. The pCR rate in the HG III group was 22.2%, which was significantly higher than that in the HG I/II group (4.0%) (p < 0.001). The HG III group had a higher mean sTIL level than HG I/II group (38.7% vs. 12.9%; p < 0.001). According to the sTIL levels, the pCR rate in the high sTIL group was significantly higher than that in the low sTIL group: i) cutoff of 10%, 2.4% vs. 9.5%; cutoff of 20%, 2.8% vs. 13.7%; and cutoff of 30%, 3.2% vs. 18.3%. In the high sTIL (≥ 30%) group, the pCR rate for HG III was 33.3%, whereas that for HG I/II was 13.3%.

Conclusions: High tumor grade and sTIL levels were associated with higher rates of pCR in ER + HER2- breast cancer. Our findings support that the addition to ICIs to NAC increased pCR in high-risk, HG III, ER + HER2- breast cancer and suggest that sTIL levels could be utilized to identify patients with ER + HER2- breast cancer eligible for chemoimmunotherapy.