Pathologic response in er-low early-stage breast cancer treated with neoadjuvant pembrolizumab plus chemotherapy

Keywords

ER-low - breast cancer - immunotherapy - pathologic response

Background: Estrogen receptor-low (ER-low) breast cancer (BC) exhibits a tumor biology more similar to basal-like tumors than to luminal-like tumors. Despite patients with ER-low breast cancer having been excluded from the Keynote-522 study, they were included in trials evaluating neoadjuvant pembrolizumab (Keynote-526 trial) and nivolumab (CheckMate 7FL) for hormone receptor-positive BC. Although the ER-low subgroup was small, a benefit from neoadjuvant immunotherapy was suggested, with pathologic complete response (pCR) rates of 55.9% and 55.6% in the immunotherapy arms compared to 30.2% and 28.6% in the control arms, respectively.

Objective: To evaluate the outcomes of ER-low BC treated with neoadjuvant P+CT.

Methods: The real-world data (RWD) Neo-Real/GBECAM 0123 study is collecting data on patients with BC treated with neoadjuvant P+CT since July 2020 across ten Brazilian cancer institutions. In this analysis, we evaluated the clinical characteristics and efficacy outcomes of patients with ER-low BC, focusing on the rates of pCR and residual cancer burden (RCB) 0-1. ER-low was defined as estrogen receptor expression lower than 10% in immunohistochemistry.

Results: Among 410 patients included in this cohort to date, 14 had ER-low BC; 9 (64.3%) had stage II and 5 (35.7%) had stage III disease. The median age was 39.7 years (range 28 - 61). The majority of patients had grade 3 tumors (n = 13, 92.8%), and the median Ki67 index was 77% (range 30% - 90%). Thirteen patients completed the neoadjuvant therapy and underwent surgery. Among these, 8 (61.5%) achieved a pCR. The RCB 0-1 rate was also 61.5%; all five patients (38.5%) who did not achieve a pCR had RCB 2. Among 325 patients with ER-negative BC included in the same RWD study who had already undergone surgery, the pCR rate was 62.1%. With a median follow-up of 15.6 months, one patient in the ER-low group with residual disease had a recurrence. No recurrence was observed among the ER-low patients with a pCR.

Conclusion: In this cohort, ER-low BC represented a small subgroup enriched by tumors of high grade and high proliferative index. The pCR rates with neoadjuvant P+CT were comparable to those observed in TNBC. These results support the use of neoadjuvant immunotherapy for the ER-low subgroup.

Corresponding author: Renata Rodrigues da Cunha Colombo Bonadio (e-mail: [e-mail]).