Predicting neoadjuvant chemotherapy treatment response in hormone- receptor-positive/HER2-negative breast cancer – results from the Swedish SCAN-B population-based cohort
DOI:
https://doi.org/10.2340/1651-226X.2025.44201Keywords:
Breast cancer, Neoadjuvant chemotherapy, treatment response, pathological complete response, recurrence free survival, Biomarkers, Immunohistochemistry, Gene expression, estrogen receptor status, molecular subtypesAbstract
Background and purpose: Hormone-receptor-positive/HER2-negative (HR+/HER2-) early-stage breast cancers (EBCs) display heterogenous responses to neoadjuvant chemotherapy (NACT) warranting biomarkers to tailor optimal treatment for individual patients.
Patients/material and methods: Women with HR+/HER2- EBC (N = 178) included in the Swedish Sweden Cancerome Analysis Network-Breast (SCAN-B) population-based cohort (2010–2019) treated with NACT were included. We analyzed rates of pathologic complete response (pCR), objective response (OR), breast conserving surgery (BCS), and recurrence-free interval (RFI) in subgroups defined by baseline clinicopathological and molecular characteristics.
Results: The pCR rate was low (6%); nonetheless, after a median follow-up of 5.41 years, all patients who achieved pCR remained recurrence-free despite uniform baseline predicted high PAM50 risk of recurrence (ROR). Younger age (≤ 40 years), cT1, ER% positivity (≤ 66%), and negative PR (≤ 10%) were conventional clinicopathological factors positively associated with increased pCR. Molecular predictors of pCR included negative HR status by gene-expression signatures and non-luminal PAM50 subtypes. Tumor shrinkage ≥ 30%, i.e., OR and BCS, was achieved in 59% and 34%, respectively. No factor was significantly associated with ORR, whereas non-lobular histology and cT1 were positively associated with BCS. In addition, only 1/49 patients who underwent BCS experienced a recurrence during follow-up. Low/intermediate ER% positivity, PR negativity, and non-luminal PAM50 subtype were baseline factors univariately prognostic for inferior long-term outcome in case of residual disease.
Interpretation: Baseline characteristics indicative of reduced hormonal signaling and non-luminal tumor biology assessed more precisely using mRNA profiling can guide optimal tailoring of NACT for patients with high-risk HR+/HER2-tumors. Baseline molecular biology did not predict surgical outcomes following NACT.
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