Long-term outcomes of eribulin‑based neoadjuvant chemotherapy for triple‑negative breast cancer patients stratified by homologous recombination deficiency status: results of the randomized JBCRG-22 study

Breast Cancer Res Treat. 2026 Mar 19;216(3):31. doi: 10.1007/s10549-026-07917-5.

Abstract

Purpose: To investigate long-term outcomes for triple‑negative breast cancer (TNBC) patients enrolled in JBCRG-22.

Methods: TNBC (cT1c-T3, cN0-1, M0) patients were stratified by homologous recombination deficiency (HRD) and germline BRCA mutation (gBRCAm) status. Group A patients (aged < 65 years with HRD-positive tumors, or those with gBRCAm, if available) were randomized to receive 4 cycles of weekly paclitaxel (group A1) or eribulin (group A2), both with carboplatin, followed by 4 cycles of anthracycline. Group B patients (aged < 65 years with HRD-negative tumors or aged ≥ 65 years) were randomized to receive 6 cycles of eribulin plus cyclophosphamide (group B1) or eribulin plus capecitabine (group B2). Five-year invasive disease-free survival (IDFS), distant disease-free survival (DDFS), and overall survival (OS) were assessed. Additionally, data were analyzed by biomarker levels including lymphocyte count (LC) and neutrophil-to-lymphocyte ratio (NLR).

Results: Ninety-nine patients were followed for a median of 5.6 years. In patients who received eribulin-based therapy (groups A2 + B1 + B2), 5-year IDFS and OS rates, respectively, were 95% and 100% in patients who achieved pCR after neoadjuvant therapy (n = 20) and 71.4% and 80.2% in those who did not (n = 56), showing significantly better prognosis in the pCR cohort (p < 0.05). OS tended to be better in patients with baseline LC ≥ 1500/mm3 and NLR < 3, particularly in eribulin-treated patients, although differences were non-significant.

Conclusions: These findings will help guide the development of eribulin-based neoadjuvant chemotherapy for selected TNBC patients. Our exploratory analysis of LC and NLR results may help inform clinical prediction models for eribulin-treated patients.

Trial registration: The study has been registered with the University Hospital Medical Information Network Clinical Trials Registry ( https://www.umin.ac.jp/ctr/index-j.htm ) with unique trial number UMIN000023162. The Japan Breast Cancer Research Group trial number is JBCRG-22.

Keywords: BRCA1/2; Eribulin; Homologous recombination deficiency; Immune microenvironment; Neoadjuvant chemotherapy; Triple-negative breast cancer.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Biomarkers, Tumor
  • Female
  • Furans* / administration & dosage
  • Furans* / adverse effects
  • Homologous Recombination*
  • Humans
  • Ketones* / administration & dosage
  • Ketones* / adverse effects
  • Middle Aged
  • Neoadjuvant Therapy / adverse effects
  • Neoadjuvant Therapy / methods
  • Neoplasm Staging
  • Polyether Polyketides / administration & dosage
  • Polyether Polyketides / adverse effects
  • Treatment Outcome
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / mortality
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • eribulin
  • Furans
  • Ketones
  • Polyether Polyketides