DNA-Based Biomarkers as Predictors of Carboplatin Response in Neoadjuvant Treatment for Hormone Receptor Positive and Triple-Negative Breast Cancer.

Authors

Arne V Pladsen, Marianne L Smebye, Øystein Garred, Elin Borgen, Eivind V Egeland, Mads H Haugen, Maria A Dahle, Lina Prasmickaite, Gunhild M Mælandsmo, Eivind Hovig, Sigve Nakken, Alexandra Østgaard, Inger R Bergheim, Kristin Reinertsen, Hege Oma Ohnstad, Ellen Schlichting, Helle K Skjerven, Anne-Lise B Dale, Erik Wist, Bjørn Naume, Hege G Russnes, Ole Christian Lingjærde, Olav Engebraaten

Published in

Clinical cancer research : an official journal of the American Association for Cancer Research. Oct 14, 2026. Epub Oct 14, 2026.

Abstract

This prospective, randomized neoadjuvant study evaluated DNA-based biomarkers to identify breast cancer patients most likely to benefit from carboplatin (Cb). While Cb improves outcomes in triple-negative breast cancer (TNBC), responses vary, and its role in aggressive hormone receptor-positive breast cancer (HR+BC) remains uncertain.
Patients (N = 187) with early, high-risk, HER2-negative cT2-4 tumors received 12 weekly paclitaxel with or without Cb, followed by four cycles of epirubicin and cyclophosphamide. Pretreatment tumor whole-exome sequencing was used to calculate the complex arm-wise aberration index (CAAI), loss of heterozygosity (LOH) fraction, and homologous recombination deficiency (HRD) status.
For TNBC patients, pathologic complete response (pCR) was obtained in 69% (24/35) with Cb versus 43% (16/37) with control (p = 0.036) whereas 74% (26/35) and 65% (24/37), respectively, acquired either pCR or recidual cancer burden class 1 (RCB 1; p = 0.45). Cb significantly prolonged event-free survival (EFS; p = 0.017). In patients with a low genomic LOH fraction, Cb improved EFS (p = 0.007). Low genomic LOH fraction also indicated an unfavourable prognosis without Cb, confirmed in an independent cohort (n = 67, p = 0.02). For HR+BC patients, pCR was 15% (9/60) with Cb versus 11% (6/55) with control (p = 0.59), but the proportion achieving low residual cancer burden (pCR and RCB 1) increased from 16% (9/55) to 35% (21/60; p = 0.033). Among patients having HR+BC tumors with HRD, 5 of 8 attained pCR with Cb compared with 4 of 47 HRD-negative tumors (p = 0.002).
This study indicates distinct predictive values of complex DNA-based biomarker analyses for breast-cancer subtypes. Low genomic LOH fraction may identify TNBC patients who benefit most from Cb, while HRD may guide Cb use in HR+BC.

PMID:
42870529
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.

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