DNA-Based Biomarkers as Predictors of Carboplatin Response in Neoadjuvant Treatment for Hormone Receptor Positive and Triple-Negative Breast Cancer
In brief
Carboplatin raised complete response from 43% to 69% in triple-negative breast cancer
In this 187-patient randomized study, carboplatin increased complete responses in triple-negative breast cancer, and patients with low genomic loss of heterozygosity had better event-free survival with the drug. In hormone receptor-positive disease, 5 of 8 tumors with homologous recombination deficiency had a complete response, versus 4 of 47 without it; these small biomarker subgroups need validation.
- Journal
- Clinical cancer research : an official journal of the American Association for Cancer Research (Q1)
- Published
- 14 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Arne V Pladsen, Marianne L Smebye, Øystein Garred, Elin Borgen, Eivind V Egeland, Mads H Haugen, et al.
- PMID
- 42870529
- DOI
- 10.1158/1078-0432.CCR-26-2212
Why clinicians should know about it
- Picked for Oncology and Radiation Oncology (paper of the day, 16 October 2026): DNA biomarkers identify carboplatin responders in breast cancer
Abstract
PURPOSE: 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 AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.