Abstract 333P
Background
The efficacy and survival data of carboplatin plus taxane neoadjuvant chemotherapy(NAC) in triple-negative breast cancer(TNBC) was lack of a large-sample study. The predictive biomarker of efficacy based on cell-free DNA (cfDNA) whole-methylome sequencing (WMS) has not been reported yet.
Methods
The prospective multi-center cohort study was conducted in four hospitals of China between 2016 and 2023. Stage II-III TNBC patients were enrolled to receive NAC of carboplatin (AUC 5) every 3 weeks or carboplatin (AUC 4) every 2 weeks plus taxane(standard dose) for 4-6 cycles. Plasma samples were prospectively collected at baseline(T1) and after NAC (T2). Chromosomal aneuploidy of featured fragments (CAFF), fragment size index (FSI) and methylation density score (MD) of cfDNA were detected with WMS.
Results
A total of 267 patients were included in the study. The median age was 49 years, 156 patients (58.4%) were stage III disease. 147 patients (55.1%) received the triweekly NAC. 263 patients underwent breast surgery after NAC and 106 patients (40.3%) achieved pCR. The pCR were similar in biweekly or triweekly groups (39.8% vs 40.7%, P=0.89). The 3-year RFS and overall survival (OS) were 77.9%, 87.6%, respectively. Patients who achieved pCR had a significant better RFS (95.5%) and OS (97.7%) than those non-pCR (76.6%, P<0.001; 81.2%, P<0.001). A total of 66 patients with 120 plasma samples (64 samples at T1, 56 samples at T2) were included in WMS analysis. Patients with CAFF, FSI or MD positive at T1 had a higher tumor burden (stage III or cN2-3, all P values <0.05). The proportion of patients with FSI negative at T2 was significantly higher in pCR group compared to non-pCR (86.2% vs 59.3%, P=0.034). There is a similar tendency in patients with CAFF negative. Patients with MD positive at T1 was significantly associated with poor RFS compared to MD negative (HR = 7.36, 95% CI: 0.93-58.75, Log-rank P=0.028).
Conclusions
Our large-sample study further confirmed that carboplatin plus taxanes NAC in TNBC is an effective regimen choice. Biomarkers based on cfDNA WMS may offer some predictive and prognostic value which needed to be further investigated.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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