The value of platinum-based adjuvant chemotherapy in patients with triple-negative breast cancer (TNBC) remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity. OBJECTIVE To compare 6 cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of 3 cycles of cyclophosphamide, epirubicin, and fluorouracil followed by 3 cycles of docetaxel (CEF-T). DESIGN, SETTING, AND PARTICIPANTS This phase 3 randomized clinical trial was conducted at 9 cancer centers and hospitals in China. Between July 1, 2011, and April 30, 2016, women aged 18 to 70 years with operable TNBC after definitive surgery (having pathologically confirmed regional node-positive disease or node-negative disease with tumor diameter >10 mm) were screened and enrolled. Exclusion criteria included having metastatic or locally advanced disease, having non-TNBC, or receiving preoperative anticancer therapy. Data were analyzed from December 1, 2019, to January 31, 2020, from the intent-to-treat population as prespecified in the protocol. INTERVENTIONS Participants were randomized to receive PCb (paclitaxel 80 mg/m 2 and carboplatin [area under the curve = 2] on days 1, 8, and 15 every 28 days for 6 cycles) or CEF-T (cyclophosphamide 500 mg/m 2 , epirubicin 100 mg/m 2 , and fluorouracil 500 mg/m 2 every 3 weeks for 3 cycles followed by docetaxel 100 mg/m 2 every 3 weeks for 3 cycles). MAIN OUTCOMES AND MEASURES The primary end point was disease-free survival (DFS). Secondary end points included overall survival, distant DFS, relapse-free survival, DFS in patients with germline variants in BRCA1/2 or homologous recombination repair (HRR)-related genes, and toxicity. RESULTS A total of 647 patients (mean [SD] age, 51 [44-57] years) with operable TNBC were randomized to receive CEF-T (n = 322) or PCb (n = 325). At a median follow-up of 62 months, DFS time was longer in those assigned to PCb compared with CEF-T (5-year DFS, 86.5% vs 80.3%, hazard ratio [HR] = 0.65; 95% CI, 0.44-0.96; P = .03). Similar outcomes were observed for distant DFS and relapse-free survival. There was no statistically significant difference in overall survival between the groups (HR = 0.71; 95% CI, 0.42-1.22, P = .22). In the exploratory and hypothesis-generating subgroup analyses of PCb vs CEF-T, the HR for DFS was 0.44 (95% CI, 0.15-1.31; P = .14) in patients with the BRCA1/2 variant and 0.39 (95% CI, 0.15-0.99; P = .04) in those with the HRR variant. Safety data were consistent with the known safety profiles of relevant drugs. CONCLUSIONS AND RELEVANCE These findings suggest that a paclitaxel-plus-carboplatin regimen is an effective alternative adjuvant chemotherapy choice for patients with operable TNBC. In the era of molecular classification, subsets of TNBC sensitive to PCb should be further investigated.

PurposeNeoadjuvant chemotherapy (NAC) plays a pivotal role in the treatment of locally advanced breast cancer (LABC); however, breast cancer is a heterogeneous disease, individual responses to chemotherapy are highly variable. Therefore, the purpose of the current research is to identify biomarkers that can predict the chemotherapeutic response.Patients and methodsWe recruited 78 patients with primary breast cancer who underwent taxane- and anthracycline-based NAC; these patients were divided into sensitive and resistant groups according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The microRNA microarray was conducted to explore differentially expressed miRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) further validated the relationship between miR-4530 and chemosensitivity in breast cancer patients.ResultsNo significant differences were observed between the two groups regarding the clinicopathological characteristics. miR-4530 showed the most potential involving breast cancer chemosensitivity. Mechanically, RUNX2 was identified one of the direct targets of miR-4530 and responsible for breast cancer chemosensitivity.ConclusionOur results revealed that elevated serum miR-4530 levels may sensitize breast cancer to taxane- and anthracycline-based NAC by suppressing RUNX2; therefore, this miRNA has the potential to be a new biomarker for predicting breast cancer chemosensitivity.

Triple-negative breast cancer (TNBC) is associated with genome-wide instability caused by mutations in homologous recombination repair mechanism, 1 and the application of DNA-damaging compounds has been explored for TNBC. 2 Recently, we performed the PATTERN trial (NCT01216111) to compare six cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of three cycles of cyclophosphamide/epirubicin/fluorouracil followed by three cycles of docetaxel (CEF-T) in the adjuvant setting of early-stage TNBC, and the result indicated a superior efficacy of the carboplatin-containing regimen and good tolerance to both treatments. 3 In this study, we conducted multi-omic profiling on 132 patients in the PATTERN cohort to investigate potential biomarkers for a more precise choice of adjuvant chemotherapy regimen for TNBC. We found that homologous recombination deficiency (HRD) score might serve as a biomarker of adjuvant carboplatin-containing regimen for TNBC, and upregulation of glycolysis and hypoxia-related pathways might participate in underlying mechanisms of anthracycline/taxane-based regimen resistance.The abovementioned 132 patients in the PATTERN cohort have been enrolled into the Fudan University Shanghai Cancer Center Triple-Negative Breast Cancer (FUSCC-TNBC) program to receive whole-exome sequencing, RNA sequencing, and copy number detection. 4 We investigated the association of multi-omic data with relapse-free survival (RFS) to explore potential biomarkers.