Dataset Information

Dose dense versus 3 weekly AC during neoadjuvant chemoimmunotherapy for triple negative breast cancer.

ABSTRACT: Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation.

SUBMITTER: Bonadio RC

PROVIDER: S-EPMC11324725 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Dose dense versus 3 weekly AC during neoadjuvant chemoimmunotherapy for triple negative breast cancer.

Bonadio Renata Colombo RC de Sousa Isadora Martins IM Balint Flávia Cavalcanti FC Comini Ana Carolina Marin ACM Tavares Monique Celeste MC Madasi Fernanda F Bines Jose J Ferreira Rafael Dal Ponte RDP Rosa Daniela Dornelles DD Santos Candice Lima CL de Souza Zenaide Silva ZS Assad-Suzuki Daniele D de Araújo Júlio Antônio Pereira JAP Gagliato Débora de Melo DM Dos Anjos Carlos Henrique CH Zucchetti Bruna M BM Ferrari Anezka A de Brito Mayana Lopes ML Cangussu Renata R Monteiro Maria Marcela Fernandes MMF Hoff Paulo M PM Testa Laura L Barroso-Sousa Romualdo R

NPJ breast cancer 20240814 1

Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treat ...[more]

PMID: 39143082

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Project description:BackgroundNeoadjuvant chemoimmunotherapy (NACI) has emerged as the standard treatment for early-stage triple-negative breast cancer (TNBC). However, reliable biomarkers for identifying patients who are likely to benefit from NACI are lacking. This study aims to develop an intratumoral microbiota-aided radiomics model for predicting pathological complete response (pCR) in patients with TNBC.MethodsIntratumoral microbiota are characterized by 16S rDNA sequencing and quantified through experimental assays. Single-cell RNA sequencing is performed to analyze the tumor microenvironment of tumors with various responses to NACI. Radiomics features are extracted from tumor regions on longitudinal magnetic resonance images (MRIs) scanned before and after NACI in the training set. On the basis of treatment response (pCR or non-pCR) and intratumoral microbiota scoring, we select key radiomics features and construct a fusion model integrating multi-timepoint (pre-NACI and post-NACI) MRI to predict the efficacy of immunotherapy, followed by independent external validation.ResultsA total of 124 patients are enrolled, with 88 in the training set and 36 in the validation set. Tumors from patients who achieves pCR present a significantly greater intratumoral microbiota load than tumors from patients who achieve non-pCR (p < 0.05). Additionally, tumors in non-pCR group exhibit greater infiltration of tumor-associated SPP1+ macrophages, which is negatively correlated with the microbiota load. On the basis of intratumoral microbiota scoring, we select 17 radiomics features and use them to construct the fusion radiomics model. The fusion model achieves the highest AUC of 0.945 in the training set, outperforming pre-NACI (AUC = 0.875) and post-NACI (AUC = 0.917) models. In the validation set, this model maintains a superior AUC of 0.873, surpassing those of pre-NACI (AUC = 0.769) and post-NACI (AUC = 0.802) models. Clinically, the fusion model distinguishes patients who achieve pCR from those who do not with an accuracy of 77.8%. Decision curve analysis demonstrates the superior net clinical benefit of this model across varying risk thresholds.ConclusionsOur intratumoral microbiota-aided radiomics model could serve as a powerful and noninvasive tool for predicting the response of patients with early-stage TNBC to NACI.

Dataset Information

Dose dense versus 3 weekly AC during neoadjuvant chemoimmunotherapy for triple negative breast cancer.

Publications

Dose dense versus 3 weekly AC during neoadjuvant chemoimmunotherapy for triple negative breast cancer.

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