Artigo

TNBC-DX genomic test in early-stage triple-negative breast cancer treated with neoadjuvant taxane-based therapy

Autor(es): M. Martín, S.R. Stecklein, O. Gluz, G. Villacampa, M. Monte-Millán, U. Nitz, S. Cobo, M. Christgen, F. Brasó-Maristany, E.L. Álvarez, I. Echavarría, B. Conte, S. Kuemmel, C. Bueno-Muiño, Y. Jerez, R. Kates, M. Cebollero, C. Kolberg-Liedtke, O. Bueno, J.Á. García-Saenz, F. Moreno, E.-M. Grischke, H. Forstbauer, M. Braun, M. Warm, J. Hackmann, C. Uleer, B. Aktas, C. Schumacher, R. Wuerstleins, M. Graeser, C. Eulenburg, H.H. Kreipe, H. Gómez, T. Massarrah, B. Herrero, L. Paré, U. Bohn, S. López-Tarruella, A. Vivancos, E. Sanfeliu, J.S. Parker, C.M. Perou, P. Villagrasa, A. Prat, P. Sharma, N. Harbeck

ABSTRACT

Background: Identification of biomarkers to optimize treatment strategies for early-stage triple-negative breast cancer (TNBC) is crucial. This study presents the development and validation of TNBC-DX, a novel test aimed at predicting both short- and long-term outcomes in early-stage TNBC.

Methods: Information from 1,259 patients with early-stage TNBC (SCAN-B, CALGB-40603, and BrighTNess) were used to establish the TNBC-DX scores. Independent validation of TNBC-DX was carried out in 3 studies: i) WSG-ADAPT-TN, ii) MMJ-CAR-2014-01, and iii) NeoPACT, including 527 patients with stage I-III TNBC undergoing neoadjuvant chemotherapy. In WSG-ADAPT-TN, patients were randomized to receive nab-paclitaxel plus gemcitabine or carboplatin. In MMJ-CAR-2014-01, patients received carboplatin plus docetaxel. In NeoPACT, patients received carboplatin plus docetaxel and pembrolizumab. The objective of this study was to evaluate the association between TNBC-DX and efficacy outcomes (pCR, distant disease-free survival [DDFS] or event-free survival [EFS], and overall survival [OS]) in the validation cohorts.

Results: TNBC-DX test was created incorporating 10-gene core immune gene module, 4-gene tumor cell proliferation signature, tumor size, and nodal staging. In the 2 independent validation cohorts without pembrolizumab, the TNBC-DX pCR score was significantly associated with pCR after adjustment for clinicopathological variables and treatment regimen (odds ratio per 10-units increment=1.34, 95% CI 1.20-1.52, p<0.001). pCR rates for the TNBCDX pCR-high, -medium, and -low categories were 56.3%, 53.6%, and 22.5% respectively (odds ratio for pCR-high vs pCR-low=3.48 [95% CI 1.72-7.15], p<0.001). Additionally, the TNBC-DX risk score was significantly associated with DDFS (hazard ratio [HR] high-risk vs low-risk=0.24, 95% CI 0.15-0.41, p<0.001) and OS (HR=0.19, 95% CI 0.11-0.35, p<0.001). In the validation cohort with pembrolizumab, the TNBC-DX scores were significantly associated with pCR, EFS, and OS.

Conclusions: TNBC-DX predicts pCR to neoadjuvant taxane-carboplatin in stage I-III TNBC and helps to forecast the patient´s long-term survival in the absence of neoadjuvant anthracycline/cyclophosphamide, and independent of pembrolizumab use.

Compartilhar em:

Compartilhar em:

Kit-MKT-Breast-Breaking-NewsAvatar
Breast Breaking News
07/10/2024

Comentários

Deixe um comentário

Carrinho de compras