Browsing by Author "Jerez, Y"

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    Pathological Response in a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification
    (American Association for Cancer Research Inc., 2018) Echavarria, I; López-Tarruella, S; Picornell, A; García-Saenz, JÁ; Jerez, Y; Hoadley, K; Gomez, HL; Moreno, F; Monte-Millan, MD; Márquez-Rodas, I; Alvarez, E; Ramos-Medina, R; Gayarre, J; Massarrah, T; Ocaña, I; Cebollero, M; Fuentes, H; Barnadas, A; Ballesteros, AI; Bohn, U; Perou, CM; Martin, M
    Purpose: Triple-negative breast cancer (TNBC) requires the iden- tification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel (TCb).Methods: Patients with TNBC were accrued in a nonrandomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for six cycles. Response was evaluated in terms of pathologic complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans and colleagues. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of seven DNA damage repair genes was conducted.Results: Ninety-four out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR, and 7.4% were classified as ER+. Response to NACT with TCb was significantly associated with Lehmann subtype (P = 0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%), and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2, and 30% were M.Conclusions: TNBCtype-4 is associated with significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT, respectively. Clin Cancer Res; 24(8); 1845-52. ©2018 AACR.
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    TNBC-DX genomic test in early-stage triple-negative breast cancer treated with neoadjuvant taxane-based therapy
    (Elsevier Ltd, 2024) Martín, M; Stecklein, SR; Gluz, O; Villacampa, G; Monte-Millán, M; Nitz, U; Cobo, S; Christgen, M; Brasó-Maristany, F; Álvarez, EL; Echavarría, I; Conte, B; Kuemmel, S; Bueno-Muiño, C; Jerez, Y; Kates, R; Cebollero, M; Kolberg-Liedtke, C; Bueno, O; García-Saenz, JÁ; Moreno, F; Grischke, E-M; Forstbauer, H; Braun, M; Warm, M; Hackmann, J; Uleer, C; Aktas, B; Schumacher, C; Wuerstleins, R; Graeser, M; zu, Eulenburg, C; Kreipe, HH; Gómez, H; Massarrah, T; Herrero, B; Paré, L; Bohn, U; López-Tarruella, S; Vivancos, A; Sanfeliu, E; Parker, JS; Perou, CM; Villagrasa, P; Prat, A; Sharma, P; Harbeck, N
    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. The objective of this study was to evaluate the association between TNBC-DX and efficacy outcomes [pathologic complete response (pCR), distant disease-free survival (DDFS) or event-free survival (EFS), and overall survival (OS)] in the validation cohorts. Methods: Information from 1259 patients with early-stage TNBC (SCAN-B, CALGB-40603, and BrighTNess) was used to establish the TNBC-DX scores. Independent validation of TNBC-DX was carried out in three 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. Results: TNBC-DX test was created incorporating the 10-gene Core Immune Gene module, the 4-gene tumor cell proliferation signature, tumor size, and nodal staging. In the two 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-unit increment 1.34, 95% confidence interval (CI) 1.20-1.52, P < 0.001]. pCR rates for the TNBC-DX pCR-high, pCR-medium, and pCR-low categories were 56.3%, 53.6%, and 22.5% respectively (odds ratio for pCR-high versus pCR-low 3.48, 95% CI 1.72-7.15, P < 0.001). In addition, the TNBC-DX risk score was significantly associated with DDFS [hazard ratio (HR) high-risk versus 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. © 2024 The Author(s)