Browsing by Author "Sharma, P"

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Pathological Response and Survival in Triple-Negative Breast Cancer Following Neoadjuvant Carboplatin plus Docetaxel
(American Association for Cancer Research Inc., 2018) Sharma, P; López-Tarruella, S; García-Saenz, JA; Khan, QJ; Gómez, HL; Prat, A; Moreno, F; Jerez-Gilarranz, Y; Barnadas, A; Picornell, AC; Monte-Millán MD; González-Rivera, M; Massarrah, T; Pelaez-Lorenzo, B; Palomero, MI; González Del Val, R; Cortés, J; Fuentes-Rivera H; Morales, DB; Márquez-Rodas, I; Perou, CM; Lehn, C; Wang, YY; Klemp, JR; Mammen, JV; Wagner, JL; Amin, AL; O'Dea, AP; Heldstab, J; Jensen, RA; Kimler, BF; Godwin, AK; Martín, M
Purpose: Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. Patients and methods: One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method. Results: Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14-0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. Conclusions: Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.
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)