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Title: Pathological Response in a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification.

Authors: Echavarria, Isabel; López-Tarruella, Sara; Picornell, Antoni; García-Saenz, Jose Ángel; Jerez, Yolanda; Hoadley, Katherine; Gómez, Henry L; Moreno, Fernando; Monte-Millan, María Del; Márquez-Rodas, Iván; Alvarez, Enrique; Ramos-Medina, Rocío; Gayarre, Javier; Massarrah, Tatiana; Ocaña, Inmaculada; Cebollero, María; Fuentes, Hugo; Barnadas, Agusti; Ballesteros, Ana Isabel; Bohn, Uriel; Perou, Charles M; Martin, Miguel

Published In Clin Cancer Res, (2018 04 15)

Abstract: 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.

PubMed ID: 29378733 Exiting the NIEHS site

MeSH Terms: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols/adverse effects; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*; Biomarkers, Tumor; Carboplatin/administration & dosage; Docetaxel/administration & dosage; Female; Gene Expression Profiling; Genes, BRCA1; Genes, BRCA2; Heterozygote; Humans; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Treatment Outcome; Triple Negative Breast Neoplasms/drug therapy*; Triple Negative Breast Neoplasms/mortality; Triple Negative Breast Neoplasms/pathology*; Tumor Burden

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