Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy
// Angela Santonja 1, 2, * , Alfonso Sánchez-Muñoz 3, 4, * , Ana Lluch 4, 5, 6, 7 , Maria Rosario Chica-Parrado 1, 2 , Joan Albanell 4, 5, 8, 9 , José Ignacio Chacón 5, 10 , Silvia Antolín 5, 11 , José Manuel Jerez 12 , Juan de la Haba 4, 5, 13, 14 , Vanessa de Luque 1, 2 , Cristina Elisabeth Fernández-De Sousa 1, 2 , Luis Vicioso 1, 15, 16 , Yéssica Plata 17 , César Luis Ramírez-Tortosa 18 , Martina Álvarez 1, 2, 16 , Casilda Llácer 3 , Irene Zarcos-Pedrinaci 19, 20 , Eva Carrasco 5 , Rosalía Caballero 5 , Miguel Martín 4, 5, 21 and Emilio Alba 2, 3, 4, 5 1 Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain 2 Laboratorio de Biología Molecular del Cáncer, Centro de Investigaciones Médico-Sanitarias (CIMES), Universidad de Málaga, Málaga, Spain 3 Unidad de Gestión Clínica Intercentro de Oncología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain 4 Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain 5 Spanish Breast Cancer Research Group (GEICAM), Madrid, Spain 6 Department of Oncology and Hematology, Hospital Clínico Universitario, Valencia, Spain 7 INCLIVA Biomedical Research Institute, Universidad de Valencia, Valencia, Spain 8 Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Medical Oncology Service, Hospital del Mar, Barcelona, Spain 9 Universitat Pompeu Fabra, Barcelona, Spain 10 Medical Oncology Service, Hospital Virgen de la Salud, Toledo, Spain 11 Medical Oncology Service, Complejo Hospitalario Universitario de A Coruña, La Coruña, Spain 12 Department of Languages and Computer Science, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain 13 Medical Oncology Service, Complejo Hospitalario Reina Sofía, Córdoba, Spain 14 The Maimonides Institute for Biomedical Research (IMIBIC), Córdoba, Spain 15 Department of Pathology, Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain 16 Department of Pathology, Faculty of Medicine, Universidad de Málaga, Málaga, Spain 17 Department of Oncology, Complejo Hospitalario de Jaén, Jaén, Spain 18 Department of Pathology, Complejo Hospitalario de Jaén, Jaén, Spain 19 Medical Oncology Service, Hospital Costa del Sol, Marbella, Málaga, Spain 20 Health Services Research on Chronic Diseases Network - REDISSEC, Marbella, Málaga, Spain 21 Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain * These authors have contributed equally to this work Correspondence to: Emilio Alba, email: ealbac@uma.es Keywords: triple negative breast cancer; subtyping; pathologic complete response; neoadjuvant therapy; carboplatin Received: March 07, 2018 Accepted: April 28, 2018 Published: May 29, 2018 ABSTRACT Triple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study is to explore the clinical relevance of Lehmann TNBC subtypes by identifying any differences in response to neoadjuvant chemotherapy among them. We determined Lehmann subtypes by gene expression profiling in paraffined pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant anthracyclines and/or taxanes +/- carboplatin. We explored the clinicopathological characteristics of Lehmann subtypes and their association with the pathologic complete response (pCR) to different treatments. The global pCR rate was 37%, and it was unevenly distributed within Lehmann’s subtypes. Basal-like 1 (BL1) tumors exhibited the highest pCR to carboplatin containing regimens (80% vs 23%, p=0.027) and were the most proliferative (Ki-67>50% of 88.2% vs. 63.7%, p=0.02). Luminal-androgen receptor (LAR) patients achieved the lowest pCR to all treatments (14.3% vs 42.7%, p=0.045 when excluding mesenchymal stem-like (MSL) samples) and were the group with the lowest proliferation (Ki-67≤50% of 71% vs 27%, p=0.002). In our cohort, only tumors with LAR phenotype presented non-basal-like intrinsic subtypes (HER2-enriched and luminal A). TNBC patients present tumors with a high genetic diversity ranging from highly proliferative tumors, likely responsive to platinum-based therapies, to a subset of chemoresistant tumors with low proliferation and luminal characteristics.