Research Papers:

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy

Angela Santonja, Alfonso Sánchez-Muñoz, Ana Lluch, Maria Rosario Chica-Parrado, Joan Albanell, José Ignacio Chacón, Silvia Antolín, José Manuel Jerez, Juan de la Haba, Vanessa de Luque, Cristina Elisabeth Fernández-De Sousa, Luis Vicioso, Yéssica Plata, César Luis Ramírez-Tortosa, Martina Álvarez, Casilda Llácer, Irene Zarcos-Pedrinaci, Eva Carrasco, Rosalía Caballero, Miguel Martín and Emilio Alba _

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Oncotarget. 2018; 9:26406-26416. https://doi.org/10.18632/oncotarget.25413

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Angela Santonja1,2,*, Alfonso Sánchez-Muñoz3,4,*, Ana Lluch4,5,6,7, Maria Rosario Chica-Parrado1,2, Joan Albanell4,5,8,9, José Ignacio Chacón5,10, Silvia Antolín5,11, José Manuel Jerez12, Juan de la Haba4,5,13,14, Vanessa de Luque1,2, Cristina Elisabeth Fernández-De Sousa1,2, Luis Vicioso1,15,16, Yéssica Plata17, César Luis Ramírez-Tortosa18, Martina Álvarez1,2,16, Casilda Llácer3, Irene Zarcos-Pedrinaci19,20, Eva Carrasco5, Rosalía Caballero5, Miguel Martín4,5,21 and Emilio Alba2,3,4,5

1Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain

2Laboratorio de Biología Molecular del Cáncer, Centro de Investigaciones Médico-Sanitarias (CIMES), Universidad de Málaga, Málaga, Spain

3Unidad de Gestión Clínica Intercentro de Oncología, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain

4Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, Madrid, Spain

5Spanish Breast Cancer Research Group (GEICAM), Madrid, Spain

6Department of Oncology and Hematology, Hospital Clínico Universitario, Valencia, Spain

7INCLIVA Biomedical Research Institute, Universidad de Valencia, Valencia, Spain

8Cancer Research Program, IMIM (Hospital del Mar Medical Research Institute), Medical Oncology Service, Hospital del Mar, Barcelona, Spain

9Universitat Pompeu Fabra, Barcelona, Spain

10Medical Oncology Service, Hospital Virgen de la Salud, Toledo, Spain

11Medical Oncology Service, Complejo Hospitalario Universitario de A Coruña, La Coruña, Spain

12Department of Languages and Computer Science, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain

13Medical Oncology Service, Complejo Hospitalario Reina Sofía, Córdoba, Spain

14The Maimonides Institute for Biomedical Research (IMIBIC), Córdoba, Spain

15Department of Pathology, Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain

16Department of Pathology, Faculty of Medicine, Universidad de Málaga, Málaga, Spain

17Department of Oncology, Complejo Hospitalario de Jaén, Jaén, Spain

18Department of Pathology, Complejo Hospitalario de Jaén, Jaén, Spain

19Medical Oncology Service, Hospital Costa del Sol, Marbella, Málaga, Spain

20Health Services Research on Chronic Diseases Network - REDISSEC, Marbella, Málaga, Spain

21Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense de Madrid, Madrid, Spain

*These authors have contributed equally to this work

Correspondence to:

Emilio Alba, email: [email protected]

Keywords: triple negative breast cancer; subtyping; pathologic complete response; neoadjuvant therapy; carboplatin

Received: March 07, 2018    Accepted: April 28, 2018    Published: May 29, 2018


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.

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