Different Pathological Complete Response Rates According to PAM50 Subtype in HER2+ Breast Cancer Patients Treated With Neoadjuvant Pertuzumab/Trastuzumab vs. Trastuzumab Plus Standard Chemotherapy: An Analysis of Real-World Data

Tamara Díaz-Redondo; Rocio Lavado-Valenzuela; Begoña Jimenez; Tomas Pascual; Fernando Gálvez; Alejandro Falcón; Maria Del Carmen Alamo; Cristina Morales; Marta Amerigo; Javier Pascual; Alfonso Sanchez-Muñoz; Macarena González-Guerrero; Luis Vicioso; Aurora Laborda; Maria Victoria Ortega; Lidia Perez; Aranzazu Fernandez-Martinez; Nuria Chic; Jose Manuel Jerez; Martina Alvarez; Aleix Prat; Nuria Ribelles; Emilio Alba

doi:10.3389/fonc.2019.01178

Different Pathological Complete Response Rates According to PAM50 Subtype in HER2+ Breast Cancer Patients Treated With Neoadjuvant Pertuzumab/Trastuzumab vs. Trastuzumab Plus Standard Chemotherapy: An Analysis of Real-World Data

Front Oncol. 2019 Nov 5:9:1178. doi: 10.3389/fonc.2019.01178. eCollection 2019.

Authors

Tamara Díaz-Redondo^{1

2}, Rocio Lavado-Valenzuela^{1

3}, Begoña Jimenez^{1

2}, Tomas Pascual⁴, Fernando Gálvez⁵, Alejandro Falcón⁶, Maria Del Carmen Alamo⁷, Cristina Morales⁸, Marta Amerigo⁹, Javier Pascual¹⁰, Alfonso Sanchez-Muñoz^{1

2}, Macarena González-Guerrero¹¹, Luis Vicioso^{1

12}, Aurora Laborda³, Maria Victoria Ortega^{1

12}, Lidia Perez^{1

12}, Aranzazu Fernandez-Martinez¹³, Nuria Chic⁴, Jose Manuel Jerez^{1

14}, Martina Alvarez^{1

3

12}, Aleix Prat⁴, Nuria Ribelles^{1

2}, Emilio Alba^{1

2

3}

Affiliations

¹ Instituto de Investigación Biomédica de Málaga (IBIMA), Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain.
² Unidad de Gestión Clínica Oncología Intercentros, Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain.
³ Laboratorio de Biología Molecular del Cáncer, Centro de Investigaciones Médico-Sanitarias (CIMES), Universidad de Málaga, Málaga, Spain.
⁴ Translational Genomics and Targeted Therapeutics in Solid Tumors Lab (IDIBAPS), Hospital Clinic de Barcelona, Barcelona, Spain.
⁵ Hospital Universitario Ciudad de Jaén, Jaén, Spain.
⁶ Hospital Universitario Virgen del Rocío, Sevilla, Spain.
⁷ Hospital Universitario Virgen Macarena, Sevilla, Spain.
⁸ Hospital Reina Sofía, Córdoba, Spain.
⁹ Hospital Juan Ramón Jiménez, Huelva, Spain.
¹⁰ Hospital Costa del Sol, Marbella, Spain.
¹¹ Hospital Universitario Puerta del Mar, Cádiz, Spain.
¹² Unidad de Gestión Clínica Anatomía Patológica Intercentros, Hospitales Universitarios Regional y Virgen de la Victoria, Málaga, Spain.
¹³ Lineberger Comprehensive Cancer Center, University of North Caroina at Chapel Hill, Chapel Hill, NC, United States.
¹⁴ Departamento de Lenguajes y Ciencias de la Computación, Universidad de Málaga, Málaga, Spain.

Abstract

Background: Double blockade with pertuzumab and trastuzumab combined with chemotherapy is the standard neoadjuvant treatment for HER2-positive early breast cancer. Data derived from clinical trials indicates that the response rates differ among intrinsic subtypes of breast cancer. The aim of this study is to determine if these results are valid in real-world patients. Methods: A total of 259 patients treated in eight Spanish hospitals were included and divided into two cohorts: Cohort A (132 patients) received trastuzumab plus standard neoadjuvant chemotherapy (NAC), and Cohort B received pertuzumab and trastuzumab plus NAC (122 patients). Pathological complete response (pCR) was defined as the complete disappearance of invasive tumor cells. Assignment of the intrinsic subtype was realized using the research-based PAM50 signature. Results: There were more HER2-enriched tumors in Cohort A (70 vs. 56%) and more basal-like tumors in Cohort B (12 vs. 2%), with similar luminal cases in both cohorts (luminal A 12 vs. 14%; luminal B 14 vs. 18%). The overall pCR rate was 39% in Cohort A and 61% in Cohort B. Better pCR rates with pertuzumab plus trastuzumab than with trastuzumab alone were also observed in all intrinsic subtypes (luminal PAM50 41 vs. 11.4% and HER2-enriched subtype 73.5 vs. 50%) but not in basal-like tumors (53.3 vs. 50%). In multivariate analysis the only significant variables related to pCR in both luminal PAM50 and HER2-enriched subtypes were treatment with pertuzumab plus trastuzumab (Cohort B) and histological grade 3. Conclusions: With data obtained from patients treated in clinical practice, it has been possible to verify that the addition of pertuzumab to trastuzumab and neoadjuvant chemotherapy substantially increases the rate of pCR, especially in the HER2-enriched subtype but also in luminal subtypes, with no apparent benefit in basal-like tumors.

Keywords: breast cancer; neoadjuvant; pertuzumab; real-world data; trastuzumab.

Copyright © 2019 Díaz-Redondo, Lavado-Valenzuela, Jimenez, Pascual, Gálvez, Falcón, Alamo, Morales, Amerigo, Pascual, Sanchez-Muñoz, González-Guerrero, Vicioso, Laborda, Ortega, Perez, Fernandez-Martinez, Chic, Jerez, Alvarez, Prat, Ribelles and Alba.