Neoadjuvant chemotherapy in breast cancer: a dose-dense schedule in real life and putative role of PIK3CA mutations

// Valentina Cocciolone 1, 2, * , Katia Cannita 2, * , Alessandra Tessitore 1 , Valentina Mastroiaco 1 , Lucia Rinaldi 2 , Stefania Paradisi 2 , Azzurra Irelli 2 , Paola Lanfiuti Baldi 2 , Tina Sidoni 2 , Enrico Ricevuto 1, 3 , Antonella Dal Mas 4 , Giuseppe Calvisi 4 , Gino Coletti 4 , Antonietta Ciccozzi 5 , Laura Pizzorno 6 , Valter Resta 6 , Alberto Bafile 6 , Edoardo Alesse 1 and Corrado Ficorella 1, 2 1 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 2 Medical Oncology Department, S. Salvatore Hospital, University of L’Aquila, L’Aquila, Italy 3 Oncology Network ASL1 Abruzzo, UOSD Oncology Territorial Care, S. Salvatore Hospital, University of L’Aquila, L’Aquila, Italy 4 Pathology Department, S. Salvatore Hospital, L’Aquila, L’Aquila, Italy 5 Radiology Department, S. Salvatore Hospital, L’Aquila, L’Aquila, Italy 6 Breast Unit, S. Salvatore Hospital, L’Aquila, L’Aquila, Italy * These authors have contributed equally to this work Correspondence to: Valentina Cocciolone, email: vale.cocciolone@tiscali.it Keywords: neaodjuvant; dose-dense; PIK3CA; real life Received: July 27, 2017      Accepted: April 06, 2018      Published: June 08, 2018 ABSTRACT Background : Dose-dense chemotherapy is one of the treatments of choice for neoadjuvant therapy in breast cancer (BC). Activating mutations in PIK3CA gene predict worse response to neoadjuvant chemotherapy for HER2-positive patients, while their role is less clearly defined for HER2-negative tumors. Methods : We conducted a phase I/II study of neoadjuvant, sequential, dose-dense anthracycline/taxane chemotherapy, plus trastuzumab in HER2-positive patients and investigated the correlation of pre-treatment PIK3CA mutation status with pathologic complete response (pCR) and long-term outcome in a real-life setting. Results : we established a dose-dense docetaxel recommended dose of 60 mg/m 2 and 65 mg/m 2 , with or without trastuzumab, respectively, according to HER2-status, following dose-dense epirubicin-cyclophosphamide (90/600 mg/m 2 ), every 2 weeks. The overall pCR rate was 21.4%; median disease-free survival (DFS) was 52 months and median overall survival (OS) was not yet reached. PIK3CA mutation status was not significantly associated with the pCR rate: 18% for both mutated and wild-type patients. The pCR rate was: 25% in the mutated and 24% in the wild-type (p 0.560) cohort of the HER2-positive subgroup; 33% both in the mutant and wild-type cohort of the triple-negative subgroup; no pCR neither in the mutant nor in the wild-type cohort of the HR-positive/HER2-negative subgroup. Among the HER2-positive population, a trend toward worse DFS was observed in case of mutation, as opposed to the triple negative population. Conclusions : This study proposes an effective and safe neoadjuvant dose-dense anthracycline/taxane schedule and suggests that PIK3CA mutation analysis can be usefully performed in real-life clinical practice.