Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients

Miolo, Gianmaria, Muraro, Elena, Martorelli, Debora, Lombardi, Davide, Scalone, Simona, Spazzapan, Simon, Massarut, Samuele, Perin, Tiziana, Viel, Elda, Comaro, Elisa, Talamini, Renato, Bidoli, Ettore, Turchet, Elisa, Crivellari, Diana and Dolcetti, Riccardo (2014) Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients. BMC Cancer, 14 1: . doi:10.1186/1471-2407-14-954


Author Miolo, Gianmaria
Muraro, Elena
Martorelli, Debora
Lombardi, Davide
Scalone, Simona
Spazzapan, Simon
Massarut, Samuele
Perin, Tiziana
Viel, Elda
Comaro, Elisa
Talamini, Renato
Bidoli, Ettore
Turchet, Elisa
Crivellari, Diana
Dolcetti, Riccardo
Title Anthracycline-free neoadjuvant therapy induces pathological complete responses by exploiting immune proficiency in HER2+ breast cancer patients
Journal name BMC Cancer   Check publisher's open access policy
ISSN 1471-2407
Publication date 2014-12-15
Sub-type Article (original research)
DOI 10.1186/1471-2407-14-954
Open Access Status DOI
Volume 14
Issue 1
Total pages 1
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background:  Neoadjuvant Chemotherapy (NC) including trastuzumab induces a high rate of pathological Complete Responses (pCR) in patients with locally advanced HER2-overexpressing Breast Cancer (BC), but is penalized by a severe cardiotoxicity when combined with anthracyclines. A phase II study was designed to assess whether an anthracycline-free NC regimen based on the early addition of trastuzumab to paclitaxel may increase the pCR rate without inducing severe cardiotoxicity in patients with locally advanced HER2-overexpressing BC. Immunomonitoring was performed to assess the contribution of patients’ immunological background to the induction of clinical responses.

Methods:  Stage II-III HER2-positive BC patients received 24 weeks paclitaxel and trastuzumab NC, followed by 1 year adjuvant trastuzumab ± hormonal and/or radio-therapy. Assessment of pCR rate was the primary endpoint. A group of HER2-negative BC patients treated with neoadjuvant taxanes and anthracyclines was included. Serum levels of 10 cytokines and the efficiency of trastuzumab-mediated antibody-dependent cell cytotoxicity (ADCC) were monitored in vitro every 3 months.

Results:  From July 2006 to February 2013, we enrolled 109 patients including 46 evaluable HER2-positive cases. A pCR rate of 50% was reached and no severe cardiotoxicity occurred. Serum cytokine profiling revealed only an IL-10 decrease (P = 0.02) in patients achieving a partial response, while HER2-negative patients disclosed marked cytokines changes. Compared to the unfavourable F/F genotype, patients carrying the V allele in the FcγRIIIa-158 polymorphism showed a higher efficacy of trastuzumab-ADCC throughout treatment (P ≤0.05).

Conclusions:  In the absence of anthracyclines, trastuzumab and paclitaxel induced a high rate of pCR, exploiting the synergy between the immunomodulating properties of these drugs and the retained immunological proficiency of patients with HER2-overexpressing BC.
Keyword Breast cancer
HER2
Immune response
Neoadjuvant chemotherapy
Trastuzumab
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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