Safety, activity, and molecular heterogeneity following neoadjuvant non-pegylated liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab in HER2-positive breast cancer (Opti-HER HEART): an open-label, single-group, multicenter, phase 2 trial

Joaquín Gavilá, Mafalda Oliveira, Tomás Pascual, Jose Perez-Garcia, Xavier Gonzàlez, Jordi Canes, Laia Paré, Isabel Calvo, Eva Ciruelos, Montserrat Muñoz, Juan A Virizuela, Isabel Ruiz, Raquel Andrés, Antonia Perelló, Jerónimo Martínez, Serafín Morales, Mercedes Marín-Aguilera, Débora Martínez, Juan C Quero, Antonio Llombart-Cussac, Aleix Prat, Joaquín Gavilá, Mafalda Oliveira, Tomás Pascual, Jose Perez-Garcia, Xavier Gonzàlez, Jordi Canes, Laia Paré, Isabel Calvo, Eva Ciruelos, Montserrat Muñoz, Juan A Virizuela, Isabel Ruiz, Raquel Andrés, Antonia Perelló, Jerónimo Martínez, Serafín Morales, Mercedes Marín-Aguilera, Débora Martínez, Juan C Quero, Antonio Llombart-Cussac, Aleix Prat

Abstract

Keywords: Breast cancer; HER2; HER2-enriched; PAM50; cardiac safety; intrinsic subtypes; neoadjuvant.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Hospital Vall d’Hebron (Barcelona) AC/R(AG)143/2012(3455). All patients provided written informed consent.

Consent for publication

Not applicable.

Competing interests

Advisory role of AP for Nanostring Technologies. Advisory Role of JG for Roche. The other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
CONSORT diagram
Fig. 2
Fig. 2
Left ventricular ejection fraction (LVEF) changes during neoadjuvant treatment and adjuvant period: from global population in red and from each of six patients who had > 10% drop in LVEF during the study period
Fig. 3
Fig. 3
Molecular heterogeneity of HER2-positive breast cancer. Intrinsic subtype distribution in baseline tumors (a), according to hormonal receptor status (b, c), and in surgical tumors (d). e Pathological complete response (pCR) rates of the intrinsic subtypes identified at baseline
Fig. 4
Fig. 4
Six differentially expressed genes between baseline and surgical specimens. a ESR1, b PGR, c ERBB2, d CD8A, e MKI67, f CCNB1
Fig. 5
Fig. 5
Rates of pathological complete response (pCR) according to the type of chemotherapy and anti-HER2 therapy using data from 15 neoadjuvant clinical trials in HER2-positive breast cancer. Bars denote 95% CIs. T taxane, L lapatinib, H herceptin (trastuzumab), A/T anthracycline/taxane based

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