243 - Impact of PIK3CA mutations and p95HER2 expression on the outcome of HER2-positive metastatic breast cancer patients treated with a trastuzumab-based...

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Biomarkers
Breast Cancer, Metastatic
Presenter Irene Stasi
Authors I. Stasi1, A. Fontana2, G. Allegrini3, C. Mazzanti4, S. Lucchesi5, E. Bona6, I. Ferrarini7, B. Salvadori7, A. Falcone8, K. Zavaglia4
  • 1Medical Oncology, Azienda Ospedaliero Universitaria S.Chiara, 56100 - Pisa/IT
  • 2U.o. Oncologia Medica 2 Universitaria, Polo Oncologico, Ospedale S. Chiara, AOUP, 56100 - Pisa/IT
  • 3Medical Oncology Unit, Pontedera Hospital, 56025 - Pontedera/IT
  • 4University Of Pisa And Pisa University Hospital, Section of Molecular Pathology, Division of Surgical, Molecular, and Ultrastructural Pathology, 56010 - pisa/IT
  • 5Oncologia Medica, OSPEDALE "F. LOTTI", PONTEDERA (PI)/IT
  • 6U.o. Oncologia Medica, Polo Oncologico, Ospedale S. Chiara, AOUP, 56100 - Pisa/IT
  • 7Oncologia Medica Ii, Polo Oncologico, Ospedale S. Chiara, AOUP, 56100 - Pisa/IT
  • 8Oncologia, Trapianti E Nuove Tecnologie In Medicina, Polo Oncologico - Azienda Ospedaliero-Universitaria Pisana - Istituto Toscano Tumori, 56126 - Pisa/IT

Abstract

Background

Currently, no biomarkers of Trastuzumab (T) clinical resistance have been validated. The aim of this pilot study was to evaluate the impact of PIK3CA mutations and p95HER2 (pHER2 truncated form) expression on the efficacy of a T based-therapy in a HER2-positive metastatic breast cancer (MBC) patients (pts).

Methods

107 HER2-positive MBC pts, treated in the last 10 years, were evaluated. Median age was 54 years (25-79); ECOG performance status was 0 in 56% of pts; all pts received several lines of treatment including T; biomarkers molecular analysis was performed in 70 tumor specimens. The IHC expression of p95HER2 was evaluated by a monoclonal antibody that specifically recognizes only the HER2 external domain; the HER2 integrity was defined by the presence of a homogeneous membrane staining (moderate or intense) in at least 30% of the cells, otherwise the HER2 was defined as p95HER2 positive. PIK3CA mutations in exons 9 and 20 were detected by automated sequencing. The molecular data were correlated to Time to progression (TTP) of the first line treatment including T and the Overall Survival (OS) by using the Kaplan-Meir method and the log-rank-test.

Results

p95HER2 positive pts and PIK3CA mutations in exon 9 or 20 were detected in 42% and 22% of tumor specimens, respectively. p95HER2 positive tumors showed a shorter TTP and OS that did not reach statistical significance; PIK3CA mutations correlated with a worse TTP (median 7,6 vs 11,3 months) and OS (median 20,1 vs 41,0 months, p= 0,046).

Conclusions

These preliminary results suggest a possible role of PIK3CA mutational status in predicting the outcome of MBC pts treated with T.

Disclosure

All authors have declared no conflicts of interest.