343P - New immunohistochemical markers predictive of response to neoadjuvant chemotherapy plus trastuzumab in HER2-positive locally advanced breast cancer:...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Breast Cancer, Locally Advanced
Translational Research
Presenter Giovanni Faggioni
Authors G. Faggioni1, C. Ghiotto1, E. Orvieto2, S. Valpione3
  • 1Medical Oncology 2, Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT
  • 2Anatomia Patologica, Azienda Ospedaliera di Padova, 35128 - Padova/IT
  • 3Istituto Oncologico Veneto IRCCS, 35128 - Padova/IT

Abstract

We present the results of a prospective pilot study aimed to investigate the value of new immunohistochemichal predictive markers of response to chemotherapy in locally advanced HER-2 breast cancer. pTEN loss, pAKT and HER-3 overexpression cause PI3K activation and induce resistance to trastuzumab in vitro and in vivo, with poorer clinical responses in patients with advanced disease. We studied the espression of EGFR, HER-3, pTEN and pAKT in 31 patients with locally advanced HER-2 positive breast cancer who received neoadjuvant chemotherapy plus trastuzumab. Mean age of patients was 55.7 years (median 55, 95% CI 44,2-63,5 years). Results of immunohistochemistral staining are reassumed in the table.

Mean Median 25% C.I. 75% C.I.
ER% 40,6 40,0 0,0 77,5
PgR% 23,1 10,0 0,0 40,0
Ki-67% 38,2 40,0 25,0 50,0
EGFR Hscore 6,1 0,0 0,0 1,0
HER3 (% positive cells) 50,0 50,0 32,5 70,0
HER3 intensity 1,5 1,0 1,0 2,0
HER3 H score 82,6 70,0 32,5 115,0
PTEN (% positive cells) 48,9 70,0 2,5 70,0
PTEN intensity 1,5 1,0 1,0 2,0
AKT Hscore 56,7 20,0 0,0 70,0
AKT IRS 2,5 2,0 0,0 3,0

Patients were homogeneous for tumor burden at diagnosis and received anthraciclin-taxane and trastuzumab-based neoadjuvant treatment. 14 out of 31patients achieved pathological complete remission. Ki-67 and HER3 H score were significatively higher in patients who achieved complete remission (medians were 45.5% versus 25%, p = 0.022; 100% versus 50%, p = 0.045 respectively. We found a correlation between EGFR H score and HER3 Hscore (p = 0.02), and an inverse correlation between age and EGFR H score (p = 0.05) and between PgR and AKT intensity (p = 0.03). Ki-67 and HER3 H score maintained significatively different medians in the group of patients who experienced pathological complete response versus the group on incomplete responders with multivariate analysis (p < 0.01).

Disclosure

All authors have declared no conflicts of interest.