S5-1: Neoadjuvant Pertuzumab (P) and Trastuzumab (H): Biomarker Analyses of a 4-Arm Randomized Phase II Study (NeoSphere) in Patients (pts) with HER2−Positive Breast Cancer (BC).

摘要: Background: NeoSphere showed that P with H and docetaxel (T) had a significantly higher pCR rate (45.8%) compared TH (29%) or other combinations (HP, TP) (Gianni, SABCS 2010). HER2+/ER+ HER2+/ER− BC have different patterns of gene expression, treatment response seems to be driven by biologic pathways (Bianchini, ASCO 2011). This effect was also seen in NeoSphere. A broad panel biomarkers (BMs) assessed tumor specimens sera characterize the molecular profile ITT population explore BMs treatments subsets pts. Methods: Core biopsies from 387/417 pts collected at baseline were available for BM analyses. HER2, all its truncated forms, HER3, IGF1R, PTEN, pAKT IHC modified H-score derived per each marker. HER1, amphiregulin (AREG) betacellulin mRNA expression tissue qRT-PCR. C-myc FISH. Mutational analyses 8 hot spots within PIK3CA on DNA done via TaqMan-PCR. ELISA used detect HER2 extracellular domain (ECD), AREG, EGF, TGFα serum. Treatment interaction test performed association between pCR. In analysis, median values as cutoffs, except mutation, c-myc amplification, where cutoffs applied following rationale. Results: overall population, high membrane protein measured associated THP arm (p=0.001), large benefit combination (OR=3.74, CI 80%, 2.21−6.34; p=0.0009). The cutoff has no immediate clinical applicability. decreased likelihood detected PI3K mutations 4 arms preliminary analysis limited about 70% cases. final will presented. distribution ER+ vs ER− subgroups found 10 16 (FDR Summary: level increased TH. mutational status appears relevant role defining treatments. effects according ER are reflected tumors, IGF1R score being correlated tumors. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S5-1.