EGFR, MAPK, and Akt status by immunohistochemistry (IHC) are not correlated with clinical outcome in HER2-positive (HER2+) metastatic breast cancer (MBC) patients (pts) treated with trastuzumab (T) with or without chemotherapy (CT)

Abstract

1090 Background: T alone or in combination with CT has been shown to be an active therapy in HER2-positive MBC pts. However, not all pts will benefit and mechanisms of resistance to T are still poorly understood. The aim of this study was to evaluate the IHC expression of EGFR and two downstream effectors of the EGFR family signaling pathway, MAPK and Akt and their correlation with clinical outcome in HER2-positive MBC pts treated with T ± CT. Methods: 133 consecutive HER2+ MBC pts were treated between 04/99 and 03/06 but tumor tissue was available for this analysis only from 45 pts. HER2 evaluated by CB11 was scored according to Herceptest. Tumors were considered EGFR positive if =1% positive tumor cells and MAPK positive and Akt positive if the percentage of positive tumor cells was =10%. Results: At median follow up of 57 months (range 5–229) from the start of T, 45 pts were evaluable for TTP and OS and 42 for response to T. Median age of pts was 53 years (23–77). Twenty seven objective responses (CR+PR) to T ± CT (64.28%) were observed; median TTP was 24 months (3.3–179.8). In 11 of the 27 responsive pts (40.7%), progression was observed in CNS ± other sites. Median OS from the start of T was 74 months. EGFR positive tumors were 10 (22.2%), MAPK positive tumors were 16 (35.5%) and Akt positive tumors were 23 (51.1%). We analyzed the correlation of HER2, EGFR, MAPK and Akt status with response to T, TTP and OS. HER2 was significantly correlated with response to T (p = 0.013): in HER2 3+ tumors we observed 22 (9 CR and 13 PR) out of 27 objective responses but, no significant correlation was found between HER2 status and TTP and OS. EGFR, MAPK and Akt status of tumor were not significantly associated with response to T, TTP and OS in this series of HER2+ MBC pts. Conclusions: We did not found any significant correlation between EGFR, MAPK, Akt status evaluated by IHC and clinical outcome in HER2+ MBC pts treated with T ± CT. Only HER2 status evaluated by IHC significantly correlated with response to T ± CT. No significant financial relationships to disclose.