Abstract P4-12-28: HER2-related biomarkers in HER2+ breast cancer patients in Asia Pacific
Authors: Kim S-B , Tsang J , Kim T-Y , Yap YS , Cornelio G , Gong G , Paik S , Lee S , Ng T-Y , Park S , Oh H-S , Yau T , Lee SH , Lim JH , Choi Y-J , Lee EM , Park K-H , Do I-G , Yeoh E-M , Ro J 
Published: August 2014

Abstract
Recent findings suggest that HER2-related molecular markers such as PTEN deletion or downregulation, PIK3CA mutation, truncated HER2 receptor (p95HER2), and tumor HER2 mRNA levels, have the potential to predict anti-HER2 treatment response. We evaluated the distribution of these biomarkers at the time of primary diagnosis and their relationship to responsiveness to lapatinib treatment in the metastatic setting in HER2+ breast cancer patients.
We conducted an observational study of female HER2+ breast cancer patients who were initiated on lapatinib treatment following recurrence or metastases in five Asia Pacific countries. Patients were enrolled between August 2010 and December 2012. Eligible patients had a tumor biopsy specimen available from their primary breast cancer diagnosis or before they started on any anti-HER2 treatment, had not been exposed to more than two lines of anti-HER2 treatment in the metastatic setting or other experimental anti-HER2 treatment, and had no other primary tumor. Biomarkers levels at primary diagnosis were measured; PTEN levels were assessed by immunohistochemistry and PIK3CA mutations were detected by a mass spectroscopy-based approach. The primary endpoint was progression-free survival (PFS) from the initiation of first lapatinib-based regimen given in metastatic setting to disease progression from that regimen or death from any cause. PFS analysis was conducted with a data cut-off date of 31 December 2012.
A total of 162 patients were included in this study and 96% have confirmed HER2+ breast cancer primary tumor. The mean age was 52±10 years and 97% had metastases at study entry, with bone being the most common site of metastasis (48%). About a quarter had PTEN protein loss (24%), 30% had PIK3CA mutation, and 7% had both at primary diagnosis. No significant association was observed between both biomarkers or between each biomarker and estrogen receptor status or HER2 status.
Table 1. Relationship between PTEN and PIK3CA PIK3CA mutation, n (%)PIK3CA wild-type, n (%)p-valuePTEN status 0.674Loss11 (29)27 (71) Normal33 (33)68 (67)
Patients with altered PTEN expression, or PIK3CA mutation showed comparable PFS with lapatinib-based treatment as those with normal PTEN or PIK3CA expression at analysis cut-off date (median PFS 7.5 and 8.5 months respectively vs. 8.9 and 9.0 months respectively; p = 0.502 and p = 0.268 respectively). There remained no significant difference in PFS after having adjusted for significant confounders (HR 1.2 and 1.1 respectively; 95% CI 0.7–1.9 and 0.7–1.8 respectively; p = 0.481 and p = 0.730 respectively). The distribution of p95HER2 expression and tumor HER mRNA levels and their association with PFS will be included at the time of presentation.
Our preliminary findings suggest that PTEN alteration, or PIK3CA mutation may not be predictive of clinical response to lapatinib treatment in HER2+ breast cancer patients. The final PFS results with additional markers will provide more clues regarding their relationship to treatment response.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-28.