The role of the ErbB2 (HER-2) receptor and p53 mutations in predicting response to taxane chemotherapy is unclear. Preliminary data suggest that ErbB2 positive cells may be resistant while p53 mutant breast cancers may respond well to paclitaxel. We propose to test this hypothesis in a clinical setting involving a cohort of 450 (CALGB) 9342. In this study, patients were randomly assigned to one of three different doses of single-agent paclitaxel. This study is unique in that it allows us to investigate the dose-response relationship of paclitaxel in relation to ErbB2 expression without confounding by other chemotherapy agents in a setting where response rates and time to progression can be used as outcome measures. The overall hypothesis of this study is that increasing doses of paclitaxel will be more effective only in a subgroup of patients identified by ErbB2 status. However, p53 mutated tumors will achieve benefit, even from lower dose of paclitaxel. If true, ErbB2 positively would predict benefit from higher doses of paclitaxel while patients having an ErbB2 negative or 053 mutated tumor could be spared the toxicities of increased dose.
| Harris, Lyndsay N; Broadwater, Gloria; Lin, Nancy U et al. (2006) Molecular subtypes of breast cancer in relation to paclitaxel response and outcomes in women with metastatic disease: results from CALGB 9342. Breast Cancer Res 8:R66 |
