Abstract B48: Germline mutations in BRCA1 and BRCA2 as predictive biomarkers of therapy response

Abstract

Abstract The results of in vitro chemosensitivity studies have shown some consistency with response to chemotherapy in patients, indicating that this approach may be used to identify patients that are resistant to conventional chemotherapy regimens. However, this approach is not routinely used in an adjuvant or neoadjuvant setting as a treatment strategy. Treatment selection for breast and ovarian cancer is currently based on pathological classification of the tumour, without assessment of in vitro chemosensitivity. BRCA1 and BRCA2 germline mutations are considered to be both prognostic cancer biomarkers and predictive biomarkers of breast and ovarian cancer susceptibility; however, their utilization as predictive biomarkers of therapy response has not been investigated. Expression levels of BRCA1 modulate chemosensitivity in breast cancer cell lines, and epigenetic regulation of BRCA1 leading to decreased BRCA1 expression is often observed in sporadic breast cancer. We have hypothesized that cells with mutations in BRCA1 or BRCA2 may be differentially sensitive to DNA damaging agents used in cancer therapy due to decreased levels of BRCA1 or BRCA2 gene expression in these cells. Using lymphocytes isolated from individuals with germline mutations in BRCA1 and BRCA2, we will present results showing the in vitro response to ionizing radiation and chemosensitivity to Paclitaxel and Doxorubicin, two chemotherapeutic agents commonly used in the adjuvant systemic treatment of breast cancer. Citation Information: Cancer Res 2009;69(23 Suppl):B48.