Abstract 427: c-Met reduces response to radiation in breast cancer

The c-Met receptor promotes cell survival and proliferation by activating signalling pathways. c-Met is abundant in several cancers and in some cases it interferes with treatment response. In vitro, c-Met has been shown to be up-regulated and activated after radiation treatment, which renders the cells resistant to apoptosis and radiation. Therefore, it was hypothesised that high c-Met expression could influence response to radiation in breast cancer. In this study, it was aimed to determine the number of MET gene copies and c-Met protein expression in breast tumours. Tumours of 172 post-menopausal patients with primary breast cancer were analysed for MET using qPCR. Increased MET copy number (three or more copies) was found in 34% of the tumours. Five or more gene copies were found in 4.7% of the patients and indicated a significantly higher risk of developing distant metastasis. For the patients that received radiotherapy as the only postoperative treatment, the number of MET copies was associated with increased risk of distant metastasis. In terms of loco-regional recurrence, it was found that increased MET copy number was associated with worse response to postoperative radiation therapy compared with chemotherapy. c-Met protein analysis by immunohistochemistry in tumours of 208 pre-menopausal patients with primary breast cancer revealed that patients with low expression of c-Met responded better to radiotherapy compared with patients with a high c-Met expression. These results suggest that radiotherapy in combination with a Met inhibitor may be an option for patients with increased c-Met expression, to overcome radio-resistance. Citation Format: Cynthia Veenstra, Gizeh Pérez-Tenorio, Tommy Fornander, Lambert Skoog, Bo Nordenskjöld, Olle Stål. c-Met reduces response to radiation in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 427. doi:10.1158/1538-7445.AM2013-427