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Abstract 716: O6-Methylguanine DNA methyl transferase (MGMT) and tamoxifen resistance in patients with breast cancer

Santhi D. Konduri, Sreeram Maddipatla, J. R. Smith, Beth Isley, Maria-Lourdes M Caparas, Susan M. Constantino, Nikita Shah, Said Baidas

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Abstract

Abstract Tamoxifen is an estrogen receptor antagonist in breast tissue. It has been used as a hormonal therapy for early and advanced breast cancer both in premenopausal and postmenopausal patients with estrogen receptor positive breast cancer. Acquired resistance to tamoxifen therapy is a common therapeutic encounter. Different mechanisms for Tamoxifen resistance have been postulated. In the present study we investigated if over expression of MGMT causes tamoxifen resistance in breast cancer patients. Purpose: We sought to determine MGMT expression levels in various breast cancer cell lines as well as in breast cancer patient's samples before and after treatment with tamoxifen. Experimental Design: MGMT expression levels were compared in breast cancer tissue samples obtained from patients before starting treatment with Tamoxifen and after tumor progression due to development of Tamoxifen resistance. MGMT expression level was evaluated using western blot and immunohistochemical assays. Several commercial breast cell lines were evaluated for expression of MGMT. Results: We found that MGMT is over expressed in the majority of breast cancer cell lines compared to normal breast epithelial cells. Compared to pre Tamoxifen treatment, post Tamoxifen treated breast cancer patient samples have significantly higher levels of MGMT expression. Conclusion: Collectively, our results demonstrate that breast cancer cells showed significantly higher levels of MGMT expression and furthermore, Tamoxifen treatment induces further MGMT over expression in breast cancer patients. According to our results over expression of MGMT is a possible cause for Tamoxifen resistance. Inhibition of MGMT might overcome Tamoxifen resistance and restore breast cancer sensitivity to Tamoxifen treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 716. doi:10.1158/1538-7445.AM2011-716

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Abstract Tamoxifen is an estrogen receptor antagonist in breast tissue. It has been used as a hormonal therapy for early and advanced breast cancer both in premenopausal and postmenopausal patients with estrogen receptor positive breast cancer. Acquired resistance to tamoxifen therapy is a common therapeutic encounter. Different mechanisms for Tamoxifen resistance have been postulated. In the present study we investigated if over expression of MGMT causes tamoxifen resistance in breast cancer patients. Purpose: We sought to determine MGMT expression levels in various breast cancer cell lines as well as in breast cancer patient's samples before and after treatment with tamoxifen. Experimental Design: MGMT expression levels were compared in breast cancer tissue samples obtained from patients before starting treatment with Tamoxifen and after tumor progression due to development of Tamoxifen resistance. MGMT expression level was evaluated using western blot and immunohistochemical assays. Several commercial breast cell lines were evaluated for expression of MGMT. Results: We found that MGMT is over expressed in the majority of breast cancer cell lines compared to normal breast epithelial cells. Compared to pre Tamoxifen treatment, post Tamoxifen treated breast cancer patient samples have significantly higher levels of MGMT expression. Conclusion: Collectively, our results demonstrate that breast cancer cells showed significantly higher levels of MGMT expression and furthermore, Tamoxifen treatment induces further MGMT over expression in breast cancer patients. According to our results over expression of MGMT is a possible cause for Tamoxifen resistance. Inhibition of MGMT might overcome Tamoxifen resistance and restore breast cancer sensitivity to Tamoxifen treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 716. doi:10.1158/1538-7445.AM2011-716

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Available abstract

Abstract Tamoxifen is an estrogen receptor antagonist in breast tissue. It has been used as a hormonal therapy for early and advanced breast cancer both in premenopausal and postmenopausal patients with estrogen receptor positive breast cancer. Acquired resistance to tamoxifen therapy is a common therapeutic encounter. Different mechanisms for Tamoxifen resistance have been postulated. In the present study we investigated if over expression of MGMT causes tamoxifen resistance in breast cancer patients. Purpose: We sought to determine MGMT expression levels in various breast cancer cell lines as well as in breast cancer patient's samples before and after treatment with tamoxifen. Experimental Design: MGMT expression levels were compared in breast cancer tissue samples obtained from patients before starting treatment with Tamoxifen and after tumor progression due to development of Tamoxifen resistance. MGMT expression level was evaluated using western blot and immunohistochemical assays. Several commercial breast cell lines were evaluated for expression of MGMT. Results: We found that MGMT is over expressed in the majority of breast cancer cell lines compared to normal breast epithelial cells. Compared to pre Tamoxifen treatment, post Tamoxifen treated breast cancer patient samples have significantly higher levels of MGMT expression. Conclusion: Collectively, our results demonstrate that breast cancer cells showed significantly higher levels of MGMT expression and furthermore, Tamoxifen treatment induces further MGMT over expression in breast cancer patients. According to our results over expression of MGMT is a possible cause for Tamoxifen resistance. Inhibition of MGMT might overcome Tamoxifen resistance and restore breast cancer sensitivity to Tamoxifen treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 716. doi:10.1158/1538-7445.AM2011-716

Key concepts: Tamoxifen, Breast cancer, Medicine, Oncology, Estrogen receptor, Internal medicine, Cancer, Cancer research

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Abstract 716: O6-Methylguanine DNA methyl transferase (MGMT) and tamoxifen resistance in patients with breast cancer — Research Paper | ScholarLens