Identifying Genes Responsible for Tamoxifen Resistance in Breast Cancer

Breast cancer is one of the leading causes of death of women in western countries. It affects one out of eight females in the USA (1) and one out of nine females in The Netherlands (www.kankerregistratie.nl) during their lifetime. Many risk factors for breast cancer have been identified including gender, familial susceptibility, age, and exposure to hormones i.e. use of exogenous hormones, young age at menarge, and high age at menopause and first pregnancy (2). Familial breast cancer accounts for 5-10% of total breast cancer. The remaining 90-95% are called “sporadic”. Occasionally breast cancer also affects males (1% of the breast-cancer incidence in women). In The Netherlands there are approximately 12000 new cases and about 3300 deaths yearly as a result of the disease. Since 1994, the mortality has slightly decreased due to earlier detection, following the introduction of the national breast cancer-screening program, and better treatment strategies (http://www.rivm.nl). Breast cancer patients may be subjected to various treatments including surgery, radiation, chemotherapy, molecular targeted therapy, or endocrine (hormonal) therapy. Often treatment strategies are combined. Surgery forms a part of nearly every patient’s treatment for breast cancer, resulting in partial removal (lumpectomy) or total removal of the breast (mastectomy). Radiation may be used before or after surgery, and may accompany chemotherapy. In molecular targeted therapy, compounds like monoclonal antibodies or small tyrosine kinase inhibitors inhibit a specific target molecule. In contrast to conventional chemotherapy, which acts on all dividing cells generating toxic effects and damage of normal tissues, targeted drugs allow to hit, in a more specific manner, subpopulations of cells directly involved in tumor progression. Endocrine therapy works by interfering with the estrogen pathway that enhances cell-proliferation. It is applied for prevention, adjuvant therapy, and for treatment of metastatic cancers in patients with hormone receptorpositive tumors (3, 4).

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