Management of Hormonal Resistant Breast Cancer

Abstract

Breast cancer is one of the most frequently diagnosed cancers in women worldwide, it accounts for 26 % of all malignancies in women and it’s the most common cause of cancer death in women (Jemal et al., 2011). Breast cancer is a clinically heterogeneous disease. Global gene expression analyses using high throughput technologies have helped to explain much of the heterogeneity of breast cancer and have provided important new molecular classifications. In the last decade, genomic studies have identified five major breast cancer intrinsic subtypes (Luminal A, Luminal B, HER2-enriched, Basal-like and a Normal Breast-like group). These groups of tumors are associated with critical clinical differences and may further provide important knowledge on the biology of breast cancer initiation and progression (Weigelt et al., 2010). The treatment of breast cancer includes the treatment of local disease with surgery, radiation therapy, or both, and the treatment of systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy, or combinations of these. The need for and selection of various local or systemic therapies are based on several prognostic and predictive factors (NCCN Guidelines, 2013). According to the 2011 and 2013 St Gallen guidelines, the decision on systemic adjuvant therapies should be based on the surrogate intrinsic phenotype determined by ER/PR, HER2 and Ki67 assessment (Goldhirsch et al., 2013). All luminal cancers should be treated with Endocrine Therapy (ET). Most luminal A tumors, except those with highest risk of relapse (e.g; extensive nodal involvement), require no chemotherapy, whereas luminal B HER2-negative cancers constitute a population of the highest uncertainty regarding chemotherapy indications. Indications for chemotherapy within this subtype depend on the individual risk of relapse, taking into account the tumor extent and features suggestive of its aggressiveness (grade, proliferation, vascular invasion), presumed responsiveness to ET and patient preferences (Wishart et al., 2011). The ER signaling pathway is an example of a complex biological pathway that controls a variety of functions, such as cell proliferation, apoptosis, invasion, and angiogenesis, and is exploited by breast cancer cells to serve as a major survival pathway driven by the female hormone estrogen. The classic function of ER is its nuclear function, also referred to as genomic activity, to alter the expression of genes important for normal cellular function and tumor growth and survival. ER modulates the expression of hundreds of genes, some by