Personalizing breast cancer therapy

Breast cancer is the most commonly diagnosed cancer in women and accounts for the highest number of cancer related deaths in females worldwide. The disease is attributed to both genetic susceptibility and environmental factors. Several signalling pathways important for development and therapy of breast cancer have been described, including those mediated by the estrogen receptor and BRCA 1 and 2 genes. Intense research efforts have resulted in the identification of other important pathways implicated in breast cancer development including enzymes that control addition and removal of acetyl groups on histone and non-histone proteins such as p300, SRC1 and SIRT family, as well as genes regulating drug disposition and metabolism such as cytochrome P450 (CYP). In addition, cellular processes that can be deregulated in breast cancer including inflammation, hypoxia and energy metabolism have increased understanding of these signalling pathways and have facilitated the discovery of many therapeutic strategies such as selective estrogen receptor modulators and herceptin, which in combination with conservative therapies have increased survival and quality of life. However, the complexity of the disease, the resistance to therapy and the variations between individual breast cancer patients limit the effectiveness of these drugs emphasizing the need to develop novel more precise, predictable and effective individualized breast cancer therapies. Here we discuss signalling pathways contributing to breast carcinogenesis and recent advances towards refining breast cancer subtypes, identifying novel diagnostic and prognostic biomarkers, and developing personalized patient care.