Pharmacogenetics in breast cancer: focus on hormone therapy, taxanes, trastuzumab and bevacizumab

Abstract

Breast cancer is the most common female cancer, with more than one million new patients diagnosed annually worldwide. The great heterogeneity, in terms of prognosis and outcome, within patients with the same clinical and pathological characteristics may limit the potential for personalized therapy. Most of the cytotoxic agents and new targeted agents have a narrow therapeutic index and the administration of an equal dose may result in a wide range of toxicities as well as to different antitumor efficacy. Inter-subject variability in drug toxicity and response is common during treatment, so that individualization of treatments is an important issue. Pharmacogenetics is the study of how inter-individual variations in the DNA sequence of specific genes may affect drug response and toxicity. This article highlights the clinical use of determination of polymorphisms of important human drug-metabolizing cytochrome P450s, ABCB1, IgG fragment C receptors and vascular endothelial growth factor, which are responsible of the large inter-individual variability in drug metabolism and clearance of the agents commonly used in breast cancer treatment, such as tamoxifen, aromatase inhibitors, taxanes, trastuzumab and bevacizumab.

Keywords::

• breast cancer
• pharmacogenetics
• polymorphisms

Acknowledgements

This paper is published as part of a supplement forming the Proceedings of the 5th Annual Conference of the Organisation for Oncology and Translational Research (OOTR). Publication of this supplement is supported by an educational grant from GlaxoSmithKline Ltd. The 5th Annual Conference of OOTR was supported by the following sponsors: GlaxoSmithKline; Pfizer; Novartis; Sanofi-aventis; Roche; AstraZeneca; Genomic Health; Wyeth; Orient Europharma; Medicom; Tin Hang Technology; MacKay Medical Group; Macau Tourism Board.