Molecular approach to breast cancer treatment.

The tumor biology of the individual patients' disease is increasingly becoming an important factor to consider when choosing a treatment for breast cancer. Equally, there is now more emphasis on understanding the mechanisms of carcinogenesis and how these can be exploited when designing new therapeutic agents. Tumorigenesis in humans is a multistep process involving genetic alterations that drive the progressive transformation of normal cells into malignant types. Dysregulated processes involved in tumorigenesis, such as regulation of cell cycle progression, angiogenesis, and apoptosis provide rational targets for novel therapies. The family of human epidermal growth factor receptors (HER) is well characterized and its role in normal cell growth and tumorigenesis has been extensively researched. Trastuzumab (Herceptin; F. Hoffmann-La Roche, Basel, Switzerland), an anti-HER2 monoclonal antibody (MAb), was one of the first rationally developed and clinically available targeted agents, setting the precedent for providing specific therapy for HER-dysregulated cancer. This and other targeted agents show how research in tumor biology can be used to develop improved cancer therapies. Capecitabine (Xeloda; F. Hoffmann-La Roche) is an example of a rationally designed cytotoxic treatment. It is designed to generate 5-fluorouracil preferentially in tumor cells by exploiting the higher activity of the activating enzyme thymidine phosphorylase in tumors compared with healthy tissues. Tumor-specific activation has the potential to enhance efficacy and minimize toxicity. Proof of this principle is provided by clinical trial results showing that capecitabine is effective and has a favorable safety profile in the treatment of metastatic breast cancer. In summary, we are now at the stage where breast cancer treatment will be determined by tumor biology as well as patient characteristics. Improved molecular characterization and greater understanding of tumorigenesis will enable more individualized treatment.