Although significant advances have been made in the treatment of breast cancer resulting in continued improvement in survival, more than 40,000 women will die of the disease this year.1 Approximately 30% of women diagnosed with early-stage breast cancer will develop a systemic metastatic recurrence, with only a few of these patients achieving long-term survival with standard chemotherapy.2 In addition, 5% to 10% of women are diagnosed with metastatic disease at first presentation of breast cancer. Overall survival (OS) for patients with metastatic disease has changed little over the last 50 years, despite a marked increase in the choice of active agents for treatment. The availability of new targeted biological therapies, particularly trastuzumab for HER-2/neu overexpressing disease, as well as new hormonal and chemotherapeutic agents, has clearly improved outcome for patients with certain biological subtypes of this disease. However, the concept of treating metastatic breast cancer as a chronic disease is still largely theoretical because most patients will survive less than 5 years following diagnosis.
The most significant advances in the treatment of metastatic breast cancer are not limited to the inclusion of new targeted biological therapies. Most recently, the introduction of new cytotoxic agents, new formulations of existing drugs, rationally designed combination therapy, and variation of dose and schedule have resulted in improvements in outcome with generally well-tolerated toxicity profiles. The advantage of these studies is not only seen in improved options for patients with metastatic disease, but also in the ability to test more promising treatment approaches in the adjuvant setting. In addition, there are more options for hormonal therapy, as well as a greater understanding of how and when to use treatment directed toward the estrogen receptor (ER). However, treatments invariably fail, and some tumors are initially resistant to therapy. A better understanding of the biology that drives tumor growth and resistance to therapy has helped to identify new potential targets as well as develop new therapies, but clearly additional study is needed.
The primary goal of treatment for metastatic disease is to control symptoms and to prolong survival in the context of maximizing quality of life. Treatment is palliative, but effective therapy can significantly prolong life. The choice of therapy is based on a variety of factors including biological markers, extent and pattern of disease, prior treatment, patient performance status, and patient preference. Biological markers correlate with the pattern of organ involvement and prognosis; hormone receptor (HR)-positive disease most commonly presents in bone and soft tissues, and visceral involvement is usually limited early in the course of disease. In contrast, visceral involvement dominates in HR-negative and HER-2/neu-positive disease, with risk of pending organ dysfunction. The National Comprehensive Cancer Network provides guidelines for evaluation and treatment of advanced disease that are available online at http://www.nccn.org.
Extent of metastatic disease is an important determinant of therapy and is determined with baseline studies that are also used for future assessment of treatment effect. In addition, ...