Stage IV breast cancer in the era of targeted therapy: does surgery of the primary tumor matter?

The prognosis of patients presenting with stage IV breast cancer has improved over the last decade.1 Recent data suggest that patients are being diagnosed with a lower burden of disease because of improved diagnostic modalities.1 Along with these trends, systemic treatment options have proliferated rapidly and now include several molecularly targeted therapies. As a result, the survival of patients with stage IV breast cancer has improved to a median of 29 months.1 For many patients, the treatment paradigm for stage IV disease is changing and can be viewed as chronic, maintenance therapy. Traditionally, local treatment of stage IV breast cancer, either through surgery or radiotherapy, has been reserved for palliation of advanced local disease.2 However, recent reviews of population and institutional databases suggest that a significant percentage of women (approximately 40-60%) are receiving surgical treatment of their primary tumor as a component of therapy for stage IV disease,3-6 a rate that is considerably higher than what would be expected for palliative purposes alone. Although the clinical rationale for the inclusion of surgery in the treatment of many of these patients with stage IV disease is unclear, these retrospective studies have suggested that surgical resection of the primary tumor is associated with a survival benefit.3-5,7-11 However, in the absence of prospective data, the subset of patients presenting with stage IV disease who are most likely to benefit from surgical resection of the primary tumor is unknown. Although the population database studies addressing the role of surgery in the management of patients with stage IV breast cancer incorporate large cohorts of patients and provide the most generalizable conclusions, they are inherently limited by the clinical variables recorded.12 This is especially significant when it applies to hormone receptor or HER-2/neu status. In addition, clinical details such as indications for the procedure, the specific procedure performed, surgical margin status, and local radiotherapy are unable to be considered. In contrast, single-institution studies may be limited by institutional biases and smaller numbers of evaluable patients. Therefore, any conclusions reached from these series should be considered exploratory. However, the strengths of these single-institution datasets are the degree of clinical detail available. Institution-based studies have the potential to contribute significantly to the literature regarding surgical resection in patients with stage IV breast cancer by identifying those subsets of patients with the greatest potential to benefit from surgical resection—information critical to the design of the prospective clinical trial needed to definitively address this question. In addition, single-institution studies are needed to clarify the magnitude of the problem of uncontrolled local disease in this patient population in the modern era of systemic therapy. Therefore, we sought, in a single-institution study, to explore the role of local control of the breast primary tumor in patients presenting with stage IV disease in the era of molecularly targeted therapy. The objective of the current study was to identify subsets of patients who may benefit from primary tumor treatment and assess the frequency of local disease progression.