Role of breast surgery for stage IV breast cancer Author Michael S Sabel, MD Section Editors Anees B Chagpar, MD,

MSc, MA, MPH, FACS, FRCS(C) Daniel F Hayes, MD Deputy Editor Rosemary B Duda, MD, MPH, FACS Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Nov 2012. | This topic last updated: 18, 2012. INTRODUCTION Patients with metastatic breast cancer are unlikely to be cured of their disease by any means. Complete remissions from systemic chemotherapy are uncommon, and only a fraction of complete responders remain progression-free for a prolonged period. The median survival for patients with stage IV breast cancer is 18 to 24 months, although the range extends from only a few months to many years [13]. (See "Systemic treatment for metastatic breast cancer: General principles" and "Tumor node metastasis (TNM) staging classification for breast cancer".) Approximately 3 to 4 percent of women with newly diagnosed breast cancer present with synchronous stage IV disease. A major question that arises in such patients is how best to manage the primary tumor. The role of surgical excision of the primary tumor in stage IV breast cancer is discussed here. Surgical intervention for metastatic disease in these patients is discussed elsewhere. (See "Metastatic breast cancer: Local treatment".) PALLIATION In the absence of curative treatment for the majority of patients, the goals of therapy typically shift from cure to palliation, focusing on symptom control, improved quality of life (QOL), and prolongation of survival. The typical approach is to perform a core biopsy of the tumor for histologic confirmation of the diagnosis and proceed directly to systemic therapy. Most oncologists consider that once metastases have occurred, there is no survival benefit to aggressive local therapy. However, resection of the primary tumor in stage IV breast disease can provide palliation of bleeding, ulceration or infection [4]. POTENTIAL SURVIVAL BENEFIT There is a subset of women with metastatic breast cancer who have limited systemic tumor burden and biologically indolent disease. Between 5 and 10 percent of patients with stage IV disease survive five or more years, and 2 to 5 percent become long-term survivors [5,6]. These long-term survivors tend to be young, with an excellent performance status, and limited metastatic (sometimes referred to as oligometastatic) disease. For such patients, combined modality approaches, often including surgery, appear to provide a better chance for long-term progression-free survival than chemotherapy alone [7]. The concept of whether resection of the primary tumor impacts survival has been called into question by several retrospective series that describe better outcomes in patients undergoing breast surgery in the presence of known metastatic disease [8-17].

The reason(s) why resection of the primary tumor might improve survival is elusive. Several possibilities exist, including continued dissemination of disease from the primary, increased immune recognition and control of metastatic disease prompted by removal of the primary, or the possibility that the primary tumor may produce factors that promote the growth of distant disease [3] . In addition, some patients with excellent outcomes after surgery in the face of what appears to be metastatic disease may have been incorrectly classified as having stage IV disease. Six of the largest studies of this issue are summarized in the table (table 1) [11-16]. A series of 16,023 patients presenting with stage IV breast cancer derived from the National Cancer Data Base; partial or total mastectomy was performed in 9162, while 6861 underwent a variety of diagnostic or palliative procedures but no breast surgery [11]. Patients who had a margin-negative excision had a significantly better three-year survival compared to those who did not (35 versus 26 percent). Perhaps more importantly, women undergoing complete resection of the primary tumor had a significantly better prognosis when compared to those not surgically treated (hazard ratio 0.61, 95% CI, 0.58-0.65), even when the analysis was adjusted for the type and amount of distant disease and the use of systemic therapy. It is likely however, that these retrospective series and others that demonstrate an association between surgery of the primary site and improved survival simply reflect selection bias (ie, patents perceived to have a longer potential survival are more likely to be offered breast surgery) [3,18]. In a review of 19,464 patients with breast cancer, matched pair analysis showed that the survival benefit associated with primary site surgery in stage IV disease was limited to those patients who received chemotherapy initially rather than surgery followed by chemotherapy [19]. This suggests that patients who have an initially good response to initial chemotherapy are selected to proceed to surgery. It is not clear whether the extent of metastatic disease, the sensitivity to chemotherapy of an individual's tumor, or some combination of these factors identify those women who benefit from surgical resection, or simply permit the selection of individuals who would survive longer regardless of primary site surgery. Although the morbidity and mortality of breast surgery is low, the potential benefits of surgery on local control and survival (if any) must be weighed against the negative aspects of surgery, particularly mastectomy, on a case-by-case basis. INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient

education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient information: Breast cancer guide to diagnosis and treatment (Beyond the Basics)" and "Patient information: Treatment of metastatic breast cancer (Beyond the Basics)").

SUMMARY AND RECOMMENDATIONS

Patients with metastatic breast cancer are unlikely to be cured of their disease by any means. (See 'Introduction' above.) Resection of the primary tumor in stage IV breast disease can provide palliation of bleeding, ulceration or infection. (See 'Palliation' above.) While retrospective studies appear to show a benefit for resection of the primary tumor in women with metastatic breast cancer, this may reflect selection bias and confounding variables. Surgical resection should be considered as a therapeutic option for women with limited metastatic disease, although the risks of surgery must be weighed against the potential benefits. (See 'Potential survival benefit' above.)

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REFERENCES
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