Surgery in metastatic breast cancer: Patients with a favorable profile seem to have the most benefit from surgery
Introduction
With an increasing incidence, breast cancer is still the number one cancer affecting women in the western world. In 2008, 13,097 women were diagnosed with invasive breast cancer in the Netherlands.1 Of all these women, 3–10% had distant metastases at initial presentation. The median survival of these patients is 18–24 months.2 Standard treatment in the Netherlands for metastatic breast cancer consists of palliative systemic therapy with hormonal therapy, chemotherapy and biological therapy. Tumor resection in the breast or axilla is, according to guidelines, only indicated in the palliative setting to prevent skin ulceration, infection or bleeding and to improve quality of life. Recent retrospective studies, however, have shown improved survival in patients who received surgery of the primary tumor, with a hazard ratio ranging from 0.47 to 0.71. Even after adjustment for (among others) age, number of metastatic sites, systemic treatment and receptor status, survival advantages were present.3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 A meta-analysis performed in 2010 showed a pooled hazard ratio for overall mortality of 0.65 (95%CI 0.59–0.72) in favor of the patients undergoing surgery.18
These surgery-favoring results in stage IV disease are not fully understood. One hypothesis is that resection of the primary tumor will result in restoration of the immune system with eradication of cancer stem cells, that are believed to be responsible for the initiation of tumor development, growth, metastatic properties and tumor recurrence. Most retrospective studies, however, do not give detailed information about the timing of surgery and presence of comorbidity. Therefore, the aim of this study was to assess characteristics associated with receiving surgery and to determine the impact of surgery on survival in women with stage IV breast cancer.
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Patients and methods
In this retrospective study we included all women with stage IV breast cancer at time of diagnosis from two Dutch hospitals (Leiden University Medical Centre and HAGA hospital, a large inner-city hospital) in the period 1989–2009. Staging was based on clinical TNM classification.19 The histology grade was grouped in well and moderately differentiated, poorly differentiated and unknown. Metastatic site involvement was categorized as one or more and in the following categories: only bone, only
Results
Overall, 171 patients with stage IV breast cancer at time of diagnoses were included in this study. Table 1 shows the patient characteristics. Of the 171 patients 59 (35%) received surgery of the primary tumor and 112 (65%) did not. Missing data were imputed for ER receptor, PgR receptor, size of the tumor, lymph node status, grade and margins. Of the 59 patients who had surgery of the primary tumor, 21 (35%) were operated with curative intent as the distant metastases were not apparent before
Discussion
The present study shows that younger patients with smaller tumors or a single metastasis who use no medication more often receive surgery for breast cancer with distant metastases. Survival gain was observed in operated patients with a more favorable general health profile; adjusted for potential confounders a survival gain for operated patients was seen in young patients and in patients without comorbidity.
Conclusion
In conclusion, in this retrospective cohort, women with better prognostic characteristics were more often operated. Moreover, in stratified analyses women with the best prognostic characteristics had the best survival. Further research is needed to assess the value of upfront surgery in stage IV disease. Initiatives are now taken in the Netherlands and the United States that hopefully will result in solid conclusions.
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