Treatment of the intact primary in women with metastatic breast cancer

Background

Approximately 12,000 women with primary breast cancer present with stage IV disease annually in the United States. The present treatment paradigm is that systemic therapy is the standard of care and surgical therapy for the primary tumor is provided only to palliate symptoms.

Methods

We have examined the impact of local therapy on survival in patients presenting with stage IV breast cancer at initial diagnosis, reporting to the National Cancer Database (NCDB) between 1990 and 1993. In a subsequent study, we reviewed the medical records of women presenting with stage IV breast cancer to Northwestern Memorial Hospital (NMH) over the 10-year period 1995–2005. Cox regression models and logistic regression was used to estimate adjusted overall survival in both studies, and the time to first progression (TTFP) and chest wall status in the NMH population.

Results

A total of 16,024 patients with stage IV disease were identified in the NCDB over 4 years, of whom 42.8% received only diagnostic or palliative procedures, and 57.2% underwent partial or total mastectomy. A multivariate proportional hazards model identified the number of metastatic sites, the type of metastatic burden, and the extent of resection of the primary tumor as significant independent prognostic covariates. Women treated with surgical resection with free margins, when compared with those not surgically treated, had superior prognosis, with a hazard ratio of 0.61 (95% CI 0.58–0.65). In the NMH study, we identified 114 women; 48 (42%) underwent resection of the primary tumor. Local control of the chest wall was maintained in 36/48 (75%) of the surgical group, versus 31/66 (47%) patients without surgical therapy (P = 0.002). TTFP was prolonged in the surgical group, adjusted HR 0.639 (P = 0.03). The HR for overall survival in the surgical group was 0.724 (P = 0.160). Notably, in women with controlled chest walls we observed an overall survival benefit with a HR of 0.418 (P < 0.0002).

Conclusion

Recent retrospective studies suggest that surgical resection of the primary tumor in women who also have distant disease may be beneficial [1–3]. These are remarkably consistent in the magnitude of the survival advantage, with a hazard ratio of about 0.6 when surgical intervention is used. There is a paucity of data supporting the assumption that surgical resection will maintain a disease-free chest wall. A study of women with in-breast recurrence of breast cancer and synchronous distant metastases found that women undergoing resection were more likely to avoid uncontrolled chest-wall disease and to survive longer [4]. Our study at NMH (the largest reported to date examining this issue) finds that maintenance of a disease-free chest wall is associated with improved survival. This further emphasizes the need for prospective randomized trials to establish the role of local therapy in the setting of metastatic breast cancer.