Resecting the Primary When Patients Present with Metastatic Breast Cancer: The Swiss Experience
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC
Dr. Ershler is on the speaker's bureau for Wyeth and does research for Ortho Biotech.
Synopsis: When a woman presents with metastatic breast cancer, the question of surgical excision of the primary tumor often arises. In a series of 300 consecutive patients reported to the Geneva Cancer Registry with primary breast cancer and distant metastases at the time of diagnosis, survival was found to be significantly better for those who had their primary tumor resected. Although this was true for patients with metastatic disease at all sites, the findings were most remarkable for those with skeletal metastases.
Source: Rapiti E, et al. Complete excision of primary breast tumor improves survival of patients with metastatic breast cancer at diagnosis. J Clin Oncol. 2006;24:2743-2749.
The role of primary tumor resection for those who present with disseminated breast cancer has not been established. Rapiti and colleagues performed a population-based study to determine the impact of local surgery on survival in women with breast cancer who, at the time of initial presentation, were known to have distant metastases. They examined all patients recorded at the Geneva Cancer Registry between the years 1977 and 1996. Of the 4,485 women with invasive breast cancer reported during this period, 317 (7%) presented with distant metastases at diagnosis. Of these, 17 were registered at the time of death and were excluded from analysis, leaving a total of 300 patients with distant metastases at the time of initial diagnosis.
Overall, 173 patients (58%) did not receive any kind of resection of their primary tumor, whereas 127 (42%) had either mastectomy (n = 87) or tumorectomy (n = 40). Among women who underwent surgery, 48% (n = 61) had negative surgical margins, 26% (n = 33) had positive margins, and 26% (n = 33) had unknown margins. Women who had complete excision of the primary with negative margins had a 40% reduced risk of breast cancer-related death compared to women who did not have surgery. This mortality reduction was not significantly different among patients with different sites of metastases, but in the stratified analysis the effect was particularly evident for women with bone metastasis only (hazard ratio, 0.2; 95% confidence interval, 0.1-0.4; P = 0.001). In contrast, mortality did not differ significantly between patients who underwent surgery and had positive surgical margins and those who did not undergo surgery. Thus, if a complete (margin-free) excision is possible, and particularly if the metastatic disease is in bone, primary resection for those presenting with metastatic disease should be considered on the basis of these findings.
Commentary
Metastatic breast cancer remains an unmet challenge with systemic therapy the mainstay. For patients who present with distant metastasis, the value of primary resection has been debated for decades without resolution. In some cases it seems warranted to prevent local complications, but some have argued that tumor excision might stimulate growth of metastatic lesions1,2 or that resection does little to alter the natural history of the disease. The current observational study would suggest that survival might actually be enhanced by primary resection; a concept that has not received much attention and one that is worthy of investigation.
The survival advantage was most notable for those with metastatic disease confined to bone, a group that generally has a more favorable prognosis compared to patients with disease at other sites.3,4 Perhaps the value of primary resection for those with incident metastatic disease will be realized to the greatest extent in those who have more indolent disease, such as favorable histological features, hormone receptors and without expression of Her2/neu. In these individuals the natural history is such that the residual primary might be the origin of later-to-come metastatic foci, and resection a preventative measure. For those with the markers of aggressive disease, resection might be predicted to have little value. These, of course, are hypotheses that would optimally be tested in a well constructed, multi-center randomized clinical trial.
This report is an excellent example of the utility of epidemiological studies to debunk unsubstantiated dogma (eg, more aggressive disease is observed after primary resection) and to generate hypotheses worthy of more in-depth probing. However, without evidence derived from clinical trial, the practicing physician considering treatment options for a patient with newly diagnosed disseminated breast cancer must rely on clinical judgment regarding the benefit to be gained from primary tumor resection.
References
- Coffey JC, et al. Excisional surgery for cancer cure: therapy at a cost. Lancet Oncol. 2003;4:760-768.
- Baum M, et al. Does surgery unfavourably perturb the "natural history" of early breast cancer by accelerating the appearance of distant metastases? Eur J Cancer. 2005;41:508-515.
- Briasoulis E, et al. Metastatic breast carcinoma confined to bone: portrait of a clinical entity. Cancer. 2004;101:1524-1528.
- Kang Y, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3:537-549.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content