The Management of Asymptomatic Skeletal Breast Cancer: A Paradigm Shift

Abstract

Despite improvements in population screening and health awareness, a significant proportion of women present with advanced breast cancer. The diagnosis of distant metastases mandates systemic rather than local primary intervention. Although incurable, management decisions regarding metastatic breast cancer need not be fatalistic, and early aggressive treatment (both local and systemic) may be appropriate in some patients. In particular, breast cancer confined to bone presents unique characteristics that have been successfully targeted in the palliative setting. Recent evidence suggests that the relationship between the primary focus and the metastasis may be dynamic. Excision of the primary tumor may improve the survival of these patients with the greatest advantage afforded to those with skeletal breast cancer. A potent hypothesis for this observation is that of self-seeding, whereby a high cell production to apoptosis ratio results in inappropriate cell movement. In this model, successful therapy is directed at targets other than cell proliferation (the traditional approach of cytotoxic chemotherapy), including antiangiogenic therapy and, we would argue, surgical resection of the foci with seeding potential. The reason for a survival advantage of bone over visceral metastases remains unclear. Is it a characteristic of the bone or the tumor? Breast cancer s proclivity for bone is a feature distinct from locoregional and visceral spread. The pattern of disease progression, response to palliative therapy and ultimately survival after diagnosis is extremely variable. One explanation for these differences could be the ease with which circulating tumor cells proliferate in secondary tissues. Bone may harbor breast cancer cells at a lower level of metastatic potential than other extramammary sites, and tumor confined to this organ may not have the aggressiveness of breast cancers metastatic to other organs. For this reason, the diagnosis of breast cancer metastases in bone is inadequate for subsequent management decisions. Attention must be given to the presence of concurrent visceral metastases, skeletal tumor load and the expression of target tumor receptors. Skeletal trophism may be due to genetic factors distinct from those which afford metastatic potential. Although bone metastases may be present with disseminated visceral disease, breast cancer confined to the skeleton is associated with longer survival. Identification of the genetic traits that predispose to skeletal breast cancer may identify those patients who would benefit from early and aggressive therapy. Skeletal breast cancer is unique in having a pharmacopoeia that includes targeted therapy for both metastatic cells and the harboring bone. These therapies are supplanting traditional cytotoxic chemotherapy and changing the pattern of disease progression to a degree that may render older survivor data obsolete. Authors Contribution: K. J. Sweeney: Clinical Breast Fellow; P. J. Boland: Attending Orthopedic Surgeon; T. King: Attending Breast Surgeon Received April 2, 2007; accepted May 2, 2007; published online: June 12, 2007. Address correspondence and reprint requests to: Karl J. Sweeney, MD FRCS (gen); E-mail: sweeneyc@mskcc.org