Author reply

We reviewed the data presented by Altundag et al.1 with much interest. They demonstrated that younger patient age and estrogen receptor (ER)-positive tumors were predictive of a modestly longer overall survival after the diagnosis of central nervous system (CNS) metastases, whereas our data did not demonstrate this finding.2 One potential explanation is that our study population was derived from approximately 50 institutions across the U.S., and may have had somewhat different characteristics compared with that from a single referral institution. ER level assays and cutoff values also may have been different. Another possibility is that our patients were treated in the 1970s and 1980s and did not receive the newer hormonal, chemotherapy, or targeted therapies that were available from the 1990s onward. One such agent is trastuzumab; patients who develop CNS metastases while receiving trastuzumab have been shown to have prolonged survival.3 This most likely is secondary to the fact that approximately half of the patients who develop CNS metastases die from extracranial disease progression.4 Here, trastuzumab therapy was able to control the progression of extracranial disease. Therefore, patients who otherwise would have died of extracranial disease progression are living longer. A similar conclusion could be extrapolated to newer hormonal therapies and chemotherapies. Conversely, survival after the development of CNS metastases does not appear to have altered significantly over the past decades. Therefore, advances need to be made with either more potent radiosensitizers or by using targeted agents that can potentially cross the blood-brain barrier and are able to treat both intracranial and extracranial disease.

Yee Lu Tham MD*, Richard Elledge MD*, * Breast Care Center, Baylor College of Medicine and Methodist Hospital, Houston, Texas.