Radiation therapy for brain metastases in breast cancer patients

Most randomized comparison trials (RCTs) investigating treatments for brain metastases (BM) have included BM from any origin; as a result, more than half (52.4-77.0%) of the BM in these trials originated from the lungs (mostly non-small-cell lung cancer, NSCLC), with the breasts being the origin in only 6.8-19.0% of cases. In addition, patients with poor systemic status (KPS < 70) were not included in these trials. Hence, before we can apply RCT-based information to the daily clinical treatment of BM from breast cancers, it will be crucial to differentiate the characteristics of BM originating from NSCLC and BM originating from breast cancer. Although stereotactic radiosurgery (SRS) is widely used in Japan, level-1 evidence suggests that the benefit of using SRS in addition to whole-brain radiation therapy (WBRT) has been proven only for patients with a single BM. Treatment with SRS alone, which is widely used in Japan, seems attractive because it could avoid the risk of long-term adverse effects of WBRT. However, level-1 evidence suggests that the omission of WBRT results in a high frequency of brain tumor recurrence (BTR). In an RCT between SRS-alone and SRS + WBRT conducted in Japan, we found that patients who had a single BM and no extracranial metastases had a low risk of developing BTR after initial brain management (low-risk group) compared with those who had 2 or more BM and extracranial metastases (high-risk group). In order to meet the criteria of "low-risk" BTR, patients also should have good systemic status (KPS ≧ 70). Epidemiologic data suggest that the prognosis is twice as likely to be poor in patients with BM from breast cancer (RPA III = KPS < 70) than in patients with BM from NSCLC (40 vs. 20%); in addition, the probability of brain-only metastases in patients with breast cancer is less than half that in patients with NSCLC (20-25 vs. 60-75%). Considering these findings, we should be aware that most patients with BM from breast cancer are not good candidates for SRS alone, and, therefore, the role of WBRT is still important in the era of modern radiation techniques.