Central nervous system metastases in patients with high-risk breast carcinoma after multimodality treatment

Background. The current study was performed to determine the incidence of central nervous system (CNS) metastases and to examine associated disease characteristics in a group of patients with locally advanced breast carcinoma (LABC) or inflammatory breast carcinoma (IBC) treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX). Methods. Seven hundred sixty-eight patients treated with multimodality therapy between 1982 and 2000 in any of 6 neoadjuvant trials were eligible for the current study. Five hundred ninety-two patients (77%) had LABC, and 176 (23%) had IBC. CNS disease was defined as the presence of brain metastases or leptomeningeal disease. Time to detection of CNS disease and overall survival were estimated using the Kaplan-Meier product-limit method, and differences were evaluated using log-rank tests. Results. The median patient age was 48 years. Most tumors were classified as T4 lesions (58%) and exhibited lymph node involvement (78%). Fifty-one percent of all tumors had positive hormone receptor status. At a median follow-up duration of 9.5 years, 61 patients (8%) had developed CNS metastases, with the CNS representing the first site of recurrence for 38 of these 61 (63%). Characteristics associated with the development of CNS metastases over time included negative hormone receptor status (P=0.03), Grade 3 disease (P=0.01), and larger tumor size (P=0.02). The median time to detection of CNS metastases was 2.3 years. Ten patients (16%) remained alive after treatment for CNS metastases. The median survival from the time of diagnosis of CNS metastases was 8 months. Conclusions. CNS metastases from breast carcinoma were relatively uncommon and were strongly associated with more aggressive clinical presentation. Survival from the time of diagnosis of such metastases generally was short.