Occult central nervous system (CNS) involvement in patients (pts.) with metastatic breast cancer: Prevalence, predictive factors and impact on overall survival

Background: CNS imaging is not routinely performed in asymptomatic pts. with advanced breast cancer, thus the incidence and clinical relevance of occult CNS metastases remains unknown. Despite the lack of data, pts. with CNS involvement are regularly excluded from clinical trials Methods: All pts. screened for participation in one of four clinical trials evaluating novel anti-angiogenic agents in the treatment of metastatic breast cancer were included in this analysis. Each of the trials excluded pts. with CNS involvement and required either a head CT or brain MRI prior to enrollment. Demographic and disease characteristics were abstracted from the medical record. Results: From 11/98 to 5/01, 113 screening imaging studies were performed; 11 pts. were screened twice. Median age at diagnosis was 41.7 years (range 25-76); median interval to first metastasis was 22 mos. (range 0-180). Pts had had metastatic disease for a median of 12.5 mos. prior to screening. Pts. were heavily pretreated with a median of three prior chemotherapeutic regimens (range 0-13); 50% expressed the estrogen receptor; 20% overexpressed HER-2. All pts. had an ECOG PS of 0-1. Seventeen patients (15%) were found to have occult CNS metastases. Identification of occult CNS metastases by CT (7/54) and MRI (10/ 58) was similar. PS (p=0.0079), HER-2 (p=0.026) and age (p=0.05) were predictive of CNS involvement by univariate analysis but only age (p=0.029) remained predictive in multivariate analysis. Over 50% of pts. have died; median survival from time of metastasis was 1.83 years, in pts. with CNS involvement and 1.78 years in patients without CNS involvement. Conclusion: The incidence of occult CNS metastases in pts, with metastatic breast cancer is much higher than previously suspected and may warrant regular screening in selected pts. The impact of occult CNS disease on overall survival appears limited; exclusion of pts. with CNS involvement from clinical trials may not be justified. Additional pts. are being screened and follow-up continues; comparison to pts. with symptomatic CNS metastases is in progress and will be presented at the meeting.