Incidence and risk factors for central nervous system (CNS) metastases in HER2-positive (HER2+) metastatic breast cancer (MBC) patients (pts)

Abstract

10516 Background: Recently, an increased incidence of CNS metastases in HER2+ MBC has been reported. Aims of the observational study were to evaluate the incidence and risk for CNS metastases in HER2+ MBC pts. Methods: We reviewed the occurrence of CNS metastases in 122 consecutive HER2+ MBC pts treated with chemotherapy (CT) and trastuzumab (T)between April 1999 and June 2005. Patient characteristics included: median age 48 yrs (28–79); G3 in 58.1%;ER- in 53.2%; DFS <24 mos in 48.3% and ≥24 mos in 51.7%. Visceral metastatic disease was dominant site of relapse in 67.2% of the pts. T+CT represented the 1st line of treatment in 54% of pts, 2nd line in 28.6% and ≥3th line in 17.2%. Results: At median follow up of 28 mos (2–167) from the occurrence of metastatic disease, 43 pts (35.2%) developed CNS metastases, confirmed by CT or MRI scanning. In 42 pts were present one or more parenchymal brain metastases and in 1 pt leptomeningeal carcinomatosis. Neurological symptoms were present in 90% of pts. Out of the 43 pts developing CNS metastases, 37.2% were in response in other metastastic sites and CNS represented the only site of progression. Median time of occurrence of CNS metastases (from diagnosis of metastatic disease) was 12 mos (0–78).Using the presence/absence of CNS metastases as dependent variable in logistic regression analysis, we obtained that age (p = 0.020) and visceral metastases (p = 0.024) were significantly associated with increased risk of CNS metastases. Panencephalic RT was given in 31 out of 43 pts; 16 pts (37.2%) received T ± further CT and 18 pts (41.8%) only cytotoxic CT. Median OS was 51.2 mos (1.9+-167.4) in the all population. Median OS was 35 mos (4–105) in pts with CNS metastases; at the present analysis median OS has not been reached in pts without CNS metastases (p = 0.002). Conclusions: CNS metastases is common, late event in the natural history of HER2-positive MBC. Age and visceral metastases were significantly associated with increased risk for CNS metastases. Clinical trials are indicated to evaluate:1) any clinical, pathological and molecular risk factors for CNS metastases; 2) if there is indication to specific treatment in a population at high risk of CNS metastases. No significant financial relationships to disclose.