P4-17-01: Trastuzumab Does Not Increase the Incidence of Central Nervous System (CNS) Relapses in HER2−Positive Early Breast Cancer: The HERA Trial Experience

Background: Retrospective studies of HER2−positive metastatic breast cancer (BC) showed an incidence of CNS metastases of 21% to 34%. We investigated the incidence and clinical aspects of CNS relapse (CNS-R) in patients (pts) enrolled in the HERA trial, a prospectively randomized adjuvant trial in node + or high-risk node - HER2−positive early BC pts. Methods: 3401 pts were randomized into the 1-year trastuzumab (1yT) or the observation (obs) arms of HERA (Piccart-Gebhart et al, 2005, Gianni et al, 2011). The cumulative incidences of first disease-free survival (DFS) events in the CNS vs other sites were estimated using competing risk analysis. The database of the main study had a clinical cut-off date of 9th June 2008. To obtain additional information regarding CNS-R (including occurrence of CNS-R after first DFS event), a specific CNS-directed questionnaire was sent to investigators of pts who were deceased as of July 2009. Information collected included the date of CNS-R, whether it was symptomatic, the type of CNS-R (brain metastases (BM) or meningeal carcinomatosis (MC)), methods of diagnosis, and treatments at the time of CNS-R. Results: 1yT significantly reduced the risk of other DFS events (p=0.000017, Gray's test), but not of CNS-R (p=0.55) as first event (see table). During the first year of follow up, CNS-R accounted for 15 (14.9%) of the 101 first DFS events in the 1yT arm and 15 (7.7%) of the 194 first DFS events in the obs arm. The analysis of baseline patient and tumor characteristics associated with CNS-R as first event confirmed known risk factors such as young age ( 413 of the 481 questionnaires (85.9%) were returned. 217 of the 413 deceased pts had a CNS-R diagnosed prior to death (52.5%), with more events occurring in the 1yT arm (see table). By contrast, the incidence of CNS-R as first DFS event was balanced across the arms. Based on the survey data, CNS-R was symptomatic in 189 pts (87.1%) with no differences between arms. BM were present in 211 pts (97.2%), absent in 5 (2.3%), and missing information in 1 (0.5%). MC was diagnosed in 25 pts (11.5%), absent in 187 (86.2%), missing information in 5 (2.3%). Frequencies for BM and MC were very similar in both arms. Conclusion: This retrospective analysis of a prospective large study shows more than 50% incidence of clinically diagnosed CNS-R in HER2−positive BC pts who have died. CNS-R was symptomatic in most pts. CNS-R at any time was less frequent in the 1yT arm (88 vs 129). There is no evidence that adjuvant trastuzumab increases the incidence of CNS-R. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-01.