Abstract P5-18-03: Clinicopathological features among patients with HER2-positive breast cancer with prolonged response to trastuzumab based therapy

Background: HER2-positivity is a predictor of benefit from trastuzumab (TRZ), but fails to depict the observed interpatient variability in terms of treatment (tx) duration. In this study we described the relationship between clinicopathological features and TRZ tx duration. Methods: A retrospective consecutive series of 343 HER2+ breast cancer (BC) patients (pts) treated with TRZ at the Dana-Farber Cancer Institute from 1999–2008 was identified. 139 pts treated with 1st line TRZ-based tx were selected for analysis. Pts who received any non-TRZ prior tx for metastatic disease were excluded. TRZ tx duration was defined as time from start of 1st line therapy to the 1st day of 2nd line therapy or death. Central nervous system (CNS) progression with TRZ maintenance was not considered change of tx. Pts were divided equally into 3 groups based on the duration of 1st line tx distribution. Short-term responders (STR) were on the 1st line tx for 15m. An additional group of extremely LTR (ELTR) was defined as being in the 90th percentile of tx duration (>37m). Descriptive analysis was performed; fisher exact test, Kruskal-Wallis and logistic regression methods were used to compare groups. Results: Median follow-up time since metastatic diagnosis was 4 years (y) (range 0–11). Median age at diagnosis was 47y (22–83), 25% of stage I-III pts at diagnosis received adjuvant/neoadjuvant TRZ. The median disease free interval (DFI) was 20m (0–172), median number of metastatic sites was 2(1–5), 68% of pts had visceral disease. Median duration of 1st line tx was 10m (2–105). TRZ was given with CT in 86%, hormone tx in 6% and as monotherapy in 9%. 25% of pts developed CNS progression and continued tx. There were only small absolute differences for clinicopathological characteristics among STR, IR and LTR. ELTR had a median 1st line TRZ tx duration of 49m (37–105) and similar clinicopathological features to LTR. A higher proportion of LTR had hormone receptor (HR)-positive disease compared with STR, however no significant association between LTR and STR was found for HR status, DFI and visceral involvement. Conclusions: TRZ tx duration varies widely in the 1st-line advanced setting. No clinicopathological features were associated with TRZ tx duration. Our results suggest that despite CNS progression some pts continue to have long term benefit to TRZ tx. A major research priority is to identify molecular predictors of benefit and resistance to anti-HER2-based therapies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-03.