HER2 predicts benefit from adjuvant paclitaxel after AC in node-positive breast cancer: CALGB 9344

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510 Background: CALGB 9344 showed 4 cycles of paclitaxel (T) after 4 cycles of doxorubicin/cyclophosphamide (AC) improved disease-free (DFS) and overall survival (OS) compared to 4 cycles of AC. Higher dose of A had no benefit (Henderson JCO ’03). Prior studies suggest HER2 is associated with benefit from standard vs low dose of C&A (Dressler JCO ’05). We hypothesized that HER2 might predict benefit from higher dose of A or from T, and that HER2 might refine the observed negative interaction of T with estrogen receptor (ER). Methods: 3121 node + women in CALGB 9344 received 4 q3wk cycles of AC (A: 60, 75, or 90 mg/m2) and then 4 cycles of T (175 mg/m2 q3wk) or no T. Blocks were collected from ∼2800 subjects. 2 sets of 750 patients each were randomly selected from these cases: Set 1 to develop hypotheses; Set 2 for validation. Tissue specimens were available from 643 (set1) and 679 (set2) cases (20% & 22% total enrolled in 9344 respectively). HER2 was evaluated by FISH and by IHC (by antibody cb11 and by Herceptest). Statistical analyses used Cox proportional hazards models, including interaction terms, and Kaplan-Meier estimates for comparing 5-yr DFS by treatment group. Results: In Set 1, all 3 assays suggested that T improved DFS for HER2+ but not for HER2-. For this single set the interaction was not statistically significant. There appeared to be an interaction of HER2, T and ER. IHC using cb11 was applied to Set 2, revealing nearly identical results. In the two sets combined (n=1322), the interaction between HER2 and T was statistically significant (p=0.013). The 3-way interaction of HER2, ER and T was hypothesis-generating and not tested statistically. Differences in 5-yr DFS rates (95% CI) for T vs. no T by HER2 and ER (both sets combined) There was no interaction between HER2 and dose of A. Conclusions: These results suggest that the benefit of adding T to AC is greater for HER2+ tumors, even if ER+, while T was of no apparent benefit in the ER+, HER2- group. Further validation is needed from remaining cases in 9344 and from other trials involving T. [Table: see text] [Table: see text]