Serum HER2 (sHER2) levels in early-stage HER2 neu (+) breast cancer (HER2+BC): Results from the NCCTG adjuvant Intergroup trial N9831

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529 Background: sHER2 is a circulating oncoprotein cleaved from full-length, membrane-bound HER2. Previous data support that increased sHER concentration is an indicator of poor prognosis and predictor of poor response to chemotherapeutic and hormone treatment in metastatic breast cancer. The role of sHER2 level on the outcome of patients in the adjuvant setting has not been defined, which we evaluated in the context of N9831. Methods: The objectives were to analyze the association between baseline sHER2 and disease-free survival (DFS) in patients (pts) randomized to Arms A (standard chemotherapy) and C (standard chemotherapy with concurrent trastuzumab) of N9831. Baseline serum samples of 1,423 pts from both arms were analyzed for sHER2 using the ADVIA Centaur HER2 assay (Siemens Diagnostics; Tarrytown, NY). Cut off value of 15 ng/mL was used as recommended by the manufacturer/FDA. Patients who cancelled prior to receiving therapy, ineligible pts, and pts whose HER2 status was not corroborated by central review are excluded from analysis. This study uses Cox models stratified by hormone receptor status and nodal status to assess the association between sHER2 levels and DFS. Results: Baseline characteristics between pts with sHER2 <15 ng/mL (N=1,234) and pts with sHER2 ≥15 ng/mL (N=189) demonstrated differences between groups by age, menopausal status (higher sHER2 levels in pts ≥ 50 yrs/post-menopausal), and hormone receptor status (lower sHER2 in hormone receptor + tumors). Hazard ratios between sHER2 groups within Arm A and within Arm C showed that pts with sHER2 ≥15 ng/mL had worse DFS than pts with sHER2 <15 ng/mL (A: HR=1.71, p =0.004; C: HR=1.42, p =0.22). Hazard ratios between arms within each sHER2 group demonstrated similar benefit from trastuzumab in each sHER2 group (<15: HR=0.66, p=0.006; ≥15: HR=0.60, p=0.10). Results remained consistent when including menopausal status and age in the Cox models. Conclusions: 13% of HER2+BC pts of this study had high levels of sHER2. In the standard chemotherapy arm, pts with high sHER2 had significantly worse DFS than pts without. In the concurrent trastuzumab arm, a similar trend was observed but did not reach statistical significance, potentially due to a smaller number of events. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Siemens Healthcare Diagnostics, Inc Genentech™ BioOncology

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