Quantitative measurements of HER2 and phospho-HER2 expression: correlation with pathologic response to neoadjuvant chemotherapy and trastuzumab

摘要: Preoperative therapy with chemotherapy and the HER2-targeted monoclonal antibody trastuzumab is valuable for patients large or locally advanced HER2-positive (HER2+) breast cancers but traditional methods of measuring HER2 expression do not accurately stratify likelihood response. Quantitative immunofluorescent approaches have potential to provide a mathematically continuous measure HER2. Here we seek determine whether quantitative measurement phospho-HER2 correlates response trastuzumab- containing neoadjuvant therapy. We evaluated core biopsy samples from 27 HER2+ cancer enrolled in preoperative clinical trial using trastuzumab, nab-paclitaxel carboplatin combination (BrUOG BR-211B (NCT00617942)). Tumor biopsies were taken before initiation treatment 9–13 days after received "run-in" doses either single agent nab-paclitaxel. The AQUA method immunofluorescence was used analysis situ protein expression. Patients then 18 weeks treatment, followed by surgery assess pathologic regimen. A score 2111 has been shown be equivalent 3+ immunohistochemical staining previous studies. Of 20 evaluable patients, 10 cases who achieved complete (pathCR) had mean level 10251 compared 4766 without pathCR (p = 0.0021). Measurement showed no difference vs non-pathCR groups. In 9 levels repeated there evidence reduction following that exposure. High are associated achievement setting, while Phospho-HER2 predictive This data suggests accurate may help pre-surgical setting. Further validation larger cohorts required, this pilot shows feasibility approach.