Predictive Benefit of HER4 Testing in Invasive Breast Carcinoma Patients Receiving Preoperative Trastuzumab-Based Therapy in the Neoadjuvant Setting
Bryce P Portier, Zhen Wang, Eugene Mincae, Erinn Downs-Kelly, Chris Lanigan, Julie Jay, David Tast, Jim Ranger-Moore, Eric Walk, Raymond Tubbs. Cleveland Clinic, Cleveland, OH; Ventana Medical Systems Inc., Tucson, AZ
Background: Common prognostic/predictive markers utilized in breast cancer testing include ER, PR, Ki67, and HER2. Positivity for HER2 by IHC or FISH serves as eligibility for anti-HER2 based Trastuzumab (Genentech, USA) therapy. Response to Trastuzumab in HER2 positive patients is variable, suggesting that additional markers could add predictive value. Recent evidence has implicated a role for HER4 in predicting response to Trastuzumab therapy. In this study, we retrospectively examined the amplification and expression status of both HER4 and HER2 in a cohort of breast carcinomas receiving preoperative Transuzumab in the neoadjuvant setting to elucidate if combination testing added predictive or prognostic value.
Design: All patients (pts) that received Trastuzmab at the Cleveland Clinic from 1/2008 to 12/2010 were reviewed for study inclusion (234 patients); 47 pts met inclusion criteria which included a diagnosis of primary invasive breast cancer, neoadjuvant Trastuzumab therapy, and a pre-treatment biopsy performed at the Cleveland Clinic. These biopsy specimens were analyzed for HER2 via IHC (4B5), FISH (PathVysion), Dual ISH, and Q-RT-PCR; HER4 via IHC (E200) and Q-RT-PCR. Electronic medical records were reviewed for outcome measures including metastasis free survival, overall survival (OS), and complete pathologic response (CpR).
Results: Utilizing IHC and molecular methods, four individual patient populations were segregated: 1) HER4-pos/HER2-pos (12 pts), 2) HER4-neg/HER2-pos (24 pts), 3) HER4-pos/HER2-neg (6 pts), and 4) HER4-neg/HER2-neg (5 pts). Investigation of all four combinations revealed that one population (HER4-pos/HER2-pos), demonstrated statistically significant metastasis free survival compared to the other HER4/HER2 combinations. No significant difference was observed for OS or CpR.
Conclusions: Determination of HER4 amplification/expression in combination with HER2 predicted metastasis free survival in patients treated with Trastuzumab. This finding supports the previously reported protective role of HER4 in Trastuzmab treated breast cancer, and demonstrates the potential prognostic value of dual testing for HER2 and HER4. This data also supports further investigation of HER2 & HER4 testing in a large, well characterized breast cancer cohort to further elucidate the prognostic strength of dual marker testing.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 31, Monday Morning