Abstract 3281: Functional evaluation of response to targeted therapy in HER2 overexpressing inflammatory breast cancer (IBC) patients using positron emission mammography (PEM)
Authors: Yang Wei T. , Rohren Eric , Mawlawi Osama , Krishnamurthy Savitri , Wei Wei , Cristofanilli Massimo , Lucci Anthony , Buchholz Thomas 
Published: February 2011

Abstract
Aim: We report the utility of PEM to evaluate response to single agent neoadjuvant lapatinib (a dual inhibitor of HER1/HER2) in HER2 amplified or overexpressing Inflammatory Breast Cancer (IBC) patients.
Methods: Patients with newly diagnosed HER2 amplified/overexpressing IBC were enrolled in a phase II neoadjuvant trial of lapatinib (Tykerb®) at 1500 mg PO QD for 14 days as a run-in period, followed by sequential chemotherapy (paclitaxel followed by FEC75, in combination with lapatinib). Baseline clinical tumor measurements, mammography, sonography, together with PEM and PET/CT scans, and serial biopsies were performed. PEM and biopsies were repeated after the 14 day run-in with single agent lapatinib, together with clinical tumor measurement. PEM uptake value (PUV) pre- and post lapatinib were compared, and correlated with tumor size, proliferation marker Ki67, and PET/CT standardized uptake value (SUV). Statistical analyses included summary statistics, paired t-test for comparing post- and pre-treatment PUV, and Spearman's correlation test to assess the associations between imaging and clinical endpoints.
Results: A total of 9 patients (median age 57 years, range, 39-67) who were imaged with PEM, and had corresponding imaging and pathology results were included in this analysis. The median tumor size was 9 cm, (range 4-11.2 cm). Baseline PUV of the breast showed significant correlation with baseline tumor size (Spearman's r= 0.75, p = 0.035), and with PET/CT SUV (Spearman's r = 0.90, p=0.018). Median baseline PUV in the breast was 4.2 (range, 1.1-10.6), and was significantly decreased to a median PUV of 1.8 (range, 0.7-7.7, p=0.004) post-lapatinib therapy, without observed decrease in clinical tumor size. The absolute decrease in PUV of the breast was significantly correlated to baseline tumor size (Spearman's r = −0.73, p=0.037), but showed no significant correlation with baseline Ki67.
Conclusion: This is the first clinical study to demonstrate that PUV is strongly correlated with tumor size, and with PET/CT SUV, a commonly utilized functional oncologic imaging modality. Significant early decrease in PUV, as a functional response to targeted therapy, is observed suggesting that this imaging modality can be used to evaluate early response to such therapies. Additional analysis evaluating correlations with changes in proliferation and other downstream markers of EGFR/HER2 inhibition, together with pathologic response will be included in the final results of 30 patients.
Funding by Glaxo Smith Kline and State of Texas Rare and Aggressive Breast Cancer Research Program.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3281.