89Zr-trastuzumab PET supports clinical decision making in breast cancer patients, when HER2 status cannot be determined by standard work up

Abstract

Up-to-date information on human epidermal growth factor receptor 2 (HER2) status in breast cancer (BC) is important, as expression can vary during the course of the disease, necessitating anti-HER2 therapy adjustments. Repeat biopsies, however, are not always possible. In this feasibility trial we assessed whether 89 Zr-trastuzumab PET could support diagnostic understanding and aid clinical decision making, when HER2 status could not be determined by standard work up. Additionally, HER2 status on circulating tumour cells (CTCs) was assessed. 89 Zr-trastuzumab PET was performed in patients if disease HER2 status remained unclear after standard work up (bone scan, 18 F-FDG PET, CT and if feasible a biopsy). PET result and central pathologic revision of available tumour biopsies were reported to the referring physician. CTC HER2 status prior to PET was evaluated afterwards and therefore not reported. Diagnostic understanding and treatment decision questionnaires were completed by the referring physicians before, directly after and ≥ 3 months after 89 Zr-trastuzumab PET. Twenty patients were enrolled: 8 with two primary cancers (HER2-positive and HER2-negative BC or BC and non-BC), 7 with metastases inaccessible for biopsy, 4 with prior HER2-positive and -negative metastases and 1 with primary BC with equivocal HER2 status. 89 Zr-trastuzumab PET was positive in 12 patients, negative in 7 and equivocal in 1 patient. In 15/20 patients, 89 Zr-trastuzumab PET supported treatment decision. The scan altered treatment of 8 patients, increased physicians’ confidence without affecting treatment in 10, and improved physicians’ disease understanding in 18 patients. In 10/20 patients CTCs were detected; 6/10 showed HER2 expression. CTC HER2 status was not correlated to 89 Zr-trastuzumab PET result or treatment decision. 89 Zr-trastuzumab PET supports clinical decision making when HER2 status cannot be determined by standard work up. The impact of CTC HER2 status needs to be further explored.