Abstract
BackgroundUp-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 89Zr-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.Patients and methods89Zr-trastuzumab PET was performed in patients if disease HER2 status remained unclear after standard work up (bone scan, 18F-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 89Zr-trastuzumab PET.ResultsTwenty 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. 89Zr-trastuzumab PET was positive in 12 patients, negative in 7 and equivocal in 1 patient. In 15/20 patients, 89Zr-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 89Zr-trastuzumab PET result or treatment decision.Conclusion89Zr-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.
Highlights
In metastatic breast cancer, treatment options are largely dependent upon the presence of the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), in addition to tumour load and location
The 89Zr-trastuzumab positron emission tomography (PET) scan was requested by the referring physicians due to following reasons (Supplementary Table S2): (i) To differentiate between metastases of two primary cancers, either two primary breast cancers, or a HER2-positive breast cancer and a second primary cancer from another origin (N = 8), (ii) to assess HER2 status of a single lesion
circulating tumour cells (CTCs) result was not correlated to 89Zr-trastuzumab PET result or subsequent treatment decision. In this small prospective clinical feasibility trial we show for the first time that 89Zr-trastuzumab PET can support diagnostic understanding and clinical decision making when HER2 status of metastatic or locally recurrent breast cancer cannot be determined by standard work up
Summary
Treatment options are largely dependent upon the presence of the oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2), in addition to tumour load and location. The outcome of HER2 positive metastatic disease has fundamentally improved since the development of effective HER2 targeting agents such as trastuzumab, pertuzumab and trastuzumabemtansine [1] In this light, it is of particular interest that HER2 status can change during disease course, necessitating anti-HER2 therapy adjustment. Temporal and spatial heterogeneity may fundamentally affect HER2 status and treatment response Based on this data, clinical guidelines encourage repeat biopsies during the course of the disease. In this feasibility trial we assessed whether 89Zr-trastuzumab PET could support diagnostic understanding and aid clinical decision making, when HER2 status could not be determined by standard work up. Diagnostic understanding and treatment decision questionnaires were completed by the referring physicians before, directly after and ≥ 3 months after 89Zr-trastuzumab PET
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