Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study

• Published in: Cancers 2023-10, Vol.15 (20)
• Main Authors: Linders, D. G. J, Deken, M. M, van Dam, M. A, Wasser, M. N. J. M, Voormolen, E. M. C, Kroep, J. R, van Dongen, G. A. M. S, Vugts, D, Oosterkamp, H. M, Straver, M. E, van de Velde, C. J. H, Cohen, D, Dibbets-Schneider, P, van Velden, F. H. P, Pereira Arias-Bouda, L. M, Vahrmeijer, A. L, Liefers, G. J, de Geus-Oei, L. F, Hilling, D. E
• Format: Article
• Language: English
• Subjects: Adjuvant treatment; Breast cancer; Cancer; Oncology, Experimental; Pertuzumab; PET imaging
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15204980

In breast cancer patients in whom tumor cells overexpress the protein human epidermal growth factor receptor 2 (HER2), HER2-targeted therapy is the mainstay of neoadjuvant therapy (NAT). Two thirds of these patients respond so well to HER2-targeted therapy that during microscopic analysis of the surgically resected tissue, it becomes apparent there are no vital tumor cells left, classified as complete responders. These patients might not have needed surgery. However, with current imaging techniques such as MRI, it remains difficult to preoperatively assess whether there is residual tumor after NAT or not, so all patients still undergo surgery. This study investigated if a HER2-targeted PET/CT scan can reliably assess the response to NAT. In six patients, a HER2-targeted PET/CT scan was acquired before and after NAT. Two out of six patients had residual tumor at microscopic analysis. Visual assessment of the PET/CT scans correctly predicted the response in 66.7% of cases. When the PET/CT signal in both the scan before and after NAT was quantified and (percentual) changes were calculated, there was a difference in the change of signal between patients with and without residual tumor. This difference, although not statistically significant due to the limited patient number in this study, suggests that quantitative assessment of HER2-targeted PET/CT can be used for accurate response evaluation after NAT. Background: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 ([sup.89]Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. Methods: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a [sup.89]Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. Results: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathologica