<sup>89</sup>Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study

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...

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Main Authors: D. G. J. Linders, M. M. Deken, M. A. van Dam, M. N. J. M. Wasser, E. M. C. Voormolen, J. R. Kroep, G. A. M. S. van Dongen, D. Vugts, H. M. Oosterkamp, M. E. Straver, C. J. H. van de Velde, D. Cohen, P. Dibbets-Schneider, F. H. P. van Velden, L. M. Pereira Arias-Bouda, A. L. Vahrmeijer, G. J. Liefers, L. F. de Geus-Oei, D. E. Hilling
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/15/20/4980
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Summary: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</sup>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</sup>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 pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUV<sub>R</sub> on PET/CT-1 and PET/CT-2 (ΔSUV<sub>R</sub>) in patients with a pPR and pCR of −48% and −90% (<i>p</i> = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was −79% and −94% (<i>p</i> = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. Conclusions: NAT response evaluation using <sup>89</sup>Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of <sup>89</sup>Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.
ISSN:2072-6694