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
Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
Cancers (Basel). 2023 Oct 13;15(20):4980. doi: 10.3390/cancers15204980.
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 (Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation.
HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed.
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 on PET/CT-1 and PET/CT-2 (ΔSUV) in patients with a pPR and pCR of -48% and -90% ( = 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% ( = 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.
NAT response evaluation using 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 Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.
约20%的浸润性导管乳腺癌为人类表皮生长因子受体2（HER2）阳性。这些患者接受包括HER2靶向治疗在内的新辅助全身治疗（NAT）。高达65%的患者实现了病理完全缓解（pCR）。这些患者可能本无需手术。然而，术前准确识别pCR仍具有挑战性。MRI上的放射学完全缓解（rCR）仅在73%的患者中与pCR相符。当前的可行性研究调查了使用锆-89（Zr）放射性标记曲妥珠单抗的HER2靶向PET/CT成像是否可用于更准确的NAT反应评估。
计划接受NAT及后续手术的HER2阳性乳腺癌患者在NAT前（PET/CT-1）和后（PET/CT-2）均接受Zr-曲妥珠单抗PET/CT检查。进行了定性和定量反应评估。
纳入6例患者。所有原发肿瘤在PET/CT-1上均可识别。4例患者原发肿瘤实现pCR，2例为病理部分缓解（pPR）。PET/CT的定性评估准确率为66.7%，而标准护理MRI的准确率为83.3%。定量评估显示，pPR和pCR患者PET/CT-1与PET/CT-2上的SUV差值（ΔSUV）分别为-48%和-90%（P = 0.133）。pPR和pCR患者PET/CT-1与PET/CT-2上的肿瘤与血液比值差值（ΔTBR）分别为-79%和-94%（P = 0.133）。3例患者诊断时存在转移性淋巴结，均在PET/CT-1上被识别。所有3例患者均实现了淋巴结pCR。PET/CT对淋巴结的定性评估准确率为66.7%，而MRI的准确率为50%。
使用Zr-曲妥珠单抗PET/CT进行NAT反应评估是可行的。在本研究中，PET/CT图像的定性评估并不优于标准护理MRI。我们的结果表明，Zr-曲妥珠单抗PET/CT的定量评估在更准确评估HER2阳性乳腺癌NAT后原发肿瘤的反应方面具有潜力。
