The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)–positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [¹⁸F]FDG PET/CT. [¹⁸F]FDG PET/CT responders were defined as patients with an SUV_max reduction (SUV_max) of at least 40% in all of their target lesions after 2 cycles of trastuzumab and pertuzumab (HP) (with or without endocrine therapy). In total, 227 of 285 patients (80%) included in the HP arm showed a predefined metabolic response and received a total of 8 cycles of HP (with or without endocrine therapy). Pathologic complete response (pCR), defined as ypT0/isN0, was achieved in 37.9% of the patients. Here, we describe the secondary preplanned analysis of the best cutoff of SUV_max for pCR prediction. Methods: Receiver-operating-characteristic analysis was applied to look for the most appropriate SUV_max cutoff in HER2-positive early breast cancer patients treated exclusively with neoadjuvant HP (with or without endocrine therapy). Results: The SUV_max capability of predicting pCR in terms of the area under the receiver-operating-characteristic curve was 72.1% (95% CI, 65.1–79.2%). The optimal SUV_max cutoff was found to be 77.0%, with a 51.2% sensitivity and a 78.7% specificity. With this cutoff, 74 of 285 patients (26%) would be classified as metabolic responders, increasing the pCR rate from 37.9% (cutoff ≥ 40%) to 59.5% (44/74 patients) (P < 0.01). With this optimized cutoff, 44 of 285 patients (15.4%) would avoid chemotherapy in either the neoadjuvant or the adjuvant setting compared with 86 of 285 patients (30.2%) using the original cutoff (P < 0.001). Conclusion: In the PHERGain trial, an increased SUV_max cutoff (≥77%) after 2 cycles of exclusive HP (with or without endocrine therapy) achieves a pCR in the range of the control arm with chemotherapy plus HP (59.5% vs. 57.7%, respectively), further identifying a subgroup of patients with HER2-addicted tumors. However, the original cutoff (≥40%) maximizes the number of patients who could avoid chemotherapy.

^{PHERGain 试验研究了代谢成像在人表皮生长因子受体 2 (HER2) 阳性、侵袭性、可手术乳腺癌（至少有 1 个乳腺病灶可通过 [ 18} F]FDG PET/CT评估）中确定化疗降阶梯候选者的潜力。 [ ¹⁸ F]FDG PET/CT 应答者定义为在 2 个周期的曲妥珠单抗和帕妥珠单抗 (HP)（有或没有内分泌治疗）后，所有目标病灶 SUV_最大降低 (SUV _max ) 至少 40% 的患者。总共，HP 组中的 285 名患者中有 227 名 (80%) 显示出预定的代谢反应，并接受了总共 8 个周期的 HP（有或没有内分泌治疗）。 37.9% 的患者实现了病理完全缓解 (pCR)（定义为 ypT0/isN0）。在这里，我们描述了用于 pCR 预测的 SUV _max最佳截止值的二次预先计划分析。方法：应用受试者操作特征分析来寻找仅接受新辅助 HP 治疗（联合或不联合内分泌治疗）的 HER2 阳性早期乳腺癌患者最合适的 SUV_{最大截止值。}结果：根据受试者工作特征曲线下面积预测 pCR 的SUV_最大能力为 72.1%（95% CI，65.1-79.2%）。最佳 SUV_最大截止值为 77.0%，敏感性为 51.2%，特异性为 78.7%。以此截止值，285 名患者中的 74 名 (26%) 将被归类为代谢反应者，pCR 率从 37.9%（截止值≥ 40%）增加到 59.5%（44/74 名患者）（P < 0.01）。通过这种优化的截止值，285 名患者中有 44 名患者 (15.4%) 将避免在新辅助或辅助治疗中进行化疗，而使用原始截止值的 285 名患者中有 86 名患者 (30.2%) ( P < 0.001)。结论：在 PHERGain 试验中，2 个周期的单纯 HP（有或没有内分泌治疗）后 SUV_最大截止值增加（≥77%），达到了化疗加 HP 对照组范围内的 pCR（59.5% 对比 57.7%） %），进一步确定了 HER2 成瘾性肿瘤患者的亚组。然而，最初的界限（≥40%）最大化了可以避免化疗的患者数量。