PT - JOURNAL ARTICLE AU - Gebhart, Geraldine AU - Keyaerts, Marleen AU - Guiot, Thomas AU - Flamen, Patrick AU - Ruiz-Borrego, Manuel AU - Stradella, Agostina AU - Bermejo, Begoña AU - Escriva-de-Romani, Santiago AU - Calvo Martínez, Lourdes AU - Ribelles, Nuria AU - Fernandez-Abad, María AU - Albacar, Cinta AU - Colleoni, Marco AU - Garrigos, Laia AU - Atienza de Frutos, Manuel AU - Dalenc, Florence AU - Prat, Aleix AU - Marmé, Frederik AU - Schmid, Peter AU - Kerrou, Khaldoun AU - Braga, Sofia AU - Gener, Petra AU - Sampayo-Cordero, Miguel AU - Cortés, Javier AU - Pérez-García, José Manuel AU - Llombart-Cussac, Antonio TI - Optimal [<sup>18</sup>F]FDG PET/CT Cutoff for Pathologic Complete Response in HER2-Positive Early Breast Cancer Patients Treated with Neoadjuvant Trastuzumab and Pertuzumab in the PHERGain Trial AID - 10.2967/jnumed.123.266384 DP - 2024 May 01 TA - Journal of Nuclear Medicine PG - 708--713 VI - 65 IP - 5 4099 - http://jnm.snmjournals.org/content/65/5/708.short 4100 - http://jnm.snmjournals.org/content/65/5/708.full SO - J Nucl Med2024 May 01; 65 AB - 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 SUVmax reduction (ΔSUVmax) 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 ΔSUVmax for pCR prediction. Methods: Receiver-operating-characteristic analysis was applied to look for the most appropriate ΔSUVmax cutoff in HER2-positive early breast cancer patients treated exclusively with neoadjuvant HP (with or without endocrine therapy). Results: The ΔSUVmax 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 ΔSUVmax 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 &lt; 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 &lt; 0.001). Conclusion: In the PHERGain trial, an increased SUVmax 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.