Abstract INTRODUCTION Neoadjuvant chemotherapy (NAC) is increasingly utilized in the treatment of Breast Cancer to downsize the tumour, improve surgical outcome and to achieve a complete pathological response (pCR). Current regimes result in response rates of 40-80% depending on the subtype of the tumour and the presence of pCR, noted in 13-26% patients, is considered an indicator of excellent prognosis. An additional advantage of NAC is the assessment of the in vivo chemo-responsiveness of the tumor.FDG-PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) provides morphologic as well as functional imaging. Preliminary studies suggest it provides a more accurate evaluation of tumour response compared to other techniques. Moreover, studies suggest its utility in identifying non-responders early during NAC so as to enable a switch to an alternate more effective regimen, thereby preventing avoidable toxicity associated with an ineffective drug regimen.In this study, we evaluated metabolic changes on FDG-PET after 2 cycles of NAC to predict pathological response to NAC. PATIENTS AND METHODS A prospective cohort of patients with newly diagnosed, non-metastatic, T1-4, N1-2/3 breast cancer, undergoing NAC from October 2012 to December 2019 at a tertiary referral center, were entered in this study. The tumor size was assessed by the same surgeon at baseline and after every cycle of NAC. FDG-PET/CT was performed before commencement of NAC (PET1) and after the 2nd cycle of NAC (PET2) and the early metabolic response (ΔSUV max i.e. change in maximum standardized uptake value) was determined. All patients underwent surgery on completion of NAC and the pathological response following surgery served as the reference standard for the evaluation of the therapy response on FDG-PET/CT. Patients were classified into Responders [pCR and Minimal Residual Disease (MRD)] and Non-responders [Gross Residual Disease (GRD)] as per the classification of Honkoop et al. Receiver operating characteristic analysis was performed to identify an optimal threshold value of reduction rate (RR) of maximum standardized uptake values (ΔSUVmax) to accurately predict pathological response. RESULTS Out of 135 patients, 4 patients had bilateral cancer, resulting in 139 breast lesions assessed at baseline by FDG PET CT of which 51.07% were Luminal, 21.58% HER2 + and 27.34% TNBC. The mean age was 49 years (range 27-72), 54.81% were premenopausal, 45.19% post-menopausal, 85 (61.15%) were stage II cancers and 54 (38.84%) had stage III cancers. The overall pCR rate was 24.46%, 65 (46.76%) were Responders (pCR+MRD) and 74 (53.23%) Non-responders (GRD). The mean PET1 SUVmax of the tumors in Responder group was 14.5 and of Non-responder group was 9.4. The mean PET2 SUVmax for Responders was 4.28 and Non-responders was 7.52. The RR after the second course of NAC (ΔSUV), was significantly higher for Responders, 62.38% (+24.79) as compared to Non-responders 25.81% (+57.57), (p <0.0001). The optimal ΔSUV threshold to discriminate between Responders and Non-responders was 51% (69.35% sensitivity; 69.12% specificity) with area under the curve being 0.744. The negative predictive value for histopathologic Non-responders was 71.2 (CI 62.2- 78.8). CONCLUSIONS Metabolic change in FDG/PET-CT after 2 cycles of NAC can predict pathological response and, a ΔSUVmax of more than 51%, can differentiate Responders from Non- responders. Early determination of Non-responders could help identify a group which may benefit from an early change to an alternate regimen. Citation Format: Vinay Deshmane, Anuja Raniwala, Abhiyutthan Singh, Sachin Almel, Natasha Singh, Anita Bhaduri, Raj Jatale. The utility of PET-CT after the second cycle of neoadjuvant chemotherapy for monitoring early metabolic change to predict pathologic response [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-43.