18 FDG-PET/CT and molecular markers to predict response to neoadjuvant chemotherapy and outcome in HER2-negative advanced luminal breast cancers patients

// Patricia de Cremoux 1, 2 , Lucie Biard 3, 4 , Brigitte Poirot 1 , Philippe Bertheau 5, 6 , Luis Teixeira 2, 7 , Jacqueline Lehmann-Che 1, 2 , Fatiha A. Bouhidel 5 , Pascal Merlet 8 , Marc Espie 2, 7 , Matthieu Resche-Rigon 3, 4 , Christos Sotiriou 9 and David Groheux 2, 8 1 Molecular Oncology Unit, Saint-Louis Hospital, Paris, France 2 University Paris-Diderot, Sorbonne Paris Cite, INSERM/CNRS UMR944/7212, Paris, France 3 Department of Biostatistics, Saint-Louis Hospital, Paris, France 4 University Paris-Diderot, Sorbonne Paris Cite, INSERM UMR 1153 ECSTRA team, Paris, France 5 Department of Pathology, Saint-Louis Hospital, Paris, France 6 University Paris-Diderot, Sorbonne Paris Cite, INSERM UMR-S-1165, Paris, France 7 Breast Diseases Unit, Saint-Louis Hospital, Paris, France 8 Department of Nuclear Medicine, Saint-Louis Hospital, Paris, France 9 Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Universite Libre de Bruxelles, Brussels, Belgium Correspondence to: Patricia de Cremoux, email: patricia.de-cremoux@aphp.fr Keywords: breast cancer; neoadjuvant chemotherapy; TP53 status; 18 FDG-PET/CT; pathological complete response Received: December 20, 2017     Accepted: February 26, 2018     Published: March 27, 2018 ABSTRACT Background: The efficacy of neoadjuvant chemotherapy regimens in advanced luminal breast cancer patients is difficult to predict. Intrinsic properties of breast tumors, including altered gene expression profile and dynamic evaluation of metabolic properties of tumor cells using positron emission tomography/computed tomography (PET/CT) of tumor cells, have been identified to guide patient’s prognosis. The aim of this study is to determine if both analyses may improve the prediction of response to neoadjuvant chemotherapy in ER-positive / HER2-negative breast cancers (BCs) patients. Methods : We used metabolic PET parameters, at diagnosis and after two cycles of chemotherapy and proliferation gene expression profile on biopsy at diagnosis, in particular, the genomic grade index (GGI) analyzed by reverse transcription and quantitative polymerase chain reaction (RT-qPCR). The pathological response was the surrogate endpoint. Results: The change of FDG uptake between baseline PET and interim PET after 2 cycles of neoadjuvant chemotherapy (ΔSUVmax) was highly associated with pCR (p=0.008). We also observed an ability of P53 mutated status (p=0.042), in addition to histological grade (p=0. 0004), and PR expression (p=0.01) to predict pCR in ER-positive BCs, whereas no proliferation marker predicted pCR (P=0.39 for GGI). Finally, only ΔSUVmax was significantly associated with event free survival (p=0.047). Conclusions: Our results confirm the predictive and prognostic value of tumor ΔSUVmax in ER-positive /HER2-negative advanced BCs patients. These findings can be helpful to select high-risk patients within trials investigating novel treatment strategies.