18FDG-PET/CT and molecular markers to predict response to neoadjuvant chemotherapy and outcome in HER2-negative advanced luminal breast cancers patients
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Patricia de Cremoux1,2, Lucie Biard3,4, Brigitte Poirot1, Philippe Bertheau5,6, Luis Teixeira2,7, Jacqueline Lehmann-Che1,2, Fatiha A. Bouhidel5, Pascal Merlet8, Marc Espié2,7, Matthieu Resche-Rigon3,4, Christos Sotiriou9 and David Groheux2,8
1Molecular Oncology Unit, Saint-Louis Hospital, Paris, France
2University Paris-Diderot, Sorbonne Paris Cité, INSERM/CNRS UMR944/7212, Paris, France
3Department of Biostatistics, Saint-Louis Hospital, Paris, France
4University Paris-Diderot, Sorbonne Paris Cité, INSERM UMR 1153 ECSTRA team, Paris, France
5Department of Pathology, Saint-Louis Hospital, Paris, France
6University Paris-Diderot, Sorbonne Paris Cité, INSERM UMR-S-1165, Paris, France
7Breast Diseases Unit, Saint-Louis Hospital, Paris, France
8Department of Nuclear Medicine, Saint-Louis Hospital, Paris, France
9Breast Cancer Translational Research Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
Patricia de Cremoux, email: firstname.lastname@example.org
Keywords: breast cancer; neoadjuvant chemotherapy; TP53 status; 18FDG-PET/CT; pathological complete response
Received: December 20, 2017 Accepted: February 26, 2018 Published: March 27, 2018
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.
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