Tumor metabolism assessed by FDG-PET/CT and tumor proliferation assessed by genomic grade index to predict response to neoadjuvant chemotherapy in triple negative breast cancer
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Survival is increased when pathological complete response (pCR) is reached after neoadjuvant chemotherapy (NAC), especially in triple-negative breast cancer (TNBC) patients. Positron emission tomography/computed tomography (PET/CT) with 18F-fluorodeoxyglucose (FDG) and the genomic grade index (GGI), each separately, showed good potential to predict pCR. Our study was designed to evaluate the predictive value for the therapeutic response of a combination of parameters based on FDG-PET, histoclinical features and molecular markers of proliferation.
Molecular parameters were measured on pre-treatment biopsy. Tumor metabolic activity was measured using two PET/CT scans, one before and one after 2 cycles of NAC. The pCR was determined on specimen after NAC. Event-free survival (EFS) was estimated using the Kaplan Meier method.
Of 55 TNBC patients, 19 (35%) reached pCR after NAC. Tumor grade and Ki67 were not associated with pCR whereas GGI (P = 0.04) and its component KPNA2 (P = 0.04) showed a predictive value. The change of FDG uptake between PET1 and PET2 (ΔSUVmax) was highly associated with pCR (P = 0.0001) but the absolute value of baseline SUVmax was not (P = 0.11). However, the AUC of pCR prediction increased from 0.63 to 0.76 when baseline SUVmax was combined with the GGI (P = 0.016). The only two parameters associated with EFS were ΔSUVmax (P = 0.048) and pathological response (P = 0.014).
The early tumor metabolic change during NAC is a powerful parameter to predict pCR and outcome in TNBC patients. The GGI, determined on pretreatment biopsy, is also predictive of pCR and the combination GGI and baseline SUVmax improves the prediction.
KeywordsFDG-PET/CT Genomic grade index Triple negative breast cancer Neoadjuvant chemotherapy Pathological complete response Event free survival
We thank Mrs. E Wittmer for her excellent technical expertise for the realization of all molecular analysis. We thank all the staff of the departments of Nuclear Medicine, of Medical Oncology, of Surgical Oncology and of radiation therapy of Biochemistry and of Pathology, and especially, Dr. Bourstyn, Dr. Cahen-Doidy, Dr. Cuvier, Dr. Giacchetti, Dr. Hennequin, Dr. Lemarignier, Dr. de Rocquancourt, Dr. Vercellino, who participated to the management of the patients. We thank L Someil, K Aboudou and L Culine from the CIRCO for their help for CRF completion.
This study was supported by an academic grant (“Translational research in oncology” INCa-DHOS-5697).
Compliance with ethical standards
Conflicts of interest
All the authors declared no conflicts of interest.
Research involving human participants and/or animals
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
For this retrospective study, written consent was not required.
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