The Value of Semiquantitative Parameters Derived from (18)F-FDG PET/CT for Predicting Response to Neoadjuvant Chemotherapy in a Cohort of Patients with Different Molecular Subtypes of Breast Cancer

SIMPLE SUMMARY: The aim of this study was to investigate whether baseline [(18)F]Fluorodeoxyglucose ([(18)F]FDG) positron emission computed tomography/computed tomography (PET/CT) could predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) and survival outcomes in patients affected by different molecular subtypes of breast cancer (BC). Semiquantitative parameters, extracted from baseline [(18)F]FDG PET/CT, seem to be promising in the prediction of response to NAC in Luminal B and Luminal B + HER-2 patients and in the survival prediction of triple negative BC patients achieving pCR after NAC. PET/CT scan with advanced parameter analysis could carve out a synergic role, together with other imaging tools, for a more accurate evaluation of these patients at diagnosis. ABSTRACT: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is a strong prognostic factor in breast cancer (BC). The aim of this study was to investigate whether semiquantitative parameters derived from baseline [(18)F]Fluorodeoxyglucose ([(18)F]FDG) positron emission computed tomography/computed tomography (PET/CT) could predict pCR after NAC and survival outcomes in patients affected by different molecular subtypes of BC. We retrospectively retrieved patients from the databases of two Italian hospitals (Centre A: University Hospital of Ferrara; Centre B: University of Padua) meeting the following inclusion criteria: (1) diagnosis of BC; (2) history of NAC; (3) baseline [(18)F]FDG PET/CT performed before the first cycle of NAC; (4) available follow-up data (response after NAC and survival information). For each [(18)F]FDG PET/CT scan, semiquantitative parameters (SUVmax, SUVmean, MTV and TLG) related to the primary tumor (B), to the reference lesion for both axillary (N) and distant lymph node (DN), and to the whole-body burden of disease (WB) were evaluated. Patients enrolled were 133: 34 from centre A and 99 from centre B. Patients’ molecular subtypes were: 9 luminal A, 49 luminal B, 33 luminal B + HER-2, 10 HER-2 enriched, and 32 triple negative (TNBC). Luminal A and HER-2 enriched BC patients were excluded from the analysis due to the small sample size. pCR after NAC was achieved in 47 patients (41.2%). [(18)F]FDG PET/CT detected the primary tumor in 98.3% of patients and lymph node metastases were more frequently detected in Luminal B subgroup. Among Luminal B patients, median SUVmean_B values were significantly higher (p = 0.027) in responders (7.06 ± 5.9) vs. non-responders (4.4 ± 2.1) to NAC. Luminal B + HER-2 non-responders showed a statistically significantly higher median MTV_B (7.3 ± 4.2 cm(3) vs. 3.5 ± 2.5 cm(3); p = 0.003) and TLG_B (36.5 ± 24.9 vs. 18.9 ± 17.7; p = 0.025) than responders at baseline [(18)F]FDG PET/CT. None of the semiquantitative parameters predicted pCR after NAC in TNBC patients. However, among TNBC patients who achieved pCR after NAC, 4 volumetric parameters (MTV_B, TLG_B, MTV_WB and TLG_WB) were significantly higher in patients dead at follow-up. If confirmed in further studies, these results could open up a widespread use of [(18)F]FDG PET/CT as a baseline predictor of response to NAC in luminal B and luminal B + HER-2 patients and as a prognostic tool in TNBC.