A hierarchical prognostic model for risk stratification in patients with early breast cancer according to 18 F-fludeoxyglucose uptake and clinicopathological parameters

Abstract

This study was to investigate a hierarchical prognostic model using clinicopathological factors and ¹⁸ F-fludeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) for recurrence-free survival (RFS) in patients with early breast cancer who underwent surgery without neoadjuvant chemotherapy. A total of 524 patients with early breast cancer were included. The Cox proportional hazards model was used with clinicopathological variables and maximum standardized uptake value (SUVmax) on PET/CT. After classification and regression tree (CART) modeling, RFS curves were estimated using the Kaplan-Meier method and differences in each risk layer were assessed using the log-rank test. During a median follow-up of 46.2 months, 31 (5.9%) patients experienced recurrence. The CART model identified four risk layers: group 1 (SUVmax ≤6.75 and tumor size ≤2.0 cm); group 2 (SUVmax ≤6.75 and Luminal A [LumA] or TN tumor >2.0 cm); group 3 (SUVmax ≤6.75 and Luminal B [LumB] or human epidermal growth factor receptor 2 [HER2]-enriched] tumor >2.0 cm); group 4 (SUVmax >6.75). Five-year RFS was as follows: 95.9% (group 1), 98% (group 2), 82.8% (group 3), and 85.4% (group 4). Group 3 or group 4 showed worse prognosis than group 1 or group 2 (group 1 vs. group 3: P = 0.040; group 1 vs. group 4: P < 0.001; group 2 vs. group 3: P = 0.016; group 2 vs. group 4: P < 0.001). High SUVmax (>6.75) in primary breast cancer was an independent factor for poor RFS. In patients with low SUVmax, LumB or HER2-enriched tumor >2 cm was also prognostic for poor RFS, similar to high SUVmax.

Keywords: 18F-FDG PET/CT; classification and regression tree modeling; early breast cancer; recurrence-free survival; risk model.

Figure 1

Flow diagram of patients included in the current study. FDG PET/CT indicates ¹⁸F‐fludeoxyglucose positron emission tomography/computed tomography; IHC immunohistochemistry.

Figure 2

Representative ¹⁸F‐fludeoxyglucose positron emission tomography/computed tomography images of patients in each molecular subtype. (A) Luminal A subtype (SUVmax = 3.30, tumor size = 1.8 cm); (B) Luminal B subtype (SUVmax = 5.86, tumor size = 2.0 cm); (C) human epidermal growth factor receptor 2‐enriched subtype (SUVmax = 6.80, tumor size = 1.9 cm); (D) triple negative subtype (SUVmax = 9.50, tumor size = 1.8 cm). SUVmax indicates maximum standardized uptake value.

Figure 3

Classification and regression tree analyses to identify synergistic/antagonistic associations between prognostic factors. Square boxes indicate, respectively, intermediate and terminal subsets of patients defined by the sequential splitting process. There are four terminal risk groups. The numbers after molecular subtype are the number of recurrences of the total number of patient in each subtype. Cox proportional hazard model calculated HRs of each group. * = statistically significant difference for pairwise comparison using log‐rank test. HER2 = human epidermal growth factor receptor 2; LumA = Luminal A; LumB = Luminal B; TN = triple negative.