Combined ¹⁸F-FDG and ¹⁸F-Alfatide II PET May Predict Luminal B (HER2 Negative) Subtype and Nonluminal Subtype of Invasive Breast Cancer

Abstract

Noninvasive PET molecular imaging using radiopharmaceuticals is important to classify breast cancer in the clinic. The aim of this study was to investigate the combination of 18F-FDG and 18F-Alfatide II for predicting molecular subtypes of invasive breast cancer. Forty-four female patients with clinically suspected breast cancer were recruited and underwent 18F-FDG and 18F-Alfatide II PET/CT within a week. Tracer uptake in breast lesions was assessed using the maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and SUVmax ratio of 18F-FDG to 18F-Alfatide II (FAR). Invasive breast cancer lesions were further classified as luminal A subtype, luminal B subtype, human epidermal growth factor receptor-2 (HER2) overexpressing subtype, and triple negative subtype according to the expression of the estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki-67. Among 44 patients, 35 patients were pathologically diagnosed with invasive breast cancer. The SUVmax and SUVmean of 18F-FDG were significantly higher in the ER-negative group than those in the ER-positive group, as well as in the PR-negative group than those in the PR-positive group. However, the SUVmax and SUVmean of 18F-Alfatide II were higher in the ER-positive group and the PR-positive group. By combining 18F-FDG and 18F-Alfatide II, the FAR was lower in the ER-positive group and the PR-positive group. The HER2 overexpressing subtype showed the highest SUVmax and SUVmean for 18F-FDG while the luminal B (HER2 negative) subtype revealed the lowest values. The luminal B (HER2 negative) subtype showed the highest 18F-Alfatide II SUVmax, while the triple negative subtype showed the lowest 18F-Alfatide II SUVmax. The FAR was the lowest in the luminal B (HER2 negative) subtype and much higher in the HER2 overexpressing and triple negative subtypes. FAR less than 1 predicted the luminal B (HER2 negative) subtype with high specificity (93.1%) and NPV (90%). FAR greater than 3 predicted the HER2 overexpressing subtype and triple negative subtype (namely, the nonluminal subtype) with very high specificity (100%) and PPV (100%). In summary, FAR, the combined PET parameter of 18F-FDG and 18F-Alfatide II, can be used to predict molecular subtypes of invasive breast cancer, especially for the luminal B (HER2 negative) subtype and the nonluminal subtype.