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

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 (SUV_max), mean standardized uptake value (SUV_mean), and SUV_max 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 SUV_max and SUV_mean 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 SUV_max and SUV_mean 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 SUV_max and SUV_mean 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 SUV_max, while the triple negative subtype showed the lowest ¹⁸F-Alfatide II SUV_max. 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.