Computer-assisted image analysis of breast fine needle aspiration in a randomized chemoprevention trial of fenretinide vs. placebo in HRT users

BACKGROUND: Digital nuclear morphometric analysis can capture subtle differences along neoplastic progression. Studies showed different profiles from normal to cancer lesions. Our goal is to utilize this method as biomarker in chemoprevention trials. METHODS: Postmenopausal women were randomized to oral (CEE) or transdermal (E2) estrogen replacement therapy (ERT) in association with fenretinide or placebo. Ultrasound-guided fine needle aspiration (FNA) was performed at baseline and after 12 months in a subset of subjects. RESULTS: Ten samples were analyzed by karyometry. E2 compared with CEE increased nuclear area (p=0.01). A similar pattern was observed for other DNA content and chromatin texture features. Fenretinide vs. placebo, increased nuclear area and shape while decreased slope, peak and entropy. CONCLUSION: Preliminary results indicate that nuclear morphometry is feasible on FNA samples. ERT and fenretinide induced significant karyometric changes. These results support further investigation of this procedure as surrogate biomarker in chemoprevention trial