대한유방검진의학회

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Purpose: The purpose of this study is to evaluate the relationship between histological findings of mammary gland development and risk of breast cancer in BRCA1 mutant mice. Materials and Methods: Five BRCA1 mutant mice and five non-mutant FVB/NJ mice were used for each of the 1-month-old (pubertal), 3-month-old (fertile) and 8-month-old (menopausal) group and the entire fourth mammary tissue was taken at each step. In addition, breast cancer development was assessed in 8 months old BRCA1 mutant mice (15 mice), and classified into tumor-bearing groups (11 mice) and tumor-free groups (4 mice) and normal mammary tissues were collected. In the analysis of mammary gland tissues, only epithelial cells were carminestained, and the number of alveolar buds, epithelial density, and mammary duct elongation were measured using image analysis programs. The difference between the two groups was assessed by the paired T-test statistical method. Results: One-month-old BRCA1 mutant mice compared with controls showed a higher number of alveolar buds (3.6 ± 0.7 vs. 0.8 ± 0.4, P=0.0068), epithelial density (43.9 ± 0.5% vs. 27.8 ±3.5%, P=0.0017) and mammary duct elongation (9.5 ± 0.6 mm vs. 7.0 ± 0.4 mm, P=0.0102). However, there was no difference in the 3 months and 8 months old group. In BRCA1 mutant mice, the tumor-bearing group was significantly higher in the number of alveolar buds (59.2 ±2.0 vs. 41.2 ± 2.1, P=0.0002) and epithelial density (68.6 ± 2.4% vs. 43.7 ± 1.7%, P<0.0001) compared to the tumor-free group. The mammary duct elongation was not different (21.8 ± 0.6mm vs. 22.6 ± 0.6 mm, P=0.3662). Conclusion: BRCA1 mutant mice had early pubertal mammary gland development and delayed involution of the lobule and epithelial cells of the mammary tissue was associated with breast cancer. The above results suggest that mutations in breast cancer predisposition genes such as BRCA1 may be a cause of premature mammary gland development and will help to understand the imaging findings and tissue composition of mammary gland associated with high risk of breast cancer.
Key Words: BRCA1; Transgenic mice; Mammary gland; Mouse models