Responsiveness of Brca1 and Trp53 Deficiency-Induced Mammary Preneoplasia to Selective Estrogen Modulators versus an Aromatase Inhibitor in Mus musculus

An intervention study initiated at age 4 months compared the impact of tamoxifen (25 mg), raloxifene (22.5 mg), and letrozole (2.5 mg) administered by 60-day release subcutaneous pellet on mammary preneoplasia prevalence at age 6 months in conditional genetically engineered mouse models with different Breast cancer 1 (Brca1) gene dosages targeted to mammary epithelial cells and germline Tumor protein P53 (Trp53) haploinsufficiency (10–16/cohort). The proportion of unexposed control mice demonstrating mammary preneoplasia at age 6 months was highest in Brca1fl11/fl11/Cre/p53–/+ (54%) mice followed by Brca1WT/fl11/Cre/p53–/+ mice (30%). By age 12 months, invasive mammary cancers appeared in 80% of Brca1fl11/fl11/Cre/p53–/+and 42% of Brca1WT/fl11/Cre/p53–/+control unexposed mice. The spectrum of cancer histology was similar in both models without somatic mutation of the nongenetically engineered Brca1, Trp53, Brca2, or Death-associated protein kinase 3 (Dapk3) alleles. Two-month exposure to tamoxifen, raloxifene, and letrozole significantly reduced estrogen-mediated tertiary branching by 65%, 71%, and 78%, respectively, in Brca1fl11/fl11/Cre/p53–/+mice at age 6 months. However, only letrozole significantly reduced hyperplastic alveolar nodules (HAN) prevalence (by 52%) and number (by 30%) and invasive cancer appeared despite tamoxifen exposure. In contrast, tamoxifen significantly reduced HAN number by 95% in Brca1WT/fl11/Cre/p53–/+ mice...
Source: Cancer Prevention Research - Category: Cancer & Oncology Authors: Tags: Research Articles Source Type: research