ESR1 and ductal breast carcinoma in situ: Genetically engineered ERα over-expression in mammary epithelial cells in transgenic mice leads to development of ductal hyperplasia and ductal carcinoma in situ (DCIS) lesions by four months of age [31], hyperplastic alveolar nodules (HANs) by eight months of age [32], and both ERα positive and ERα negative invasive mammary cancers by 12 months of age following single-dose treatment with the chemical carcinogen 12-dimethylbenz[a]anthracene (DMBA) [33].