Abstract 2286: Spontaneous mammary cancer development in genetically engineered mice with only one copy of Brca1 disrupted in combination with Trp53 haploinsufficiency

Background: Women carrying one mutated copy of BRCA1 are disposed to developing breast cancer. BRCA1-mutation-related cancers often harbor TRP53 mutations. Previously established genetically engineered mouse (GEM) models with spontaneous mammary cancer development have both copies of Brca1 disrupted in combination with Trp53 haploinsufficiency. Here we characterized cancer development in GEM with only one copy of Brca1 disrupted in mammary epithelial cells using Cre-Lox technology in combination with germ-line Trp53 haploinsufficiency. Methods: From our Brca1 f11fT11/MMTV-Cre/Trp53+/− breeding program we noted mammary cancer development in female Brca1 f11/WT11/MMTV-Cre/Trp53+/− mice. The time-course of mammary hyperplasia and cancer development was characterized in these mice. Mice were euthanized at age 6 months (n = 9) or when the largest tumor reached 1 cm 3 or at 12 months if no tumor developed (n = 12). Cancers were resected, inguinal mammary glands processed for histology and thoracic mammary glands flash frozen or processed for primary cell culture. Hyperplastic alveolar nodules (HANs) and branching patterns were detected using inguinal mammary gland whole mounts. Histology was read on HE 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2286. doi:10.1158/1538-7445.AM2015-2286