Crossing MMTV-PyMT males with females from the genetically divergent MOLF/EiJ inbred strain, followed by crossing hybrid MMTV-PyMT males to FVB/NJ females, predisposed MMTV-PyMT N2 offspring to mammary tumors with gene signatures resembling estrogen receptor negative (ER-) breast cancers, thus tilting the model towards an aggressive form of breast cancer [6]. The gene discussed is ESR1; the disease is breast cancer.