RAS or RAF mutations occur in 47% of metastatic melanoma cases,46 and KRAS mutations are found in ~25%–27% of human lung adenocarcinomas.47 RAS, RAF, and MEK mutations, however, are rarely observed—at rates of ~1%–6%—in breast cancer.48 Thus, it is plausible that in breast cancers, ERK activation may proceed via persistent upstream signaling rather than constitutively active RAS, RAF, or MEK mutants. This evidence concerns the gene KRAS and breast cancer.