PIK3CA and breast cancer: Furthermore, the effects of R-RAS2 expression were linked to the activation of the PI3K/Akt pathway by this GTPase, independently of the mutational status of KRAS. Moreover, a polymorphism in the RRAS2 promoter is associated with an unfavorable tamoxifen treatment outcome [14] and, conversely, silencing the RRAS2 gene enhances the tamoxifen sensitivity of a BC cell line [15].