SMAD4 and breast cancer: In our screens, however, predicted loss-of-function mutations were identified in Smad4, Smad2, Tgfbr1, Tgfbr3, Bmpr1a, and Acvr2a. As TGFβ and BMP pathways can function in opposition to each other, additional studies will be required to determine how mutations in these genes function to promote breast cancer, as well as in what cell-of-origin, in cooperation with which other oncogenic pathway(s), and towards the development of which BC histotype(s).