Overexpression of the R subunits of PKA (in particular, RI) is associated with high proliferation in normal breast, malignant transformation in the breast, poor prognosis in established breast cancer, and resistance to antiestrogens. These data, together with the observation that successful antiestrogen therapy is associated with reduced expression of RI mRNA, suggest that targeting R subunits is an appropriate therapeutic strategy for breast cancer. Initial experimental results, using antisense RI oligonucleotides, are promising in terms of reducing the growth rate of breast cancer cells and xenografts. While clinical trials designed to target RI subunits have yet to be established (and interventions as preventative measures are even more distant), the concept of these approaches to prevent and treat breast cancer should be developed and exploited.