Everolimus for Estrogen Receptor-negative Breast Cancer Prevention: A Journey Begun?

Tamoxifen, the prototypic medication for breast cancer prevention, was approved for this purpose by the FDA in 1998. Other drugs have been proven to be effective in the ensuing decades. But the two major limitations of these have become clear over time: a lack of protection against hormone receptor-negative breast cancer, and a profile of safety and tolerability that is unacceptable to the majority of women at increased breast cancer risk. Recent preclinical data on targeting of the key oncogenic pathway of PI3K/AKT/mTOR signaling with drugs such as rapamycin and everolimus are provocative. Their efficacy signal should be pursued with further research, but their safety and tolerability profiles remain a concern. See related article by Mazumdar et al., p. 791.