Differential efatutazone's impact on mammary neoplasia dependent upon Brca1 dose

Peroxisome proliferator-activated receptor gamma and BRCA1

“…In summary, it is not yet clear whether or not interactions between PPARG and BRCA1 modify the impact of a PPARgamma agonist used as a breast cancer chemopreventive. The PPARg agonist efatutazone is effective in significantly reducing mammary hyperplasia in mice with targeted deletion of Brca1 exon 11 in mammary epithelial cells, but there is no profound effect on invasive cancer incidence (Nakles et al 2013, Alothman et al 2018. However, preservation of one intact Brca1 allele is sufficient to significantly improve the preventive response.…”

“…In addition, pharmacological intervention is initiated at different time points relative to cancer initiation and study durations are mixed. Positive impacts provide support for the principle of PPARG agonist chemoprevention (Kocdor et al 2009, Li & Brown 2009, McCormick et al 2015, Ory et al 2018 but when significant effects are limited to hyperplasia and/or preneoplasia, alterations in cancer histology and/or mean tumor volume, there is less enthusiasm (Borbath et al 2007, Wu et al 2008, Skelhorne-Gross et al 2012, Nakles et al 2013, Bojková et al 2016, Alothman et al 2018. Occasional published studies report no effect at all (Yee et al 2005).…”