The addition of BH3 mimetics to standard tamoxifen treatment improved the effectiveness of hormone therapy in luminal B cancers, an aggressive subtype of estrogen receptor (ER)–positive breast cancer, recent research demonstrated.
The prosurvival protein BCL-2, which is frequently overexpressed in ER-positive breast cancer, helps cancer cells survive chemotherapy and other treatments. BH3 mimetics neutralize BCL-2, rendering cancer cells more vulnerable to destruction. Luminal B cancers in particular have high levels of BCL-2, according to information from the Walter and Eliza Hall Institute in Melbourne, Australia, where the recent study was carried out.
The Hall Institute investigators, including Professor Geoff Lindeman and others from the facility’s Breast Cancer Laboratory, found that a BH3 mimetic known as ABT-737 markedly enhanced tumor response to tamoxifen in animals implanted with human samples of luminal B cancers, as did the BCL-2 selective inhibitor ABT-199. The ABT-199 results demonstrated that BCL-2 is a crucial target, wrote the researchers in Cancer Cell (2013;24:120-129).
In the Hall Institute statement, Lindeman noted that in one case, a tumor disappeared completely after combination therapy, whereas standard treatment with tamoxifen alone showed only a partial and unsustained benefit. In addition, the BH3 mimetics were found to counteract the side effect of tamoxifen-induced endometrial hyperplasia, and also helped induce apoptosis (programmed death) of cancer cells.
Lindeman and colleagues hope that these findings will lead to clinical trials of BH3 mimetics for the treatment of ER-positive breast cancers. BH3 mimetics are already being tested in clinical trials for some types of leukemia.