Discovery of the on-off switch for triple negative breast cancer

Research by the Garvan Institute in Sydney Australia by Dr. Alex Swarbrick and Dr. Simon Junankar, et al has found the genetic on-off switch for triple negative breast cancer. Their research, published in Nature Communications, DOI: 10.103/ncomms7548, says they have been able to "switch" triple negative breast cancer (TNBC) to a treatable version by using ID4 to suppress the mammary stem cells. TNBC accounts for approximately 15% of all breast cancer and afflicts both men and women.

TNBCs lack the three receptors (estrogen, progesterone, and HER2) that make them responsive to targeted medication like Tamoxifen and aromatase inhibitors.

They found that TNBCs are diverse. Some types have prospects as good as other forms of BC whereas others are difficult to impossible to successfully treat. TNBC can be categorized as two distinct diseases which the researchers believe have different origins. One form of TNBC is enriched in stem cells. The research is not finalized but Swarbrick says if they are successful in switching TNBC to estrogen-positive BC the disease could be successfully treated.

ID4 gene is produced at high levels in roughly half of all triple negative breast cancers says Dr. Swarbrick. These cancers have a poor prognosis. Those with no stem cell involvement have a higher treatment success. High levels of ID4 are produced by roughly half of all TNBCs.

"Stem cells share similar traits to cancer cells in that they both have a long live, are resistant to treatment and have an unlimited capacity to divide." Judy Motti, TechTimes, March 29, 2015.

Their research based on blocking ID4 demonstrated that the tumor cells stopped dividing. When the ID4 gene is suppressed, estrogen receptors are switched on in the tumors, possibly converting them to the very treatable estrogen receptor-positive BC types which can be treated with Tamoxifen.

According to an article by Michael Slezak in New Scientist, April 4, 2015, other genes also play a role in whether a tumor is susceptible to therapy, so this might not be the whole story. Swarbrick’s team is now looking to see if the switched tumors respond to Tamoxifen.