Metastatic breast cancer gene can turn itself on and off

Metastatic breast cancer is both aggressive and difficult to treat. Researchers have been searching within human genes to find new ways to treat this cancer—and a team at Massachusetts General Hospital Cancer Center have made a discovery that may impact how the cancer is treated in the future.

Led by Daniel Haber, MD, PhD, a team of researchers studied circulating tumor cells (CTCs) to find a unique gene expression in metastatic breast cancer that may be the main factor the disease’s progression and why it becomes resistant to treatments.

The study used the CTC-iChip, a device that collects CTCs from women, to examine cancer tumors that have estrogen receptor genes (ER+) but did not have the HER2 gene (HER2-). Researchers found that CTCs were comprised of both ER+/HER- and ER+/HER2+ cells.

Further exploration of CTCs brought about the finding of the interconversion of HER2 gene expression. Researchers found that ER+/HER2- cells could randomly change into ER+/HER2+ cells and then convert back. The two different tumor cells relied on different molecular signaling pathways, making them susceptible to different cancer treatment drugs.

The on-and-off nature of the HER2 gene led researchers to conclude the separate signaling pathways must both be shut off to stop the growth of tumor cells. More experimentation further proved that treatment with both chemotherapy and cancer drugs stopped the NOTCH1 signaling pathways, leading to the stoppage of tumor cell growth with ER+/HER2- and HER2+ gene expressions.

"Although more research is needed to uncover why HER2 has this dynamic on-and-off expression, these insights from our research are a positive development for a new treatment approach," said Haber.