New insight into ER+ breast cancer

The estrogen response of breast tumor cells is variable and not on a 90-minute cycle like previous studies suggested.
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Image credit: Miguel Á. Padriñán (CC0)

Breast cancer is the most common type of cancer worldwide. The hormone estrogen drives the growth of 70% of breast cancer tumors. This form of breast cancer is called estrogen receptor positive (ER+) breast cancer. In the early 2000s, several scientists found that some genes in ER+ breast cancers turn on and off in 90-minute cycles. Moreover, when the estrogen receptor binds to the DNA in the nucleus of a cell, it activates nearby genes causing the tumor cells to grow and divide.

Learning more about how cancer cells respond to estrogen is very important. Many cancer drugs block estrogen to stop its tumor growth promoting effects. But the initial studies of estrogens effects were only able to look at how estrogen affected a small number of genes. Newer genome sequencing technologies allow scientists to study the effects of estrogen on more genes and provide more detailed information.

Using these cutting-edge technologies, Holding et al. show that the 90-minute cycles found in the previous studies are likely artefacts of older techniques and lacking controls. The new experiments used a newer technique called parallel factor ChIP-seq to look at how all genes respond to the estrogen receptor. Then, Holding et al. reanalyzed data published in the previous studies and found that they were often contradictory and inconsistent.

None of the genes – not even the ones looked at in earlier studies – were expressed in 90-minute cycles like the previous studies suggested. Instead, the expression of the genes was variable, which may make the cell even more responsive to estrogen. The previous reports of the 90-minute cycles are most likely explained by a bias of the human eye of finding patterns in a highly variable process that do not hold up to statistical analysis.

Better understanding how estrogen influences genes and cell growth is essential to developing better treatments for ER+ breast cancer. This includes ruling out ideas that may be incorrect or misleading. These findings help resolve why not all studies have found estrogen receptor driven cycles of gene expression, and will provide researchers with a better foundation for future studies.