A potential new target for treating the most common form of breast cancer has been discovered by an international team of scientists.

Although it will be some years before a treatment based on the new findings could be ready, it could provide an alternative therapy for patients who have developed resistance to existing breast cancer drugs.

Led by scientists from the Faculty of Medicine at Imperial College London, the team has discovered that an enzyme called APOBEC3B (A3B) plays a key role in enabling the most common form of breast cancer to grow.

The research, funded by Cancer Research UK and Breast Cancer Now, is published today in Cell Reports.

The researchers looked at survival rates amongst patients with this form of the disease – known as estrogen receptor positive (ER+) breast cancer.  They found that patients with ER+ breast cancer who also had high levels of A3B did not live as long as those with normal levels of the enzyme.

When the team blocked the activity of A3B in mouse models of the disease, this reduced the growth of the tumour.  The team knocked out A3B using a technology that can’t currently be directly translated into a treatment, so work is already underway to develop drugs able to stop the enzyme’s activity.

In ER+ breast cancer, the estrogen receptor protein (ER) causes certain genes to work overtime, making the cancer cells proliferate faster and so promoting tumour growth. ER can only do this in the presence of the hormone estrogen, which is why existing breast cancer drugs either block estrogen production (aromatase inhibitors such as Arimidex or Aromasin) or block the ER protein directly (Tamoxifen).

Lead author Professor Simak Ali, from Imperial’s Department of Surgery and Cancer said:  “Current treatments for ER+ breast cancer, which affects over 70 percent of patients, are very effective. But a considerable proportion of patients will develop resistance and each time that happens, their remission period is shorter. A treatment based on A3B would provide another route for patients resistant to either ER or aromatase inhibitors.”

Tumours from the treated mice were found to contain lower levels of the genes targeted by the ER protein. When the team then looked at what was happening within breast cancer cells, they saw that ER carries A3B to the ER target genes, where A3B causes changes to the DNA, triggering possible mutations and enabling their overexpression.

A3B is known to be a common link between the genetic mutations that take place in breast cancer and in ovarian and lung cancer. So it is also possible that the team’s work on A3B could lead to new treatments for these cancers as well.

“We don’t know yet if the ER protein interacts with A3B in the same way in ovarian and lung cancer as it does for breast cancer,” said Professor Ali. “If that proves to be the case, it’s possible that a treatment like Tamoxifen might be effective against these diseases too. It might also mean that, if we are able to develop a treatment that blocks A3B, it might work as a therapy for a number of cancers, not just breast cancer.”

The study involved researchers from the CRUK Cambridge Research Institute, the Netherlands Cancer Institute in Amsterdam, Semmelweis University in Budapest and the University of Dundee.

Reference: "APOBEC3B Mediated Cytidine Deamination is Required for Estrogen Receptor Action in Breast Cancer" Cell Reports, published online 24 September 2015