Cancer Research UK scientists have discovered why a sub group of oestrogen-receptor-negative breast cancer patients could benefit from prostate cancer treatments which target the cell’s androgen receptor – a key driver of prostate cancer, according to research published in The EMBO Journal today.
The team at Cancer Research UK’s Cambridge Research Institute has shown in cancer cells that androgen receptors trigger breast cancer cell growth in oestrogen- receptor-negative molecular apocrine tumours. This group makes up five per cent of all breast cancers.
Oestrogen-receptor-negative breast cancer can be difficult to treat as tumours do not respond to hormone treatments such as tamoxifen or aromatase inhibitors. In oestrogen-positive breast cancer, the oestrogen receptor acts as a switch, which is ‘turned on’ by oestrogen to fuel the disease.
The androgen receptor is similarly fuelled by the androgen hormone, testosterone, to drive prostate cancer.
But the scientists discovered in oestrogen-receptor-negative molecular apocrine breast cancer, that androgen receptors can also switch on genes usually switched on by the oestrogen receptor, which control cell growth – fuelling breast cancer.
This involves a protein called FoxA1 which ‘directs’ the androgen receptor to switch on genes that are normally used by the oestrogen receptor.
It is not yet known whether in this disease the androgen receptor is fuelled by testosterone, oestrogen or whether the androgen receptor somehow triggers breast cancer independently – without the presence of a hormone.
Lead author, Dr Ian Mills, at Cancer Research UK’s Cambridge Research Institute, said: “This important discovery suggests that patients with a type of oestrogen-receptor-negative breast cancer may potentially benefit from therapies given to prostate cancer patients, which could transform treatment for this patient group in the future.
“But at the moment this laboratory research is still at an early stage. We don’t know if oestrogen or hormones from the androgen family such as testosterone also have a role to play in fuelling the disease in this patient group. The challenge is to pin down these answers through further laboratory and clinical research.”
Breast cancer is the most common cancer in UK women with around 48,000 new cases detected each year. Eight out of 10 women now survive breast cancer for more than five years, compared with five out of 10 women in the 1970s.
Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “This intriguing study reveals a completely new route by which a type of oestrogen-receptor-negative breast cancer can develop. Prostate cancer depends on the androgen receptor for growth so it’s a great surprise that a type of breast cancer might also be fuelled by this protein.
“Our work has underpinned today’s treatments for breast cancer and helped save many thousands of lives. But there is more to be done. Patients with oestrogen-receptor-negative breast cancer have a narrow selection of treatments available, because these tumours lack the protein receptors targeted by important drugs such as tamoxifen and Herceptin. But we hope these findings will accelerate research to increase the range of therapies available for this group.”
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Robinson et al. Androgen Receptor driven transcription in molecular apocrine breast cancer is mediated by FoxA1. The EMBO Journal.
Receptors are proteins that some cancer cells have. When specific substances in your body attach to specific receptors, they trigger a reaction in the cell. When they are triggered, oestrogen receptors, progesterone receptors and Her2 receptors can tell breast cancer cells to grow. Oestrogen attaches to oestrogen receptors. Progesterone attaches to progesterone receptors. And Her2 attaches to Her2 receptors. Some breast cancers have one or more of these receptors.
Around 25 to 30 out of every 100 breast cancers are oestrogen receptor negative. Some commonly-used breast cancer treatments such as hormone therapy do not work for oestrogen-receptor-negative breast cancer. This treatment requires the presence of the oestrogen receptor to work.
In healthy, non-cancerous tissues the androgen receptor is predominantly present in the prostate with very low levels in some other tissues. In cancers the highest levels are found in prostate tumours with evidence emerging of increased presence in subsets of cancers at other organ sites.