A trial looking at low dose oestrogen to treat advanced breast cancer after menopause

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Cancer type:

Breast cancer
Secondary cancers

Status:

Results

Phase:

Phase 2
This trial looked at a drug called oestradiol to treat advanced breast cancer. It was for women:
  • who’d had a type of hormone therapy drug called an aromatase inhibitor, but it had stopped working 
  • whose breast cancer was hormone receptor positive Open a glossary item

More about this trial

Doctors used to use oestrogen Open a glossary item to treat women with breast cancer after menopause Open a glossary item. This is because oestrogen can kill breast cancer cells if they haven’t been exposed to high levels before. And it worked because the body stops making most of its oestrogen at menopause. But high doses of oestrogen have unpleasant side effects. So doctors started using drugs like tamoxifen, or aromatase inhibitors to treat breast cancer instead.
 
Aromatase inhibitors Open a glossary item are types of hormone therapy drugs. They include:
  • anastrozole
  • letrozole 
  • exemestane 
These drugs lower the amount of oestrogen in the blood. But sometimes they stop working. So, researchers wanted to find a way of treating advanced breast cancer that has become resistant to hormone therapies. 
 
We know from research that doctors may be able to use a lower dose of oestrogen than they used to use to kill breast cancer cells. Having an aromatase inhibitor after the menopause means the oestrogen levels are much lower than normal menopause levels. So, the amount of oestrogen you need to affect the cancer may be lower too and this would be likely to reduce side effects. The low dose oestrogen treatment used in this trial is called oestradiol. 
 
The aim of the trial was to:
  • see if low dose oestrogen worked for advanced breast cancer that had become resistant to aromatase inhibitors
  • learn more about the side effects

Summary of results

The trial team found that low dose oestrogen worked for some women in this small trial. And the side effects were acceptable, apart from vaginal bleeding. 
 
This phase 2 trial took place in the UK. The researchers published the results in 2015. 
 
The trial team found it was difficult to find enough women to take part, so the trial closed earlier than planned. This was mainly because women didn’t want to take low dose oestrogen as their previous treatment was directed at reducing oestrogen concentrations. 
 
Treatment
21 women joined the trial and the researchers had the results for 19. Treatment was in 3 stages, as follows:
  • low dose oestrogen (oestradiol)
  • high dose oestrogen
  • an aromatase inhibitor 
Everyone took low dose oestrogen until it stopped working. They then had the option to try high dose oestrogen if their doctor thought it could work. 
 
They then restarted the aromatase inhibitor they were taking before the trial if either dose of oestrogen worked. This is because the oestrogen may have made the cancer sensitive to aromatase inhibitors again.
 
Results 
The trial team looked at how well low dose oestrogen (oestradiol) worked. They found in:
  • 5 women treatment worked and the cancer stayed stable
  • 14 women the cancer got worse
On average, the cancer stayed the same for about 17 months. 
 
3 out of 5 women went on to have high dose oestrogen when oestradiol stopped working. Of those 3 women, the cancer shrank significantly in 1. This is called having a partial response to treatment.  
 
Of the 5 women who had oestradiol that worked, 4 restarted their aromatase inhibitor. They looked at how well this worked. 
 
In:
  • 3 women the cancer remained stable for at least 6 months
  • 1 woman the cancer shrank significantly
The trial team say that low dose oestrogen seemed to work best in women whose first aromatase inhibitor hormone therapy had also worked well and controlled the cancer for a long time. 
 
Side effects
The most common side effects of oestradiol were:
  • feeling or being sick
  • tiredness (fatigue)
  • breast pain
  • headache
  • vaginal bleeding 
8 women had vaginal bleeding, and this was the most common side effect. 4 women had to stop treatment because of side effects. 
 
Conclusion 
The trial team concluded that lose dose oestrogen worked for some women with advanced breast cancer. And giving an aromatase inhibitor afterwards works and shows that the cancer can become sensitive to them again. But this was a small trial and although the side effects were acceptable, vaginal bleeding was a problem. 
 
We have based this summary on information from the research team. The information they sent us has been reviewed by independent specialists (peer reviewed Open a glossary item) and published in a medical journal. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.

Recruitment start:

Recruitment end:

How to join a clinical trial

Please note: In order to join a trial you will need to discuss it with your doctor, unless otherwise specified.

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Chief Investigator

Dr Sacha Howell

Supported by

Bayer-Schering
Experimental Cancer Medicine Centre (ECMC)
The Christie NHS Foundation Trust

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Last review date

CRUK internal database number:

1255

Please note - unless we state otherwise in the summary, you need to talk to your doctor about joining a trial.

Charlie took part in a trial to try new treatments

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“I think it’s really important that people keep signing up to these type of trials to push research forward.”

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