A trial of chemotherapy and everolimus for HER2 breast cancer that had spread outside the breast (BOLERO 1)

Cancer type:

Breast cancer




Phase 3

This trial looked at chemotherapy and everolimus for breast cancer that was HER2 positive. It was for women:

  • whose breast cancer had grown into surrounding tissue (locally advanced) or had spread to elsewhere in the body
  • who had not yet had any treatment for advanced breast cancer

More about this trial

Some breast cancers have large amounts of a protein called HER2 Open a glossary itemon the surface of the cells. These cancers are HER2 positive and can be treated with a drug called trastuzumab (also known as Herceptin), which targets the HER2 protein.

It is usual to have Herceptin with chemotherapy. Paclitaxel is one of the chemotherapy drugs commonly used.

Sometimes a drug can stop working, even though the cancer responded to it at first. This is called resistance. In this trial, researchers wanted to find ways of treating breast cancer that had become resistant to Herceptin. They thought a drug called everolimus might help.

Everolimus is a type of biological therapy Open a glossary item. It is also known as Afinitor. It stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus can help to stop the cancer growing or may slow it down.

The aim of the trial was to see if having everolimus with Herceptin and paclitaxel helped women with HER2 positive breast cancer that had spread outside the breast.

Summary of results

The trial team found that having everolimus with Herceptin and paclitaxel was safe. But, it didn’t make a difference to how long it took for advanced HER2 positive breast cancer to get worse (progress).

719 women took part in the trial. They were put into 1 of 2 groups at random and were 2 times more likely to have everolimus than the dummy drug.

  • 480 had everolimus tablets every day
  • 239 had a dummy drug (placebo Open a glossary item) everyday

Everybody also had Herceptin and paclitaxel.

The study team followed the women up for an average of 3 ½ years. They looked at how long the women lived for after treatment without their cancer getting worse. This is called progression free survival. They found no difference between the 2 groups.

208 women had cancer that was HER2 positive but didn’t have receptors for oestrogen or progesterone. This is hormone receptor negative cancer.  The researchers looked at progression free survival in this sub group. They found this was:

  • 20.7 months in the group who had everolimus
  • 13 months in the group who had the dummy drug

The difference between the 2 groups is not statistically significant. This means it could have happened by chance. However the trial team think that these findings might be worth looking at in a future trial.

Everyone had problems with hair loss and diarrhoea. The more serious side effects of everolimus included:

The trial team found that having everolimus alongside Herceptin and paclitaxel wasn’t a useful treatment for advanced HER2 positive breast cancer.

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 Charles Swanton

Supported by

NIHR Clinical Research Network: Cancer

If you have questions about the trial please contact our cancer information nurses

Freephone 0808 800 4040

Last review date

CRUK internal database number:


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

Harriet wanted to try new treatments

Picture of Harriet

“I was keen to go on a clinical trial. I wanted to try new cancer treatments and hopefully help future generations.”

Last reviewed:

Rate this page:

No votes yet
Thank you!
We've recently made some changes to the site, tell us what you think