As the Pink Hope community knows all too well, women who carry the BRCA 1 gene mutation have a high risk of developing breast cancer at some point in their lifetime. Options for reducing that risk are limited, with the most effective being bilateral mastectomies.
However, if we could prevent breast cancer in these women in the first place, without them having to resort to such distressing and invasive surgery to lower their risk, that would allow them to live with less worry and less fear.
A new international trial, called the BRCA P trial, is aiming to do just that – and they need volunteers. We asked medical oncologist Dr Nicholas Zdenkowski, who is involved in the trial, to tell us a little more about it.
To start with, Dr Zdenkowski, could you explain a little bit of the background of this trial?
“Sure, the BRCA-P trial is evaluating a medication that we have preliminary evidence to show targets precancerous cells (that eventually develop into cancer) and stop them from progressing to cancer.”
Are there any medications available that do something similar?
“Yes, there’s a couple of medications that are effective in doing this already, but they aren’t widely used. Tamoxifen and Anastrozole can help with the estrogen positive cancers in high risk individuals, but lot of women don’t like taking these medications because they are not highly effective and there are side effects. Also, BRCA1 carrying women are more likely to develop a triple negative breast cancer, which is not something that Tamoxifen has been shown to help to prevent. So, we had to look at other medications and there’s been some laboratory studies that have shown that via a complicated pathway, inhibition of something called RANK ligand, can prevent the development of breast cancer in BRCA1 type precancerous cells in the laboratory.”
What is RANK ligand?
“RANK ligand is a circulating factor in the blood and within bone, and we’ve got a medication called Denosumab, which is a RANK ligand inhibitor. Currently, it’s being used for a couple of different situations. Firstly, to treat osteoporosis and to strengthen bones by stopping the bone from becoming thinner or less dense. And, secondly, it’s also used for people with cancer and bone lesions from metastatic breast cancer and prostate cancer as it helps to slow down or prevent the development of new bone lesions in those patients. So, it’s a fairly widely available medication.”
And this trial looks at that drug in the treatment of breast cancer?
“Yes, so based on the preclinical laboratory work done in Melbourne by Geoff Lindeman, this clinical trial is looking at whether Denosumab prevents the development of the breast cancers that are caused by BRCA 1. We’re able to do that because Denosumab has been in routine use for around the last 10 to 15 years; we know the general side effects and we know that it’s a safe drug. “
Can you tell us a little more about the details of the trial?
“The BRCA P trial is a placebo-controlled, randomised trial (the gold standard trial for medication effectiveness when there is no standard treatment), and Denosumab is used at a relatively low dose, which reduces the risk of any side effects. Patients will sometimes feel a few mild aches, perhaps for 24 hours afterwards. And then that all goes away.”
Are there any risks that participants should be aware of?
“They may develop low levels of calcium in the blood, but that is minimised by taking calcium tablets and having enough calcium in their diet. However, participants who are undergoing dental work need to be fairly careful and a dentist needs to be aware of it, because Denosumab can slow the healing of the jaw. But, really, that’s something that can be prevented with adequate knowledge and education. Participants in this trial will receive treatment over five years, as an injection just under the skin, once every six months. This injection isn’t painful, and people tend to tolerate it very well.
How many participants do you need and how do people volunteer?
“Well, the trial began earlier in this year, but as it’s such a large trial, we need a lot of patients in order to show if there’s a difference between the drug and placebo. The trial needs to enrol just under 3000 patients with a BRCA 1 gene mutation. So, it’s very ambitious, but there are sites around Australia and internationally who are recruiting patients. You can find out more at the Breast Cancer Trials BRCA-P website.”
Who is eligible?
“We are looking for women aged between 25 and 55 with a BRCA1 gene mutation, who have not had breast cancer and have not had surgery to remove both of their breasts. But they can still participate if they have had their ovaries removed, because we know that these women are at risk of ovarian cancer.”
And lastly, why are you excited about this trial and what could it achieve?
“This trial will provide additional choices for at-risk women, who may have this constant worry about breast cancer in the future if they keep their breasts. Some women may still choose surgery, because they want to be absolutely certain of their risk, but this trial means that women with BRCA 1 gene mutation may be able to live more of a normal life with less fear of developing breast cancer in future. It could be a game-changer for women around the world.”
Thank you for visiting Pink Hope! Keep reading our blog for more articles about breast and ovarian cancer, and find out how to volunteer, support or donate to Pink Hope in the future. Pink Hope is a preventative health hub providing essential tools for assessing, managing and reducing your risk of breast and ovarian cancer, as well as providing personalised support for at-risk women.