Investigating prevention strategies for altered BRCA1-related breast cancers

People who inherit an altered BRCA1 gene from either parent have a much higher risk of developing breast cancer. Altered BRCA1-related breast cancers more frequently lack the oestrogen receptor, and so are oestrogen receptor negative (ER-). While women at high risk of oestrogen receptor positive (ER+) breast cancers can be offered hormone therapy, such as tamoxifen, to prevent breast cancer, these treatments often don’t work for women with an altered BRCA1 gene. This means that the only way to prevent breast cancer from developing for these women is bilateral mastectomy. Therefore, we urgently need to find other effective ways to prevent altered BRCA1-related breast cancers.

The drug denosumab is currently used to strengthen the bones of people with osteoporosis, and to help prevent fractures and other bone problems in people whose cancer has spread to the bone. New research suggests that it could also prevent a type of healthy breast cell from turning into cancer in women with an altered BRCA1 gene.

In this project, Dr Sacha Howell and his team will take breast biopsies from women taking part in the BRCA-P clinical trial, who have a change in BRCA1 gene and haven’t had a diagnosis of breast cancer. This international clinical trial is investigating whether denosumab is a safe and effective way of preventing breast cancer in women with altered BRCA1 genes.

Sacha and his team will study biopsies taken before and after a four-week course of denosumab, and analyse these to work out how denosumab might reduce the chances of breast cancer developing. In a previous study funded by Breast Cancer Now, Sacha and his team found that blocking the function of a molecule called the progesterone receptor may be a way to prevent breast cancer in women at high risk of the disease who do not have BRCA1 gene changes. By comparing the results of these two studies, researchers hope to find a more promising way to prevent ER-negative breast cancer that could be studied further.

Hormone therapies can be used to prevent some ER+ breast cancers, but we currently lack preventive options for women at high risk of ER- breast cancer. Sacha and his team are trying to understand the potential of a new treatment that could prevent ER- breast cancer. If successful, this project could lead to new ways to prevent ER- breast cancers, and could also reduce the need for preventive mastectomies. Overall, this research has the potential to spare many from the anxiety and stress of a breast cancer diagnosis, or surgery to remove healthy breasts.