A trial in mice has shown that the drug denosumab could become a preventative breast cancer treatment for women with BRCA1 gene mutations

Women who have a high risk of breast cancer may benefit from a drug that is already prescribed to treat bone loss in old age, according to scientists in Australia.



Researchers found that the osteoporosis drug, denosumab, can halt the growth of cells which give rise to breast tumours in women whose risk of the disease is greater because of mutations in a gene called BRCA1.



Though promising, the work is at an early stage and the results gleaned so far from lab tests on mice and breast tissue must be reproduced in large human trials before the drug can be considered as a preventative treatment.



Healthy BRCA1 and BRCA2 genes help the body repair damaged DNA. But when either gene is mutated, the risk of breast and ovarian cancers can rise steeply. About half of women who inherit a harmful mutation in BRCA1 or BRCA2 will develop breast cancer by the age of 70.



Women who discover they carry harmful BRCA mutations can opt for preventative surgery to remove their breasts, or have more intensive screening for tumours. “We were interested in finding an alternation option, a non-surgical approach for these women,” said Emma Nolan at the Walter and Eliza Hall Institute of Medical Research in Victoria.



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The scientists analysed breast tissue donated from a woman diagnosed with BRCA1 mutations. From this, they isolated a distinct group of cells that grew rapidly and appeared to be precursors of breast tumours.



Further examination of the cells revealed that they carried a protein marker on the surface, called RANK1. The same protein is targeted by denosumab, which is already used to treat osteoporosis and breast cancer which has spread to the bone.



In lab tests reported in the journal Nature Medicine, denosumab blocked the growth of the cancer precursor cells and slowed the growth of tumours in mice bred to develop breast cancer.



“We are very excited by these findings because it means we’ve found a strategy that might be useful to prevent breast cancer in very high risk women, particularly BRCA1 mutation carriers,” said Geoff Lindeman, a medical oncologist at the Royal Melbourne Hospital. He said a clinical trial to assess the drug in patients has already started.



Emma Smith at Cancer Research UK said: “Insights into the molecules causing tumour growth in women with faulty BRCA1 genes could lead to new treatments reducing the risk of developing breast cancer, giving these women another option to lower their risk. But this study was carried out in mice and on cells in the lab, so we don’t know how effective this approach could be at reducing breast cancer risk in women, or how it compares with options for prevention that are already available.”