Cancer Drug May Do Double Duty

An existing medication may hold the promise of preventing breast cancer in women who carry a faulty BRCA1 gene.

“We think this strategy could delay or prevent breast cancer in women with an inherited BRCA1 gene mutation,” said one researcher.

Denosumab is already used in the clinic to treat osteoporosis as well as breast cancer that has spread to the bone. Australian researchers say, however, that the drug may actually prevent an aggressive form of breast cancer in women at high risk for it.

The BRCA1 gene puts a person at high risk of developing an aggressive form of breast cancer. Currently many women with the mutation — Angelina Jolie, among the more recent high-profile cases — choose surgical removal of their breast tissue and ovaries to reduce their chance of developing breast and ovarian cancer.

“This is potentially a very important discovery for women who carry a faulty BRCA1 gene, [women] who have few other options. Current cancer prevention strategies for these women include surgical removal of the breasts and/or ovaries, which can have serious impacts on people’s lives,” said professor Geoff Lindeman, a medical oncologist at The Royal Melbourne Hospital.

Lindeman, along with Emma Nolan, and professor Jane Visvader, were able to pinpoint the cells that give rise to breast cancer by using samples of breast tissue donated by women carrying the BRCA1 gene. The research, which also involved work at the Australian familial cancer consortium kConFab and U.S. biotechnology company Amgen, was published Monday (June 20) in Nature Medicine.

Cancer precursor cells in BRCA1-mutant breast tissue have many similarities to aggressive forms of breast cancer, said Nolan, a Ph.D. student at the institute enrolled in The University of Melbourne’s Department of Medical Biology.

Related: Top 5 Foods Cancer Patients Should Eat

“These cells proliferated rapidly and were susceptible to damage to their DNA — both factors that help them transition toward cancer,” she said. “We were excited to discover that these pre-cancerous cells could be identified by a marker protein called RANK.”

Lindeman said the discovery of RANK for cancer precursors was an important breakthrough, because inhibitors of the RANK signaling pathway were already in clinical use — i.e., denosumab.

“We therefore investigated what effect RANK inhibition had on the cancer precursor cells in BRCA1-mutant breast tissue,” Lindeman added.

The research team showed that RANK inhibition switched off cell growth in breast tissue from women with a faulty BRCA1 gene and curtailed breast cancer development in lab models.

“We think this strategy could delay or prevent breast cancer in women with an inherited BRCA1 gene mutation,” Lindeman said. “A clinical trial has already begun to investigate this further.”

[lz_ndn video=31001018]

Denosumab would need to be formally tested in clinical trials in this setting, since it is not currently approved for breast cancer prevention, Lindeman added.

Visvader said the discovery had its basis in more than a decade of investigations of breast stem cell function.

“By thoroughly dissecting how normal breast tissue develops, we have been able to pinpoint the precise cells that are the culprits in cancer formation,” she said. “It is very exciting to think we may be on the path to the ‘holy grail’ of cancer research, devising a way to prevent this type of breast cancer in women at high genetic risk.”

The research was supported by a number of organizations, including the National Breast Cancer Foundation, the Australian Cancer Research Foundation, the Victorian Government Operational Infrastructure Support Scheme and many others.