Breast cancer is on the forefront of many cancer research efforts, as it ranks as the most common cancer diagnosed in women younger than 40 years old in the US. And this massive research effort may be paying off, as researchers have announced the finding of a potent target
that already has an available drug. The finding has already led to a clinical trial, which the team hopes will bear fruit for cancer prevention in high-risk patients.
This year, an estimated 246,660 women in the US will be diagnosed with breast cancer. Mutations in the BRCA1 and BRCA2 genes, which are involved in DNA repair, can significantly increase an individual’s risk for breast and ovarian cancer, as well as recurrent cancers or later cancer in the opposite breast. Current cancer prevention strategies for patients can be grim and drastic, involving the surgical removal of the breasts and/or ovaries.
To pinpoint the cells that develop into breast cancers, the research team at the Walter and Eliza Hall Institute in Australia looked at breast tissues from women who have been diagnosed with BRCA1 mutations. They identified a subset of precursor cells that gave rise to full-blown breast cancer.
"These cells proliferated rapidly, and were susceptible to damage to their DNA -- both factors that help them transition towards cancer," said Emma Nolan, first study author. Furthermore, these cells had a traceable hallmark. "We were excited to discover that these pre-cancerous cells could be identified by a marker protein called RANK,” Nolan explained.
Putting the puzzle pieces together, the team realized that RANK could be easily inhibited with chemical agents already in clinical use. "An inhibitor called denosumab is already used in the clinic to treat osteoporosis and breast cancer that has spread to the bone," said Geoff Lindeman, medical oncologist at the Royal Melbourne Hospital, and senior study author. "We therefore investigated what effect RANK inhibition had on the cancer precursor cells in BRCA1-mutant breast tissue."
Indeed, they showed that denosumab stopped BRCA1-mutated cells from developing into breast cancer cells. "We think this strategy could delay or prevent breast cancer in women with an inherited BRCA1 gene mutation," Professor Lindeman said. "A clinical trial has already begun to investigate this further."
Remarking on the discovery, Lindeman said, “This is potentially a very important discovery for women who carry a faulty BRCA1 gene, who have few other options. To progress this work, denosumab would need to be formally tested in clinical trials in this setting as it is not approved for breast cancer prevention.”
"By thoroughly dissecting how normal breast tissue develops, we have been able to pinpoint the precise cells that are the culprits in cancer formation," said Jane Visvader, co-author of the study. "It is very exciting to think that 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."
Additional source: Walter and Eliza Hall Institute