A drug originally designed to prevent osteoporosis is now expected to save and improve the lives of millions of people with breast cancer, thanks in part to decades of foundational research by Dr. Josef Penninger, a professor in UBC’s Faculty of Medicine and director of the Life Sciences Institute.
The achievement highlights how UBC scientists are developing effective new treatments — and unlocking the full potential of existing drugs – through research into the fundamental biological principles behind disease. By advancing scientific discoveries from the lab to the clinic, UBC researchers are bringing life-changing treatments to patients everywhere.
The drug, called Denosumab, was recently shown in a long-term Phase 3 clinical trial to improve survival among postmenopausal women with hormone receptor-positive early breast cancer receiving aromatase inhibitor treatment. Moreover, the drug markedly improved patients’ quality of life by reducing broken bones by 50 per cent, a common side effect of breast cancer treatment. The results of the trial were recently reported in The New England Journal of Medicine.
Denosumab is a monoclonal antibody developed by American biopharmaceutical company Amgen to prevent bone loss. In the early 2000s, research by Dr. Penninger and his team revealed the therapeutic potential of Denosumab, as well as the drug’s surprising connections with breast cancer.
“More than two decades ago we started the experimental groundwork that revealed Donosumab’s potential as a treatment for breast cancer patients,” says Dr. Penninger. “These results are incredibly exciting and will help improve the lives of millions of patients. I am very proud of all the people in my lab over the years who did that work and helped pave the way for this achievement.”
Discovering the link between osteoporosis and breast cancer
Denosumab works by binding to and inhibiting the activity of a protein called RANKL, which plays a key role in bone-resorbing cells called osteoclasts. By blocking RANKL, denosumab reduces the activity of osteoclasts and slows down bone resorption, helping to increase bone density and preventing osteoporosis.
Dr. Josef Penninger
Dr. Penninger and his team began to draw the connection between osteoporosis and HR-positive breast cancer when they generated the first RANKL “knock-out” mice in the late 1990s.
A knockout mouse is a laboratory mouse that has been genetically engineered to have certain genes deactivated, or “knocked-out”. Dr. Penninger’s team engineered mice that lacked the genes necessary to produce the RANKL protein in an effort to study the protein’s essential function in bone metabolism.
However, to the researchers’ surprise, they discovered that the RANKL-deficient mice failed to develop a lactating mammary gland in pregnancy – a process that depends on sex hormones.
“This proved an evolutionary link: showing how bone loss is regulated by sex hormones, and how pregnant mammals activate RANKL to form breast tissue for lactation among other functions,” says Dr. Penninger.
Based on this initial finding, Dr. Penninger’s team went on to show that RANKL played a key role in progestin-driven breast cancer, as well as breast cancer driven by BRCA1 mutations.
“Further researcher revealed how RANKL controls the stem cells in the breast that respond to sex hormones and thereby drives growth of the breast tissue at every menstruation cycle and in particular in pregnancy and lactation,” adds Dr. Penninger.
In the case of breast cancer, RANKL spurs mammary epithelial cells to divide, and helps to maintain the stem cells that give rise to breast tumours.
A dual benefit drug
One in eight Canadian women will be diagnosed with breast cancer in their lifetime according to the Canadian Breast Cancer Network. An estimated 70 to 80 per cent of these breast cancers are hormone receptor-positive (HR-positive), making it the most prevalent breast cancer subtype.
The current standard treatment for HR-positive breast cancer involves surgery and radiation, followed by treatment with aromatase inhibitors for 5 to 7 years. While aromatase inhibitors diminish sex hormones that drive new cancer growth, they can have serious adverse effects on bone health, including increased risk of osteoporosis and fractures.
The now-published clinical trial, led by the Austrian Breast and Colorectal Cancer Study Group, was conducted to see if Denosumab could help in two ways: by reducing these negative effects on bone health, while also improving breast cancer survival outcomes.
“These results are incredibly exciting and will help improve the lives of millions of patients.” Dr. Josef Penninger
The results reveal that 6 mg of Denosumab every six months — the recommended treatment level for osteoporosis — improved disease-free survival, bone metastasis-free survival, and overall survival among participants. It also effectively reduced bone fractures over the long term.
“Blocking RANKL in breast cancer patients reduces broken bones by 50 per cent, massively improving their quality of life, and even at a very low treatment dose,” says Dr. Penninger. “We now know that RANKL drives breast cancer cell growth, is the critical mechanism behind bone loss, and has also an effect on anti-cancer immunity and immunological rewiring in pregnancy. These clinical results in patients show how blocking RANKL could save the lives of 50,000 women among one million women with the diagnosis of breast cancer.”
Based on the data, the researchers behind the trials are recommending that Denosumab be considered for routine clinical use in postmenopausal breast cancer patients receiving aromatase inhibitor therapy.
These trials were largely based on the foundational research published by the Penninger laboratory, including Kong et al. Nature 1999, Fata et al. Cell 2000, Jones Nature 2006, Schramek et al. Nature 2010, Sigl et al. Cell Research 2016, and Paolino et al. Nature 2021.
Dr. Penninger is now part of a large international prevention trial evaluating Denosumab in young women who carry BRCA1 mutations.
The Canadian government says it will donate up to 200,000 vaccine doses to fight the mpox outbreak in Congo and other African countries.
It says the donated doses of Imvamune will come from Canada’s existing supply and will not affect the country’s preparedness for mpox cases in this country.
Minister of Health Mark Holland says the donation “will help to protect those in the most affected regions of Africa and will help prevent further spread of the virus.”
Dr. Madhukar Pai, Canada research chair in epidemiology and global health, says although the donation is welcome, it is a very small portion of the estimated 10 million vaccine doses needed to control the outbreak.
Vaccine donations from wealthier countries have only recently started arriving in Africa, almost a month after the World Health Organization declared the mpox outbreak a public health emergency of international concern.
A few days after the declaration in August, Global Affairs Canada announced a contribution of $1 million for mpox surveillance, diagnostic tools, research and community awareness in Africa.
On Thursday, the Africa Centres for Disease Control and Prevention said mpox is still on the rise and that testing rates are “insufficient” across the continent.
Jason Kindrachuk, Canada research chair in emerging viruses at the University of Manitoba, said donating vaccines, in addition to supporting surveillance and diagnostic tests, is “massively important.”
But Kindrachuk, who has worked on the ground in Congo during the epidemic, also said that the international response to the mpox outbreak is “better late than never (but) better never late.”
“It would have been fantastic for us globally to not be in this position by having provided doses a much, much longer time prior than when we are,” he said, noting that the outbreak of clade I mpox in Congo started in early 2023.
Clade II mpox, endemic in regions of West Africa, came to the world’s attention even earlier — in 2022 — as that strain of virus spread to other countries, including Canada.
Two doses are recommended for mpox vaccination, so the donation may only benefit 100,000 people, Pai said.
Pai questioned whether Canada is contributing enough, as the federal government hasn’t said what percentage of its mpox vaccine stockpile it is donating.
“Small donations are simply not going to help end this crisis. We need to show greater solidarity and support,” he said in an email.
“That is the biggest lesson from the COVID-19 pandemic — our collective safety is tied with that of other nations.”
This report by The Canadian Press was first published Sept. 13, 2024.
Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.
HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.
The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.
Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.
“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”
The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.
A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.
Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.
“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.
Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.
The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.
“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.
This report by The Canadian Press was first published Sept. 11, 2024.
ST. JOHN’S, N.L. – Newfoundland and Labrador‘s chief medical officer is monitoring the rise of whooping cough infections across the province as cases of the highly contagious disease continue to grow across Canada.
Dr. Janice Fitzgerald says that so far this year, the province has recorded 230 confirmed cases of the vaccine-preventable respiratory tract infection, also known as pertussis.
Late last month, Quebec reported more than 11,000 cases during the same time period, while Ontario counted 470 cases, well above the five-year average of 98. In Quebec, the majority of patients are between the ages of 10 and 14.
Meanwhile, New Brunswick has declared a whooping cough outbreak across the province. A total of 141 cases were reported by last month, exceeding the five-year average of 34.
The disease can lead to severe complications among vulnerable populations including infants, who are at the highest risk of suffering from complications like pneumonia and seizures. Symptoms may start with a runny nose, mild fever and cough, then progress to severe coughing accompanied by a distinctive “whooping” sound during inhalation.
“The public, especially pregnant people and those in close contact with infants, are encouraged to be aware of symptoms related to pertussis and to ensure vaccinations are up to date,” Newfoundland and Labrador’s Health Department said in a statement.
Whooping cough can be treated with antibiotics, but vaccination is the most effective way to control the spread of the disease. As a result, the province has expanded immunization efforts this school year. While booster doses are already offered in Grade 9, the vaccine is now being offered to Grade 8 students as well.
Public health officials say whooping cough is a cyclical disease that increases every two to five or six years.
Meanwhile, New Brunswick’s acting chief medical officer of health expects the current case count to get worse before tapering off.
A rise in whooping cough cases has also been reported in the United States and elsewhere. The Pan American Health Organization issued an alert in July encouraging countries to ramp up their surveillance and vaccination coverage.
This report by The Canadian Press was first published Sept. 10, 2024.
