Chances are, someone you know has been or will be affected by breast cancer.
But a recent discovery by a group of Montreal researchers into the genetic mechanisms at play in an aggressive form of the disease known as triple-negative breast cancer is fueling new hope for some of those being impacted by it.
Lebrun, who has been doing cancer research since he was appointed to McGill some 25 years ago, said the team focused on triple-negative breast cancer or “TNBC” to address what he described as a medical gap.
“There are some breast cancers that can be cured using drugs or surgery, but the triple-negative breast cancer … there’s no efficient, targeted therapies,” he said. “The only recourse we have are usually chemotherapy and radiotherapy.”
Existing drugs and therapies target specific proteins, such as estrogen receptors, progesterone receptors or human epidermal growth factor receptors (HER2), which are normally found in breast cancer cells.
For example, those with HER2-positive breast cancer will test positive for the HER-2 protein. Lebrun said a drug called Herceptin can be used to treat those cases.
“Itis an antibody that targets that receptor,” he explained, whereas “Tamoxifen — an anti-estrogen therapy — works well for women with hormone receptor-positive breast cancer.
TNBC doesn’t express any of those three proteins, meaning the cells test negative on all three tests, hence the “triple-negative” in the name.
And while TNBC isn’t as common — it makes up only 15 to 20 per cent of all breast cancers — Lebrun says it is by far the deadliest, accounting for half the deaths.
“Mortality rates are very high and the overall survival rates are very short. So people with this disease usually have months to live, not years,” he said.
Changing those outcomes is what motivated Lebrun’s team to take on TNBC.
Rather than using a hypothesis-driven approach which would have meant picking a protein and trying to target it, Lebrun said they opted for a systemic approach.
But that meant screening the entire human genome or roughly 20,000 genes.
“We want to know which ones out of those are actually important in the process of tumour formation in those TNBC,” he said.
To do that, scientists used gene-editing technology known as CRISPR, to cut each of the 20,000 genes one-by-one in a process referred to as “silencing” or “knocking out.”
And while it wasn’t quite like searching for a needle in a haystack, Lebrun said it was a painstaking process.
“When we started about five years ago, the technology was there, but just born,” he said of CRISPR. “So what sounds like much easier today to do was a lot more difficult at that time because we had to develop and optimize many of the tools ourselves.”
Following analysis, Lebrun said they were able to narrow down their search to around 350 genes, eventually identifying two signalling pathways or gene networks of significance.
“One of them was an oncogenic pathway. Those are genes that normally promote cell proliferation on tumours and this one was hyperactivated in those breast cancer patients,” Lebrun said.
The second group of genes, which normally act as tumour suppressors by preventing cells to multiply, were found to be inactive or asleep.
This combination, Lebrun believes, could explain why TNBC tumours are so “aggressive and metastatic.”
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Understanding which genetic mechanisms were involved allowed the team to then uncover existing drugs that targeted those networks.
One of the drugs they tested, Verteporfin, surprisingly had nothing to do with cancer.
“It’s actually a drug that is used for disease of the degeneration of the retina. It’s an eye disease,” Lebrun said.
“When we saw that this drug was able to target the genes that we were interested in, we said, ‘Let’s test that one out for the other network.’”
In all, the team evaluated around 10 different drugs, with Verteporfin being one of two standouts.
“When we tested each drug individually, they both worked,” Lebrun said. “So we were very happy because somehow it was validating our whole strategy, which was to identify the gene, find corresponding drugs and demonstrate that both drugs are working.”
Lebrun’s team was in for a pleasant surprise, however, finding that when combined, the drugs had a much bigger effect than anticipated.
Individually, each drug had around a 20 per cent decrease in tumour growth, so combined, Lebrun said they were expecting around 40 per cent inhibition.
“But we got something more like 80 per cent,” he said. “That’s what we call a synergistic effect.”
Lebrun and his RI-MUHC award-winning team.
Courtesy Jean-Jacques Lebrun
The team’s work hasn’t gone unnoticed.
It was recently awarded Québec Sciences magazine’s prestigious Discovery of the Year Award for 2021.
“It means a lot. … I’m super happy for the team,” Lebrun said. “It’s always nice to have your work recognized. … At least we can say, ‘OK, once I did something that contributed to the health of the population.’”
And while Lebrun is pleased with the accolades, he’s not one to rest on his laurels.
“I think that it’s a significant advancement in the field,” he said. “But you know, when I see it reflected in a clinical trial, then I will be happier.”
Efforts have been underway since the summer to get Phase 1 clinical trials off the ground, but Lebrun says there are many hurdles to overcome.
The first is that trials take time to set up. Lebrun said there’s a lot of administrative work and you also need ethical approval to go ahead.
Then there is the cost of the trial itself.
“It’s complicated because you need sponsors,” Lebrun said. “Even the Phase 1 clinical trial — you need several millions of dollars to start with.”
And that doesn’t include the cost of the drugs themselves, some of which, like Verteporfin, can be extremely expensive to produce, according to Lebrun.
“When you’re going to do that in humans, you need huge quantities of those drugs and that is something that sometimes we don’t think about,” he said, again pointing to the need for partnerships.
And while discussions are underway to that effect, Lebrun said he couldn’t give a timeline of when the trial would start and when patients could begin enrolling.
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.
