A Canadian-led study is challenging a long-standing assumption in cancer care: that more treatment is always better.
Researchers say their findings could change how an estimated two million women with early-stage breast cancer are treated each year, around the world and in Canada.
“The results have been an absolute slam dunk, affecting the care of around 30,000 Canadian patients a year and two million patients globally every year,” said Dr. Mark Clemons, an oncologist at the Ottawa Hospital, and a member of the study team.
The study, published in the Journal NEMJ Evidence, was conducted at several hospitals in Ontario. It didn’t test a new drug or a more intensive or powerful treatment regimen. Instead, it tested something far simpler: whether patients could safely receive far less treatment with a similar long-term effect.
The answer, researchers say, appears to be yes. And one of the test subjects, Beth Ciavaglia, of Ottawa, applauds the results.
“If we’re needing less intervention to have as good an outcome, it’s a win-win scenario from every angle,” Ciavaglia told CTV News.
The trial studied the use of zoledronic acid – a drug often given to women with early-stage breast cancer. Studies from more than a decade ago found it reduced the risk of the cancer spreading to the bones. Current guidelines typically recommend the medication be given intravenously, every six months for three years for a total of seven infusions.
But Canadian researchers asked a provocative question: what if only one dose was enough?
The study followed 211 women with early-stage breast cancer and who were post-menopause. Half received the recommended seven doses of zoledronic acid, compared to women who received a single infusion.
In the study, scientists report that when they followed up with both groups of women after five years, they found no meaningful difference in cancer recurrence, cancer spread or death. At the same time, patients who received just one treatment experienced fewer side effects, fewer hospital visits, and less disruption to their lives.
“Patients no longer need to come back to the cancer centre every six months for three years,” Clemons, who led the study, said. “A single infusion means less toxicity, less blood tests, and more time with your family and loved ones,” he added.
Researchers have long known that zoledronic acid remains in bone tissue for a long time, giving scientists a reason for launching this research.
“We knew a single infusion would stay in the body for 10 years, so it made no sense giving the drug every six months,” said Clemons.
The challenge was convincing patients to participate in a trial that deliberately reduced treatment. It runs counter to prevailing wisdom in the field of cancer therapy that more aggressive treatments are better.
Ciavaglia admits she initially feared the less aggressive therapy.
“At first, I said ‘no’ to the trial,” she recalled. “I had that same instinct I think most breast cancer patients do, that it felt too risky. I didn’t want to take less.”
Ciavaglia had already endured surgery, six rounds of chemotherapy, and more than two dozen radiation treatments when she was offered the opportunity to join the study. After discussions with her oncologist, she agreed.
“I was sorted into the one-time intervention group, and I still remember feeling nervous,” she said.
The single dose was not easy.
“The side effects were terrible,” Ciavaglia said, describing the experience as something like a severe flu.
“The scariest part was in the middle of the night… I started to get these full-body shakes. I remember thinking, ‘What is happening to me?’” she said.
Those symptoms eventually passed, but the experience reinforced the potential value of avoiding repeated treatments.
“I actually remember saying to myself, ‘I’m so glad I don’t have to do that six more times,’” Ciavaglia said.
She says receiving only one infusion allowed her to return more quickly to her family and career as executive director of Ottawa’s Parkdale Food Centre.
“It meant more quality time with my kids,” she said. “It meant less of that treatment dread. You look at your calendar and think, ‘that’s coming next month.’ I didn’t have to worry about that anymore.”
Seven years later, Ciavaglia remains cancer-free.
Zoledronic acid belongs to a class of medications known as bisphosphonates. The drug is used to strengthen bones and to cut the risk of cancer spread in post-menopausal women with breast cancer. Previous studies established the drug’s benefits, leading to recommendations patients receive seven doses over three years.
However, each infusion comes with a heavy burden, because patients require blood work before each dose and must repeatedly travel to cancer clinics. Side effects can include fever, nausea, flu-like symptoms, kidney complications, and, in rare cases, serious bone loss in the jaw.
“What this study showed was the side effects were much reduced with the single infusion, and patients were able to get on with their lives sooner,” said Clemons.
The ‘de-escalation’ movement
The findings are part of a growing movement within oncology known as "de-escalation." Rather than asking whether more treatment can improve outcomes, researchers are increasingly asking whether less treatment can achieve the same results, while reducing toxicity and sparing patients the repeated bouts of fatigue and other side effects after repeated treatments.
Dr. Bishal Gyawali, a medical oncologist and associate professor at Queen’s University in Kingston, says the shift reflects a broader change in cancer care philosophy.
“The whole field of oncology is usually focused on what we can do more for our patients,” Gyawali said. “Can we give more drugs? Can we give higher doses? Can we give it more frequently?”
For decades, cancer treatment was guided by a belief that maximum treatment would produce maximum benefit.
“That is flawed thinking,” Gyawali said, who was not involved in this study.
“The goal is not just to shrink the tumour or melt away the tumour. The goal is to live as long a life as possible with a good quality of life,” he said.
He notes that some cancer interventions may extend survival by only a small amount at significant personal cost.
“Those couple of months could be very miserable months — in the ICU, in the emergency department, in the hospital, not being able to spend time with loved ones, " said Gyawali. “We have now come to a realization that we are probably over-treating patients.”
The zoledronic acid trial fits squarely within that trend, with the cancer specialist convinced the results tell an important story that patients should discuss with their oncologists.
“Based on the cumulative evidence, this study is enough to convince me that a single dose should be enough for most of our patients who meet the criteria for this trial,” Gyawali said. “I’d be totally confident with recommending my patients just a single dose.”
Gyawali is part of an international group of scientists, who established “Common Sense Oncology,” an association that is promoting more investigation of better dosing for patients and their quality of life.
However, in an editorial in the same journal, Harvard scientist, Dr. Neelima Vidula, who reviewed the study, said she is cautious.
“My take is that it is not ready for the universal de-escalation in all patients with breast cancer for the reasons cited in the paper,” she told CTV News in an email.
Vidula points out that the women who received the single dose had a slightly higher risk of osteoporosis and bone fracture, compared to women who toughed it out and had all seven doses.
But the Harvard scientist also suggested that patients who were at a lower risk for the cancer to move into their bones, had experienced bothersome side-effects from the medication. They could discuss “whether to stop after one dose” with their doctors, she added.
Guidelines for care have not been changed yet as a result of the study. While the results are not part of any official guidelines, they are on the radar for cancer agencies.
“Clinical trials like this provides important real-world evidence that clinicians can apply in their care of patients,” officials from Ontario Health (Cancer Care Ontario) wrote in a statement for CTV News. “We are aware of this research and it is under discussion,” the statement added.
Still, the broader de-escalation movement has been gaining momentum across cancer care. Researchers are studying shorter courses of radiation therapy, lower doses of medications, less extensive surgery, and more personalized treatment strategies. The goal is not to compromise outcomes, but to optimize treatment — maintaining effectiveness while reducing harm.
The Canadian study also stands out because it was not funded by the pharmaceutical industry, rather supported by charitable funding from groups like the CURE Foundation, the Ottawa Hospital Research Institute, and the Ottawa Hospital Foundation.
Ciavaglia, meanwhile, was not only able to return to work faster than expected, but she also talks to other patients navigating breast cancer. She is also seven years cancer-free.
“I remain hopeful and will advocate as much as I can to make sure this information gets out,” said Ciavaglia.
“The brave patients who took part in this study may have had concerns that they were receiving less treatment,” said Clemons. “But what we keep finding in medicine is that more isn’t better. More is associated with no additional benefits, but with a lot of toxicity and a lot of cost to patients and their families.”
