New report on contentious breast cancer screening study divides researchers

TORONTO -

A new paper has called into question the scientific process behind the Canadian National Breast Cancer Screening Study (CNBSS) from the 1980s, a contentious study that has divided researchers for years.

Researchers from Toronto's Sunnybrook Research Institute, the Ottawa Hospital, the University of British Columbia, the University of Alberta and Harvard Medical School published their examination of the CNBSS in the Journal of Medical Screening this week, alleging that the original study had significant flaws, particularly in the randomization aspect of the research.

The CNBSS was a series of trials done in the 1980s at 15 screening centres in six provinces: Nova Scotia, Quebec, Ontario, Manitoba, Alberta and British Columbia. Close to 90,000 women aged 40 to 59 participated in the study.

Its purpose was to determine whether cancer screening programs helped saved women’s lives, and assigned the participants into two groups – one with women aged 40 to 49 and 50 to 59 that received mammograms and another control group where both age sets had a single physical exam.

All participants were followed by the study for several years.

Over the five year screening period, the CNBSS found that 666 invasive breast cancers were diagnosed in the group that received a mammogram and 524 were diagnosed in the control group that received a physical exam. Of those diagnosed, 180 women in the mammography group and 171 women in the control group died of breast cancer during the 25-year follow up period.

The overall risk ratio for death from breast cancer diagnosed during the screening period and the cumulative mortality from breast cancer was similar between the women in the group that received mammograms and those in the control group, the CNBSS found.

Researchers then determined from that data that mammograms for women aged 40 to 49 did not reduce death rates from breast cancer for women at average risk of the disease.

The CNBSS findings have influenced healthcare policy and guidelines on when women should be able to participate in screening programs, with the Canadian Task Force on Preventative Health Care (CTFPHC) guidelines currently not recommending breast cancer screenings with mammograms for women aged 40 to 49 if they do not have any pre-existing factors, such as a direct family member that had breast cancer or the BRCA gene.

In an emailed statement to CTVNews.ca Tuesday, CTFPHC co-chair Dr. Brenda Wilson said the organization “conducts rigorous, detailed evidence reviews to formulate guidelines. Our guidelines, including those on breast cancer screening, have been recognized as the best in the world…One reason for this is the careful and detailed process that the Task Force uses to weigh evidence, which is available in its guideline documentation.”

When asked if the CTFPHC would revisit said guidelines in light of the new paper’s allegations, the statement said “the Task Force integrates the best available evidence into its guidelines. When there are substantive changes to that evidence, the Task Force updates a full review of the body of evidence, including any new evidence. We do not comment on individual studies or opinion pieces without going through that process.”

RESEARCHERS DIVIDED

One of the co-authors of the new paper, radiologist Dr. Jean Seely, who is head of breast imaging at The Ottawa Hospital, told CTVNews.ca in a telephone interview Tuesday that experts around the world had “long suspected” that there were issues with the science of the CNBSS.

“They [the CNBSS] were the only randomized controlled studies out of eight to show no benefit from screening mammography,” she said. “A lot of questions were raised over the years [which] showed that there probably had been a problem with the randomization process, that allowed for more women with clinically advanced cancers to be allocated to the screening arm of the study.”

Seely says those suspicions are what pushed her and her fellow researchers to examine the CNBSS more closely, and in the process of their investigation determined that the trial participants had a clinical breast exam prior to being assigned to one of the two trial groups.

The new paper suggests that the breast examination influenced whether the women were put in the control group or the group which received mammogram screenings.

“We have very credible eyewitness testimony showing that that happened at two different sites,” Seely said. “On the ground evidence is that – with the best of intentions -- the nurses who had examined the women were allocating them to the mammography arm with the intention of getting them attention.”

Lead study author Dr. Martin Yaffe of the Sunnybrook Research Institute echoed Seely’s concerns.

“Our research reveals a number of protocol violations within the CNBSS related to how patients were randomized into the trial groups – to receive breast screening or not,” Yaffe said in a release. “Given these significant issues, the trial results are unreliable and should not be used to inform policies on breast cancer screening.”

The authors of the paper argue that the CNBSS should not be informing screening guidelines due to the “corruption of the randomization process,” according to Seely.

“We now know that many women who had symptomatic breast cancers were actually recruited…so it really should not inform screening guidelines today,” Seely said, adding that mammogram photo quality was poor during the trials time period.

Seely says she was “astonished” that the alleged data corruption could have occurred and the study was still published.

“It’s disturbing to me as well that we have conclusive evidence that this happened…I think as a Canadian myself, I felt a bit embarrassed or ashamed,” she said. “I think the bottom line is that women should not be hurt by this and they should be empowered to have good health and get screening.”

However, Dr. Cornelia Baines, professor emerita at the Dalla Lana School of Public Health at the University of Toronto, who worked on the CNBSS, categorically denied the new papers evidence in an email and telephone conversation with CTVNews.ca.

“Speculation and anonymous remarks do not constitute evidence,” Baines wrote in an email.

The JMS paper does, however, reference “eyewitness testimony” from named individuals, including employees and doctors at certain mammography sites

“The JMS article suggests women age 40-49 were seeking screening mammograms in the CNBSS because of symptoms," Baines said. "In fact women’s access to diagnostic mammograms regardless of age was available in our universal health care system. Unlike the U.S., Canadian women do not need to seek free care in research trials.”

“Nurse examiners did not need to thwart randomization protocol because of a positive clinical exam,” she continued. “A positive exam required a referral to the study’s surgeon, who was totally free to order a diagnostic mammogram.”

Baines says that the screening centre co-ordinators were independent of the examiners, and that there were only four criteria for entry into CNBSS: a woman’s age, that the women were not pregnant, there was no history of breast cancer and they had not had a mammogram in 12 months prior to the study.

“We expected women to be honest and virtually all were,” she wrote. “In 2019, the BMJ rated our 2014 paper on the CNBSS 25 year results as one of the five best it had published in the decade.”

“I will briefly tell you – it is radiologists who do not like our study [and] have been pushing this for three decades, you have to wonder why after 30 years of such attacks the CNBSS is still highly regarded by people other than radiologists,” Baines said in a telephone conversation with CTVNews.ca

THE HUMAN COST

Currently, there is no universal breast cancer screening program across the country. A woman in her 40s in B.C. can get screened for breast cancer, as can a woman of the same age group in Nova Scotia. In Ontario however, a woman needs a referral from their family doctor.

The authors of the new paper argue that screening should be available to any woman in her 40s to catch possible disease quicker.

For law professor Jennifer Quaid, early screening is something she often thinks about after her experience with breast cancer.

“I got excellent care and treatment…but what makes me angry is that it was preventable. I think it should have been picked up earlier,” the University of Ottawa professor said in a telephone interview with CTVNews.ca Tuesday.

Quaid, who is now in her 50s, found a small lump in November 2019 but put off seeing her doctor due to career demands and the subsequent COVID-19 pandemic where in-person visits to the doctor’s office were often delayed or discouraged. In the summer of 2020, she saw her doctor who requisitioned a mammogram for her.

“The tech came back in and said ‘the radiologist wants to have a quick chat with you,’ at which point I knew something was wrong,” Quaid said. She ended up being diagnosed with stage three breast cancer that required a full mastectomy and a full lymph node reduction.

“I'd just come off a very successful sabbatical where I had gotten every grant I had applied for and written some pretty significant papers,” Quaid said. “So I felt like I was ready to launch and all of a sudden it's like somebody just pulled the floor out from under you. That was probably the worst moment.”

Quaid had surgery, and went through chemotherapy, then radiation until mid-March 2021.

“I don't want to seem like I'm laying blame,” she said. “You know, people do the best they can. But my GP knew that …I have breast cancer in my family, but not my mother, and I don't have any sisters and my grandmothers did not have breast cancer. So under the Ontario rules I didn’t qualify [for screening].”

Quaid wants breast cancer screening to be offered to women earlier, as analysis on the tumours removed from her body during surgery revealed they had been there for at least one to two years.

“I will never be able to go back to exactly how I was before,” she said. “I also lost a year of productive work at the height of my career and those things I will never get back. So if I can prevent one other person from going through that, it's worth it.”