New data will add fuel to the ongoing debate over the age at which mammography screening for breast cancer should begin. Many guidelines recommend starting at age 50.
But yearly mammography between the ages of 40 and 49 years was associated with a "substantial and significant" 25% reduction in breast cancer mortality during the first 10 years of follow-up, according to new data from the UK Age Trial.
The researchers calculated that 1150 women needed to undergo screening in the age group of 40-49 years to prevent one breast cancer death, or about one breast cancer death prevented per 1000 screened.
However, they also note that in the years since the trial first began there have been improvements in the treatment of breast cancer, so "there might be less scope for screening to reduce mortality in our current era."
The study was published online August 12 in Lancet Oncology.
"Our results do indicate that screening before age 50 does indeed prevent deaths from breast cancer, with a minimal additional burden of overdiagnosis," said lead author Stephen W. Duffy, MSc, director of the Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis, at Queen Mary University, London, UK.
That said, Duffy explained they do not expect policymakers to extend the age range on the basis of these results alone. "For one thing, they will want to consider costs, both human and financial," he told Medscape Medical News. "For another, at this time, the services are concentrating on recovering from the hiatus caused by the COVID-19 crisis, and at this time, it would be impractical to try to expand the eligibility for screening."
"I would say our results indicate that lowering the age range, although not necessarily to 40 but to some age below 50, will be at least worth considering when the current crisis is over," he added.
Guideline Recommendations Differ
Breast cancer screening guidelines have generated debate, much of which has focused on the age at which to begin screening.
The US Preventive Services Task Force (USPSTF) and American College of Physicians recommend screening every other year for women on average between the ages of 50 and 74 years.
However, other organizations disagree. The American College of Radiology and Society of Breast Imaging both recommend annual mammograms starting at age 40, and continuing "as long as they are in good health."
In the UK, where the study was conducted, a national breast cancer screening program offers mammography to women aged 50-70 years every 3 years.
Given the uncertainty that continues to exist over the optimal age for average-risk women to begin screening, the UK Age Trial set out to assess if screening should begin at a younger age and if that might lead to overdiagnosis of breast cancer.
Results from the study's 17-year follow-up, published in 2015, showed a reduction in breast cancer mortality with annual screening, beginning at age 40 years, which was significant in the first 10 years after participants were randomized (Lancet Oncol. 2015;16:1123-32).
In the current study, Duffy and colleagues report on breast cancer incidence and mortality results in the UK Age trial after 23 years of follow-up.
The cohort included 160,921 women enrolled between October 14, 1990, and September 24, 1997, who were randomized to screening (n=53,883) or the control group (n=106,953).
Of those screened during the study period, 7893 (18.1%) had at least one false-positive result. There were 10,439 deaths, of which 683 (7%) were attributed to breast cancer diagnosed during the study period.
At 10 years of follow-up, death from breast cancer was significantly lower among women in the screening versus control group (83 vs 219 deaths; RR, 0.75; P = .029).
However, no significant reduction was observed thereafter, with 126 versus 255 deaths occurring after more than 10 years of follow-up (RR, 0.98; 95% CI, 0.79 - 1.22; P = .86), the authors note.
"This follow-up indicates that the gain in survival was concentrated in the first 10 years after the women began to be screened," commented Kevin McConway, PhD, emeritus professor of applied statistics at The Open University, UK.
"In those first 10 years, out of every 10,000 women invited for screening, on average about 16 died of breast cancer, while in every 10,000 women in the control group who did not get the screening, on average 21 died. These numbers indicate that lives were saved," he said.
"But they also indicate that death from breast cancer was pretty rare in women of that age," he pointed out.
"Because breast cancer deaths in younger women are not common, the estimates of breast cancer death rates are not very precise, despite the fact that the trial involved 160,000 women," he said.
"Over the whole follow-up period so far, the difference in numbers of deaths between those who were screened in their 40s and those who were not is six deaths for every 10,000 women, but because of the statistical uncertainty, this figure could plausibly be larger, at 13 per 10,000. Or, in fact, the data are also consistent with a very slightly higher death rate (1 death per 10,000 women) in those who had the screening," McConway explained.
"But none of those numbers is very large, out of 10,000 women. Allowing for the fact that not every woman invited for screening will actually attend the screening, the researchers estimate that 1150 women would have to be screened in their 40s to prevent one breast cancer death," he noted.
US Experts Support Starting Screening at 40
Medscape Medical News approached two US breast cancer experts for their reaction to the new data from the UK.
"The American Society of Breast Surgeons has continued to recommend screening women at the age of 40," said Stephanie Bernik, MD, FACS, chief of breast surgery, Mount Sinai West, and associate professor of surgery at the Icahn School of Medicine at Mount Sinai, New York City. "There is no question that screening earlier saves more lives and this study adds to the body of evidence already available."
She pointed out that the argument against early screening was that there were many false positives, which in turn increased cost and anxiety. "Because women in their 40s are in the prime of their lives, often with young children, it seems as though screening would be paramount," said Bernik. "Furthermore, it is well known that the sooner you find a cancer, the better, as the treatment needed to cure the cancer is less toxic and less dramatic."
Catherine Tuite, MD, section chief, Breast Radiology, Fox Chase Cancer Center, Philadelphia, Pennsylvania, echoed a similar viewpoint. "There is no real debate on this issue," she said. "The USPSTF recommends beginning screening mammography at age 50, and it is no secret that this is a recommendation based on cost, not on saving women's lives."
She emphasized that these recommendations were made without the input of expert physicians. "The data, reaffirmed by this publication, have always been clear that the most years of life saved from deaths due to breast cancer are achieved in women who begin screening mammography at age 40," Tuite said. "We know that one sixth of all breast cancers are diagnosed before age 50, and many of these cancers are the most aggressive types of breast cancer."
"The guidelines from every organization representing health care professionals who actually diagnose and care for women with breast cancer recommend that all women of average risk begin annual screening mammography at age 40 and continue as long as the woman is in good health, with life expectancy of 10 years," she continued.
As for screening intervals, annual mammogram is also recommended for all age groups in the United States. At her institutions, she explained that they are currently enrolling women into the TMIST screening mammogram trial, which is, among other endpoints, evaluating a biannual screening interval for postmenopausal women of lower than average risk, but again, outside of a trial setting, yearly screening for all women is recommended.
Duffy commented that, in the UK, the current screening protocol for mammograms is every 3 years, which he says, "works well in women over the age of 50 years." But for younger women, more frequent screening would be need — in this study, screening was done annually.
"The results not only from our study but from others around the world suggest that this [3-year screening interval] would not be very effective in women under 50, due partly to the denser breast tissue of younger women and partly to the faster progression on average of cancers diagnosed in younger women," he said. "Some counties in Sweden, for example, offer screening to women under 50 at 18-month intervals, which seems more realistic."
The study was funded by the Health Technology Assessment program of the National Institute for Health Research (NIHR). Duffy has reported also receiving grants from the NIHR outside this trial. Bernik, Tuite, and Hodgson have reported no relevant financial relationships.
Lancet Onc. Published online August 12, 2020. Full text
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