A long-awaited study shows that screening for breast cancer with annual mammograms may not always be the best way to catch the disease.
In a study published in JAMA and presented at the San Antonio Breast Cancer Symposium, Dr. Laura Esserman, a breast-cancer surgeon and director of the University of California San Francisco Breast Care center, showed that more personalized screening schedules based on a woman’s risk of developing the disease could be just as effective at detecting cancer.
Esserman launched the WISDOM (Women Informed to Screen Depending on Measures of Risk) study in 2016 to explore whether more personalized evaluations of a woman’s risk of developing breast cancer could lead to alternative screening schedules that would serve them better than uniform yearly mammograms. The first results, which involved more than 28,000 women between ages 40 and 74, suggests that different screening regimens for women at higher and lower risk are as good as the existing annual screens.
The women, none of whom had breast cancer, were randomly assigned to receive either more personalized risk-based screening or the annual screening. They were followed for an average of about five years to see if they developed the disease. In this first analysis, Esserman and her team found that alternative screening regimens, including more-frequent or less-frequent screening, were similar to yearly screening in detecting breast cancer. That suggests cancers weren’t being missed with the alternative screening schedules.
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The number of Stage 2B breast cancers—the stage at which deaths from breast cancer rise sharply, from three- to eight-fold—was lower in the group with personalized screening compared to those getting yearly screening. “There was a one third reduction in the number of Stage 2B cancers; that’s remarkable,” says Esserman. “Even I am amazed by these results.”
WISDOM also showed that altering the screening schedule was not harming women by missing cancers. “This study is absolutely a prerequisite to implementation of a risk-based approach,” says Esserman. “The first thing we had to do was to show it is safe.”
Esserman has long been bothered by the uniform screening guidelines for breast cancer. She and other experts have long known that women have widely varying disease risk, and as researchers have learned more about genetic risk factors, for example, they have found several mutations that seem to be associated with higher risk. Studies also show that not all women who develop breast cancer have a family history of it, which has traditionally been one of the risk factors that doctors consider.
WISDOM’s risk-based strategy included genetic testing looking at nine breast cancer genes. On their own, some don’t have an appreciable effect on breast-cancer risk, but together research links them to higher risk. Other factors, like breast density, age, and a woman’s own history of the disease, as well as her family’s, were also included. Based on these risks, Esserman’s team developed an algorithm for assigning women to one of four different screening regimens. All women received counseling about risk factors, and women at highest risk got alternating mammograms and MRIs every six months. Women at elevated risk got annual mammograms; women at average risk were assigned to mammograms every other year, and those at lowest risk did not receive mammograms unless their risk score changed.
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The more personalized risk-based assessment provides more targeted screening that could benefit women, says Esserman. While the current study was just designed to show its safety, she plans to track treatments and outcomes. “We’re working on improving our risk-reducing tools and predicting risk so we can improve our efforts in prevention [of breast cancer],” she says. Current screening methods are too broad and don’t distinguish between high- and low-risk women, which leads to over-treatment of some and missing cancers in others. “We want to be finding people who have the highest risk of cancer,” she says.
Key to using risk-based screening is a robust algorithm that incorporates the latest understanding on major risk factors for the disease, and that means revising long-held views. The findings also make a strong case for routine genetic testing of women, beginning at relatively early ages, says Esserman, since many highest risk breast cancers begin when women are in their 30s or so. In the study, for example, 30% of women with high-risk genes did not have a family history of breast cancer. “That surprised everybody including us. It goes to show that family history is not a reliable way to determine who should have a genetic test,” says Esserman.
The study also showed that women’s expectations and preferences for breast-cancer screening are evolving. WISDOM was conducted during the pandemic, which changed people’s thresholds for screening. “People thought, ‘it would be good to know my risk to figure out whether I should go in [for the screening] or not,’ and I think that helped us,” says Esserman. “People were more reluctant to consider less screening until COVID happened.”
The WISDOM results support other studies in breast cancer that are exploring whether aggressive treatments for very early, low-grade cancers like DCIS are necessary. Earlier this year, the COMET study, led by Dr. Shelley Hwang at Duke University, showed that for some women diagnosed with DCIS, careful monitoring with more frequent mammograms did not lead to any higher risk of developing breast cancer than those who chose to do surgery and radiation to remove the lesions.
The current findings are just the start for WISDOM, which has already enrolled women for the next stage focusing on whether personalized risk-based screening can help to prevent cancer. “I would love to see this country adopt a comprehensive risk-based screening program,” says Esserman, noting that several countries in Europe, including the U.K., France, and the Netherlands, already rely on differing versions of this approach. “It’s pretty thrilling to have these results. More screening isn’t better; smarter screening is.”
