A long-awaited study suggests that breast cancer screening with an annual mammogram may not always be the best way to detect the disease.
In the study published in PIT and presented at the San Antonio Breast Cancer Symposium, Dr. Laura Esserman, a breast cancer surgeon and director of the Breast Care Center at the University of California, San Francisco, showed that more personalized screening schedules based on a woman's risk of developing the disease can be just as effective in detecting cancer.
Esserman launched WISDOM Study (Women Informed about Screening Based on Risk) in 2016 to explore whether more personalized assessment of women's breast cancer risk could lead to alternative screening schedules that would be more beneficial than uniform annual mammograms. The early results, which included more than 28,000 women aged 40 to 74 years, suggest that different screening regimens for higher- and lower-risk women are as effective as existing annual screenings.
The women, none of whom had breast cancer, were randomized to receive either more personalized risk-based screening or 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 annual screening for breast cancer. This suggests that cancer was not missed by alternative screening schedules.
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The incidence of stage 2B breast cancer—the stage at which breast cancer mortality increases dramatically, three to eight times—was lower in the personalized screening group compared with those who received annual screening. “The number of stage 2B cancers has dropped by one-third, which is remarkable,” Esserman says. “Even I am amazed by these results.”
WISDOM also showed that changing screening schedules does not harm women by missing cancer. “This research is absolutely critical to implementing a risk-based approach,” says Esserman. “The first thing we had to do was prove it was safe.”
Esserman has long been concerned about uniform breast cancer screening guidelines. She and other experts have long known that women's risk for diseases varies widely, and as researchers have learned more about genetic risk factors, for example, they have discovered several mutations that appear to be associated with higher risk. Research also shows that not all women who develop breast cancer have a family history of the disease, which has traditionally been one of the risk factors doctors consider.
WISDOM's risk-based strategy included genetic testing of nine breast cancer genes. On their own, some of them have no significant effect on breast cancer risk, but collectively, studies link them to a higher risk. Other factors such as breast density, age and medical history of the woman as well as her family 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 their risk factors, and those at highest risk had mammograms and MRIs every six months. High-risk women underwent annual mammography; Women at average risk were prescribed mammograms every two years, and women at the lowest risk did not receive mammograms until their risk score changed.
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A more personalized, risk-based assessment allows for more targeted screening that could benefit women, Esserman said. Although the current study was designed only to demonstrate its safety, she plans to monitor the treatment and its results. “We are working to improve our risk reduction and risk prediction tools so we can improve our prevention efforts. [of breast cancer]”,” she says. Current screening methods are too broad and do not distinguish between high- and low-risk women, leading to overtreatment of some and no cancer in others. “We want to find people at the highest risk of developing cancer,” she says.
The key to using risk-based screening is a reliable algorithm that takes into account the latest knowledge about the main risk factors for the disease, which means challenging long-held views. The findings also make a strong case for routine genetic testing for women, starting at a relatively young age, Esserman says, since many of the highest-risk cases of breast cancer begin when women are in their 30s. For example, in the study, 30% of women with high-risk genes had no family history of breast cancer. “This surprised everyone, including us. It shows that family history is not a reliable way to determine who should get a genetic test,” Esserman says.
The study also found that women's expectations and preferences for breast cancer screening are changing. WISDOM was conducted during a pandemic that has changed people's thresholds for screening. “People thought, 'It would be good to know my risk so that I could decide whether I should enter into [for the screening] or not,’ and I think that helped us,” Esserman says. “People were more reluctant to consider screening less until COVID happened.”
The WISDOM results support other breast cancer studies that are examining the need for aggressive treatment of very early, low-grade cancers such as DCIS. Earlier this year COMET researchled by Dr. Shelley Hwang of Duke University, showed that for some women diagnosed with DCIS, close monitoring with more frequent mammograms did not lead to a higher risk of developing breast cancer than those who chose to have surgery and radiation therapy to remove the lesions.
The current results are just the beginning for WISDOM, which has already recruited women for the next phase, focusing on whether risk-based personalized screening can help prevent cancer. “I would really like to see this country adopt a comprehensive risk-based screening program,” Esserman says, noting that several countries in Europe, including Britain, France and the Netherlands, already rely on different versions of this approach. “It's very gratifying to get these results. The more screening, the better, the smarter the screening.”
