A New Study Challenges the Way We Screen for Breast Cancer

A much-anticipated study shows that screening for breast cancer with annual mammograms is not always the best way to contract 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 programs based on a woman’s risk of developing the disease could be just as effective in detecting cancer.

Esserman launched the WISDOM (Women Informed to Screen Dependent on Measures of Risk) study in 2016 to explore whether more personalized assessments of a woman’s risk of developing breast cancer could lead to alternative screening programs that would be more helpful to them than uniform annual mammograms. Initial results, involving more than 28,000 women aged 40 to 74, suggest that different screening regimens for women at higher and lower risk are as effective as existing annual screenings.

The women, none of whom had breast cancer, were randomly assigned to receive either more personalized risk-based screening or annual screening. They were followed for about five years on average to see if they developed the disease. In this first analysis, Esserman and his team found that alternative screening regimens, including more or less frequent screening, were similar to annual screening for detecting breast cancer. This suggests that cancers have not been missed thanks to alternative screening programs.

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The number of stage 2B breast cancers – the stage at which deaths from breast cancer increase sharply, from three to eight times – was lower in the group receiving personalized screening than in the group receiving annual screening. “There’s been 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 changing the screening schedule did not harm women by missing cancers. “This study is absolutely a prerequisite for implementing a risk-based approach,” says Esserman. “The first thing we had to do was show that it was safe.”

Esserman has long been bothered by uniform breast cancer screening guidelines. She and other experts have long known that women have widely varying disease risks, 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. Studies also show that not all women who develop breast cancer have a family history, which is traditionally one of the risk factors considered by doctors.

WISDOM’s risk-based strategy included genetic testing of nine breast cancer genes. Alone, some have no appreciable effect on breast cancer risk, but together, research links them to higher risk. Other factors, such as breast density, age and disease history of the woman and her family, were also included. Based on these risks, Esserman’s team developed an algorithm to assign women to one of four different screening regimens. All women received counseling on risk factors, and women at highest risk underwent alternating mammograms and MRIs every six months. Women at high risk had annual mammograms; Women at average risk received mammograms every two years, and those at the lowest risk did not receive mammograms unless their risk score changed.

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The more personalized risk-based assessment allows for more targeted screening that could benefit women, Esserman says. Although the current study was simply designed to demonstrate its safety, it plans to track treatments and outcomes. “We are working to improve our risk reduction tools and predict risks to 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 for some and no cancers for others. “We want to find the people who are at the highest risk of cancer,” she says.

The key to the use of risk-based screening is a robust algorithm that incorporates the latest knowledge about the main risk factors for the disease, which requires revising long-held views. The findings also argue for routine genetic testing of women, starting at a relatively early age, Esserman says, because many high-risk breast cancers appear when women are around 30 years old. In the study, for example, 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 undergo genetic testing,” says Esserman.

The study also showed that women’s expectations and preferences regarding breast cancer screening are changing. WISDOM was conducted during the pandemic, which changed the thresholds for testing people. “People thought, ‘It would be good to know my risk to know if I should go’ [for the screening] or not,’ and I think that helped us,” Esserman says. “People were more reluctant to consider reducing testing until COVID came along.”