Risk-based screening approaches can reduce over-detection, while self-testing and new diagnostics find early disease

_NATURE MEDICINE

In 2020, after a routine mammogram at her local clinic in the United Kingdom, 60-year-old Sally was invited to participate in a study on breast-cancer screening. She did not think twice before enrolling, remembering her best friend, who died from the disease at 30 years of age. “I would do anything I could to pick up any size of breast cancer earlier,” she says.

The study, called ‘My Personal Breast Screening’ (MyPebs), is a large-scale randomized trial enrolling 85,000 women 40–70 years of age in six countries — Belgium, France, Israel, Italy,
the United Kingdom and Spain — to evaluate the benefits of risk-based screening com-
pared with the current screening strategy in each country. As a first step, the researchers
analyzed Sally’s family history and hormonal status and ran a saliva-based DNA test to identify genetic variations known to be linked to breast cancer.

The result came as a shock: she was categorized as being at high risk for breast cancer. Sally quickly decided to make some lifestyle changes, losing weight and reducing her alcohol intake. But what really reassured her was the tailored screening strategy provided to her. Now, instead of getting mammograms every 3 years like everyone else in the United Kingdom, she will do the exam annually. “This put my mind at rest,” she says.

Age is not the only risk factor

For more than three decades, mass-population breast cancer screening worldwide has been based solely on one risk factor: age. Most programs and guidelines recommend mammography every 2 or 3 years for women 40–50 years of age (depending on the country) up to 74 years of age — regardless of other risk factors. Researchers at MyPebs believe they can improve screening by stratifying women according to their risk, on the basis of genetic factors, personal and familial history, and offering them a more personalized screening routine.

“What we do today in terms of breast cancer screening is a very outdated one-size-fits-all
strategy,” says Suzette Delaloge, MyPeb’s coordinator and oncologist at the cancer center Gustave Roussy in France. Delaloge notes that the current standard screening strategy is based on clinical trials from more than 25 years ago, when the population, risk factors, cancer incidence and treatments were different.

As a result of this broad approach to screening, some women at low risk of the disease are tested more often than they need to be, exposing them to the harms of screening, which can include radiation from mammograms, and unnecessary biopsies and treatment after over-diagnosis due to false-positive results. On the other hand, women at high risk are not screened frequently enough, which can lead to some fast-growing aggressive tumors going unnoticed.

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Nature Medicine volume 29, pages1587–1590 (2023)