In France, the participation rate in the national organized screening program is far from reaching the objectives. It is below 50% well below the expected rate of 70%. Should the mode of organization be changed?
The breast cancer screening strategy is based on an organized national program, led by INCa, offering bilateral mammography with double reading every two years in women aged 50 to 74 at average risk. This organization is supported by the High Authority for Health (HAS), which nevertheless highlights the limits of screening based solely on age, in particular overdiagnosis, false positives and inequalities in benefit depending on the level of individual risk. In this context, the American WISDOM trial (Women Informed to Screen Depending on Measures of Risk), published in JAMAprovides important data on a personalized screening strategy integrating clinical and genetic factors.
WISDOM is a pragmatic randomized clinical trial including women aged 40 to 74 years with no history of breast cancer. Participants were randomized between standard annual screening and screening based on individual risk.
The risk assessment in the intervention group was based on a model combining:
- a recognized clinical model (Breast Cancer Surveillance Consortium version 2),
- a polygenic risk score calculated from hundreds of genetic variants (SNVs),
- carrier status of a high penetrance variant.
Four levels of risk defined the screening recommendations:
- Very high risk (≥ 6% risk at 5 years or pathogenic variant): screening alternating mammography and MRI every 6 months + risk reduction advice;
- High risk: annual mammogram + advice;
- Medium risk: mammogram every two years;
- Low risk: no screening until risk returns to a threshold ≥ 1.3% or until age 50.JAMA Network
In the standard annual group, all women were invited for annual mammography without modification of frequency based on risk.
The rate of stage ≥ IIB breast cancer: no difference between the two groups.
Primary result, the rate of stage ≥ IIB breast cancers was non-inferior in the risk-based screening group compared to annual screening. The difference in rates (–18 cases per 100,000 person-years) did not reach statistical significance but confirms that individualized screening does not increase the number of advanced cancers.
In contrast, risk-based screening did not reduce the biopsy rate overall, despite a significant decrease in the number of mammograms performed. This is explained in particular by less adherence than expected to screening recommendations adapted to risk. Some low-risk women still had frequent mammograms, and some high-risk women had more MRIs than expected.
As expected, the number of mammograms was significantly lower in the risk-based screening group (difference of approximately –3836 mammograms per 100,000 person-years). However, increased use of MRI and biopsies in higher risk categories has partially offset these savings.
The personalized approach was well accepted: in the observational cohort, 89% of women chose risk-based screening when given the choice.
High acceptance of the approach
The WISDOM trial demonstrates that risk-based screening is non-inferior to annual screening in terms of advanced breast cancers, suggesting no loss of chance in the medium term. The number of mammograms was significantly reduced in the personalized group, with no overall reduction in biopsies. The acceptability of the individualized approach was high, consistent with the findings of the HAS on the importance of information and shared decision-making in screening.
The WISDOM results support the recent directions of the HAS and the INCa in favor of an evolution of screening towards a more personalized approach, based on the level of risk. The integration of genetic tools could, ultimately, improve the identification of women requiring increased monitoring while limiting over-screening in low-risk women. However, several challenges remain: validation of genetic tools in the French population, equity of access, organization of the care pathway, training of professionals and medico-economic evaluation, central point for any modification of the national program.
The comparison between WISDOM and the French system must remain cautious. The comparator of the trial (annual screening) differs from the French biennial organized screening. Screening is initiated from the age of 40 and not 50 as in France. Furthermore, neither specific mortality nor long-term costs are yet available, although these criteria are essential in the public health decisions made by the HAS.
Ultimately, the WISDOM trial provides solid proof of concept for breast cancer screening based on individual risk. In line with the current thinking of the HAS and the INCa. It supports the idea of a gradual evolution of organized screening towards finer risk stratification, ultimately integrating genetic data, subject to additional validations and a rigorous assessment of the population impact.
