The benefit of risk-based breast cancer screening is still unclear

The Austrian Institute for Health Technology Assessment (AIHTA) investigated whether risk-based breast cancer screening has advantages over conventional age-based screening programs. The main result: The current prediction models cannot satisfactorily predict the individual breast cancer risk.

Only large studies currently underway will provide robust data on whether women can expect health benefits over conventional practice. “Such a system definitely requires extensive preparation. Simply assessing risk factors in women without thinking about further consequences is of no use to women,” says Ingrid Zechmeister-Koss, deputy director of the AIHTA.

Breast cancer is the most common cancer in women worldwide. In Austria there were 5,682 new cases and 1,643 deaths in 2019. Therefore, an age-related screening program is offered in most countries. The aim is to diagnose cancer as early as possible and to reduce surgical procedures such as removal of the entire breast (mastectomy) and the number of deaths from breast cancer. However, to date there is no consensus on the age and intervals at which mammography should be performed.

While most European countries recommend mammograms every two or three years for women aged 50 to 69, the United States recommends annual or biennial screening for women aged 45 to 74. In Austria, a population-based breast cancer screening program was introduced in January 2014, inviting women aged 45-69 to have a mammogram every two years.

Given conflicting research on the benefits and harms of such population-based breast cancer screening, the accuracy of such programs has long been debated. “There is no doubt that mammography can lead to false negative results as well as false positive breast cancer suspicions, leading to unnecessary biopsies and therapy,” says Ingrid Zechmeister-Koss from AIHTA.

The Austrian Health Insurance Fund (ÖGK) and the Medical Association are now considering changing the existing breast cancer screening program – for example offering a risk assessment. The AIHTA was therefore asked to conduct a systematic review to examine the quality of risk prediction models and the benefit of risk-based screening. In addition, the organizational requirements for the introduction of such a program were determined.

Several risk factors to consider

In contrast to age-based early breast cancer detection, risk-based screening takes into account several risk factors in addition to age, such as breast cancer in the family history, breast density, hormonal factors, body mass index or genetic markers. With the help of so-called risk prediction models, the probability that a woman will develop breast cancer within a certain period of time is estimated.

The resulting screening strategy, for example the frequency of mammograms, is determined according to this risk. The aim is to use an age-appropriate program to detect breast cancer earlier or at least as well and to reduce the disadvantages of conventional check-ups. For example, through less frequent mammograms in women with a low breast cancer risk or more frequent mammograms and other diagnostic options in women with an increased risk.

No randomized controlled trials completed yet

Altogether, AIHTA identified 107 studies from eight systematic reviews that examined the prognostic quality of risk prediction from seven prediction models. These models could not adequately predict the individual breast cancer risk in the observational studies. Even when more information about other risk factors – like breast density – was added, the quality of the predictions didn’t increase enough.

Completed randomized control studies that show the benefit-harm ratio of a risk assessment compared to conventional breast cancer screening are not yet available. In the currently ongoing randomized controlled MyPeBS study, risk-based screening is compared with conventional breast cancer screening strategies in several European countries. The results are not expected until 2026 at the earliest.

Systematic implementation and additional resources required

Before a switch to risk-based screening can take place, not only well-founded data on the benefit-harm ratio is required, but also detailed preparations in advance of the introduction: For example, it must be defined in advance which and how many risk factors are to be collected and to what extent will. “It’s not enough if the doctor asks about a few risk factors. A standardized tool is needed that can be used to systematically record the individual risk factors and to define a method for measuring breast density,” explains Zechmeister-Koss.

It must also be determined in advance who will carry out the risk assessment. This can be general practitioners, gynaecologists, specially trained nurses or the woman herself. In addition, it must be clarified before implementation which prediction model is to be used. According to the AIHTA report, it should be noted that not every model is suitable for every population. Many of the analyzed models have only been validated for specific age groups or populations.

Based on the risk assessment, the applied model calculates a risk score that indicates the probability of developing breast cancer in a certain period of time. “However, the risk score alone is of no benefit to the women. Thresholds need to be established at what five, ten, or lifetime risk a woman falls into a high, intermediate, or low risk group. Women need to be well-informed about the importance of a 10 percent risk Low-risk women need to be given a thorough and substantiated explanation that a longer screening interval does not mean they are being deprived of a benefit, it means their health benefit because so overdiagnosis, false alarms and unnecessary exposure to radiation can be prevented. This also means that doctors need a lot of training in professional advice and information campaigns,” explains study leader Irmgard Frühwirth.

In addition to the prognostic quality of the prediction models, the successful use of a risk-based screening strategy largely depends on “whether the risk-based screening recommendations and preventive interventions are effective, appropriate, accessible, feasible and acceptable,” the AIHTA report concludes.

Provided by the Austrian Institute for Health Technology Assessment GmbH