Since 2005 every woman in Germany aged 50 to 69 years has been invited to participate in mammography screening every two years. Whether and to what extent women aged 45 to 49 years and 70 to 74 years could also benefit from regular screening for breast cancer has now been investigated by the Institute for Quality and Efficiency in Health Care (IQWiG) in a benefit assessment commissioned by the Federal Joint Committee (G-BA).
Result: For both the younger age group and the older one, IQWiG sees an overall hint of a benefit from mammography screening versus no screening. Possible harms from false-positive findings or overdiagnosis are outweighed by a breast cancer-specific survival benefit.
IQWiG’s Director Jürgen Windeler emphasizes: "In both age groups, however, the advantage proven in studies is only very small for the individual woman. In this respect, an individual evaluation and weighing of benefits and harms remains essential. We should therefore do everything we can to ensure that women can make an informed decision about whether to undergo mammography – or not."
Expansion of the screening programme only possible after positive vote from the Federal Office for Radiation Protection
A mammography screening programme is a serial examination for the early detection of breast cancer in women. In Germany, it is offered to all 50- to 69-year-old women every two years. Currently, about half of these women participate in the German mammography screening programme.
In March 2021 the EU Commission updated the European Breast Cancer Guideline. The EU guideline now recommends that women between the ages of 45 and 49 and between the ages of 70 and 74 should also be included in a breast cancer screening programme. Against this background, in April 2021 the G-BA commissioned IQWiG to review the age limits in the German mammography screening programme.
Before the mammography screening programme can be expanded, the responsible Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection first has to determine the permissibility of this measure under radiation protection law. The Federal Office for Radiation Protection (BfS) is currently examining this on behalf of the ministry for both the upper and lower age limits.
The younger age group: good evidence base
IQWiG included eight randomized controlled trials with more than 600,000 participants in the benefit assessment of mammography screening for breast cancer in 45- to 49-year-old women. According to these studies, mammography screening in this age group prevents about 5 out of 10,000 women invited for screening from dying of breast cancer within ten years.
However, a mammogram can also have negative consequences for a woman with no suspicion of breast cancer; namely, if the findings are false-positive. The woman then worries unnecessarily and diagnostic clarification may cause complications. In each screening round, up to 340 out of 10,000 invited women between 45 and 49 years of age undergo invasive diagnostic clarification with subsequent benign findings. In addition, up to 41 out of 10,000 women invited for screening in this age group are diagnosed with breast cancer that would otherwise never have been noticed or caused problems. Such overdiagnosis leads to unnecessary surgery and radiation.
In the overall weighing of benefits and harms – fewer deaths from breast cancer versus false-positive findings and overdiagnosis – in IQWiG’s opinion the advantages of mammography screening for 45- to 49-year-old women outweigh those of no screening. In this regard, IQWiG's conclusion did not change between the preliminary and final report.
The older age group: IQWiG now also recommends screening
The evidence base is poorer for the benefit assessment of mammography screening in older women: only two randomized controlled trials with about 18,000 participants included women aged 70 years and older at baseline. In the preliminary report, IQWiG therefore concluded that the available data were insufficient for a conclusive weighing of benefits and harms.
After intensive discussion of the comments received on the preliminary report, the Institute now interprets the evidence base differently in the final report. According to the report, the evidence is now sufficient to also draw a conclusion on benefit for 70- to 74-year-old women and to recommend a corresponding expansion of the mammography screening programme.
The important Swedish study examined only a few 70- to 74-year-old women, so the results are not as clear and meaningful as for the middle-aged groups. In addition, the study's results suggest that the breast cancer-specific survival benefit may be somewhat smaller among 70- to 74-year old women than among 50- to 69-year-old women. IQWiG‘s Director Jürgen Windeler emphasizes: "However, there is no reason to assume that the effects of breast cancer screening are markedly different in the middle and older age groups. It should also be taken into account that this important study is already about 40 years old. Since then, however, the remaining life expectancy of 70-year-old women has increased from 13.5 years to 17 years. The consistent effect observed for the middle and older age groups is thus supported by the plausible assumption that 65- to 69-year-old women in the 1980s are equivalent in health status and life expectancy to today's 70- to 74-year-old women. Thus, the proven positive effect of screening on breast cancer-specific survival of the then 60- to 69-year-old women essentially applies to today's 70- to 74-year-old women."
In addition, the assumption of a positive screening effect on breast cancer-specific survival in 70- to 74-year-old women is further supported by a modelling study prepared for IQWiG by the private university UMIT Tirol: The modelling results appear sufficiently robust because they fit well with the results at the lower age limit, which are well documented (see above). In this respect, robustness can also be assumed for the upper age limit.
In summary, IQWiG now also assesses the benefit of mammography screening for 70- to 74-year-old women as higher than the related harm (false-positive findings and overdiagnosis).
Procedure of report production
IQWiG published the preliminary results in the form of the preliminary report in February 2022 and invited interested parties to submit comments. At the end of the commenting procedure, the project team revised the preliminary report and sent it as a final report to the commissioning agency, the G-BA, in July. The written comments submitted are published in a separate document at the same time as the final report.
An English-language extract of the published German-language report will by available on the IQWiG website by 12 September 2022.