Recommendations from European Breast Guidelines

Should annual vs. triennial mammography screening be used for early detection of breast cancer in women aged 45 to 49?

Recommendation

For asymptomatic women aged 45 to 49 with an average risk of breast cancer, the ECIBC's Guidelines Development Group (GDG) suggests against annual mammography screening over triennial mammography screening in the context of an organised screening programme (conditional recommendation, very low certainty in the evidence).

Recommendation strength

  •   Strong recommendation against the intervention
  • Conditional recommendation against the intervention
  •   Conditional recommendation for either the intervention or the comparison
  •   Conditional recommendation for the intervention
  •   Strong recommendation for the intervention

A recommendation can be strong or conditional.

When a recommendation is strong, most women will want to follow it. When a recommendation is conditional, the majority of women want to follow it but may need more discussion with their healthcare professional first.

Subgroup

None were considered.

Justification

Overall justification

The recommendation was agreed by consensus.

The recommendation was conditional due to no net health benefits with annual screening and large costs associated with it.

Considerations

Implementation

The GDG agreed that the possibility of using other imaging techniques in this subgroup of women may be relevant to consider.

Monitoring and Evaluation

Evaluate existing programmes that already have in place annual screening in order to have data for inter-country comparability.

Research Priorities

1. The GDG agreed that more research on the effectiveness of the different screening intervals, comparative studies, would be helpful due to the small amount of evidence available and the very low certainty of it.

2. More reliable data is necessary, particularly in this age group, as the only data comes from a small trial where the mammograms were taken in 1987.

3. More research on the use of other imaging modalities was deemed by the GDG to be useful in this age group.

4. There was discussion in the GDG whether women with dense breasts in this age group should be screened at different intervals.

5. The use of more consistent modelling studies was also highlighted.

6. The GDG felt that increased cost effectiveness data, having more contextualised costs and cost-effectiveness analysis and from other settings would be helpful for future recommendations; this included checking the consistency of cost-effectiveness models with new research from trials on breast cancer screening and natural history of breast cancer disease. Also many member states have cost analysis but they are in the grey literature and not publicly available, and this should be shared with the scientific community. This priority may apply to all other screening interval recommendations.

Evidence

Download the evidence profile

Assessment

Background

Breast cancer is the second most common cancer in the world and the most frequent cancer among women with an estimated 1.67 million new cancer cases diagnosed in 2012 (25% of all cancers) (Ferlay J, 2013). In 2018 in Europe, it is estimated that 41,449 women between the ages of 45 and 49 will be diagnosed with breast cancer and 5,680 will die (Ferlay, 2018). Mammography screening has both potential benefits and harms. The Guidelines Development Group has conditionally recommended against screening in women between the ages of 40 and 44, but conditionally for screening for women between the ages of 45 and 49.
Debate about the recommended interval for screening with mammography remains due to the theoretical advantage of earlier diagnosis but a potential increase in harms with shorter screening intervals. For example, the USPSTF recommended to individualise the decision of screening (AL et al., 2016) in women aged 40 to 49 years, while the ACS recommended annual screening between the ages of 45 and 54 (Myers, 2015).

Management of Conflicts of Interest (CoI): CoIs for all Guidelines Development Group (GDG) members were assessed and managed by the Joint Research Centre (JRC) following an established procedure in line with European Commission rules. GDG member participation in the development of the recommendations was restricted, according to CoI disclosure. Consequently, for this particular question, the following GDG members were recused from voting: Roberto d'Amico and Chris de Wolf. Miranda Langendam, as external expert, was also not allowed to vote, according to the ECIBC rules of procedure.
For more information please visit http://ecibc.jrc.ec.europa.eu/gdg-documents

Is the problem a priority?
Yes *
* Possible answers: ( No , Probably no , Probably yes , Yes , Varies , Don't know )
Research Evidence
Breast cancer is the second most common cancer in the world and, by far, the most frequent cancer among women with an estimated 1.67 million new cancer cases diagnosed in 2012 (25% of all cancers) (Ferlay et al., 2013). Breast cancer ranks as the fifth cause of death from cancer overall (522,000 deaths) and it is the second cause of cancer death in developed regions (198,000 deaths, 15.4%) after lung cancer. In 2018 in, Europe, it is estimated that 41,449 women between the ages of 45 and 49 will be diagnosed with breast cancer and 5,680 will die (Ferlay, 2018). Breast cancer is the fourth cancer with the highest disease burden (Tsilidis KK, 2016).

Although mammography screening is generally accepted as beneficial in reducing breast cancer mortality in women 50-69 years. The balance between benefits and harms for the different screening intervals is still debatable with recommended periodicity varying between annual to triennial. In the group of women aged between 45 to 49, the amount of evidence is even more scarce and the topic is controversial.
Additional Considerations

This question was prioritised by the GDG.

How substantial are the desirable anticipated effects?
Small *
* Possible answers: ( Trivial , Small , Moderate , Large , Varies , Don't know )
Research Evidence


Additional Considerations

Events in the modelling study (QALY) were calculated by subtracting estimation of 45 to 69 screening years minus 50 to 69 screening years. Effects are then incremental to the 50 to 69 screening, and may vary by the year of last screening.

For the 50 to 69 years age group, one randomised trial in the United Kingdom did not show higher risk of breast cancer mortality with triennial screening (Breast Screening Frequency Trial, 2002); observational studies from the United States reported larger proportions of interval cancer and lower proportions of false positive adverse events in the triennial schedule.

The GDG noted inconsistency in different studies providing data on breast cancer mortality and QALYs for annual vs triennial mammography screening in the ages 45-49. While there were more breast cancer deaths and a greater number of false positives with annual screening, there were increased QALYs presented in the modelling data for annual vs triennial.

The model data was considered to be unstable in the age range 45 to 49 years old. It was considered that the model used was not internally consistent, and therefore, the GDG agreed they could not rely only on this data for this recommendation.

The GDG noted that there were fewer interval cancers (based on the study by (Klemi, 1997)). There was significant concern by the GDG in the data quality.

The GDG also noted that there is concern with the denominators used. In the actual study there were very few number of cancers detected, but the data was extrapolated in order to present it as a rate per 100,000 breast cancers. Based on the actual events in the study, this would be equivalent to approximately 25 fewer cancers per 100,000 women screened.

As agreement within the GDG could not be reached, voting among the members without CoI resulted in the following: two members voted "trivial" and 20 members voted "small"

How substantial are the undesirable anticipated effects?
Moderate *
* Possible answers: ( Large , Moderate , Small , Trivial , Varies , Don't know )
Research Evidence