European guidelines on breast cancer screening and diagnosis

For triple negative tumours and HER2-positive, evidence suggests that there is no additional benefit because of no increased risks from metastases.

The GDG suggests research to clarify the clinical significance of true positives (for all stages).

• For clinical stage II breast cancers, the GDG notes that there is no evidence of an increased detection rate according to hormone receptor and HER2 status, although these results might influence the decision to conduct further imaging because of the possible impact on treatment strategies.
• The GDG also notes that age and presence of comorbidities of the patient may be a consideration in the decision of whether to conduct staging exams with imaging as this may change the choice of treatment.
• Subgroups based on histological and marker results may impact the need to conduct staging examinations using imaging.

• The GDG notes that a positive on imaging staging exams may be managed differently in different settings and in different body sites; if the presence of a distant metastasis on staging exams results in initiation of treatment, the impact of false positives may be greater.
• The GDG considered the definition of ‘clinical stage’ as pre-pathological clinical stage, in accordance with the definition listed in the ECIBC glossary.
• The GDG notes that there is still uncertainty with the evidence of detection rate using staging exams with imaging.
• Consultation with colleagues during the interdisciplinary cancer treatment team meetings may be helpful in limiting the need for staging exams.
• Education of healthcare providers to limit the use of staging exams using imaging for clinical stage IIa/IIb breast cancer.

The GDG suggests monitoring for compliance that routine staging exams using imaging are not conducted due to the undesirable effects, including increased false positives with small desirable effects. 

• The GDG notes that no research evidence was identified on how people value the main outcomes. The GDG suggests additional research on how people value the main outcomes of staging exams for detection of metastases.
• The GDG suggests further research on marker results and the implications for using staging exams using imaging.
• Further research on the psychological effects and values and preferences for women related to the consequences of staging and non-staging approaches.

The conditional recommendation for stage IIa, is a result of a balance that favours the comparison (no staging exams) with very low certainty of the evidence, so we are not very certain as to what the benefits are. In addition there are large costs, probably reduced equity and the intervention is probably not feasible. The GDG felt that very few situations would arise that would prompt conducting a PET-CT.

The conditional recommendation for stage IIb, is a result of a balance that does not favour PET-CT, with very low certainty of the evidence. In addition, the same as in stage IIa, there are large costs, probably reduced equity and the intervention is probably not feasible.

The concern about metastases that would not give symptoms in the life of a patient increases as breast cancer stages become lower.

The GDG agreed that for stage IIb there are more scenarios (clinical presentations) that would lead the clinician/patient to opt for doing a PET-CT (tumour grade, age).

The GDG suggested the following:

• More knowledge on determining the probability of metastases that would not give symptoms in the life of a patient would improve describing the conditions for which PET-CT testing is indicated.
• Better characterisation of clinical tumour stages (stage IIa and stage IIb).

The GDG also notes that age and presence of comorbidities of the patient may be a consideration in the decision of whether to conduct staging exams with imaging as this may change the choice of treatment.

The GDG considered the definition of stage groups according to the American Joint Commission on Cancer TNM Anatomic Stage Groups (8th ed.) listed in the ECIBC glossary. 

The GDG suggests monitoring that women with clinical stage III breast cancer receive staging exams using imaging. 

• The GDG suggests research assessing the cause of false positive cases to minimize the number of false positives and the undue stress that this poses on patients with clinical stage III breast cancer.
• The GDG suggests research on non-ionizing and low-radiation dose alternatives for staging exams using imaging.

The conditional recommendation is a result of a balance of effects that probably favours the intervention (PET-CT) but has moderate costs and probably reduces equity. 

Need to take into account the resource capacity (including human resources and financial resources and equipment) across Europe.

• Need for cost-effectiveness data
• Need for studies evaluating follow-up of patients that would address patient important outcomes as the only data evaluated is on accuracy outcomes.