IRIS: Risk-Based Imaging After Breast-Conserving Surgery

The effectiveness of current breast cancer follow-up guidelines after curative treatment remains uncertain. Although early detection of local recurrences is associated with improved survival, particularly when identified through imaging rather than symptoms, evidence supporting the optimal intensity and modality of post-treatment surveillance is limited. Current follow-up recommendations are largely uniform, despite well-established variation in recurrence risk related to age, tumor subtype, surgical margins, adjuvant therapy, and breast density. Younger patients and those with non-luminal tumor subtypes have a substantially higher risk of recurrence.

Mammographic sensitivity is lower in breast cancer survivors compared with screening populations, and the incidence of interval cancers is significantly higher. Risk factors for interval-detected recurrences include young age, dense breast tissue, omission of radiotherapy after breast-conserving surgery, and biologically aggressive tumors. Supplemental imaging modalities such as magnetic resonance imaging (MRI) and contrast-enhanced mammography (CEM) have shown higher sensitivity and may improve detection in higher-risk groups, but current evidence is insufficient to support broad implementation of risk-based surveillance strategies.

This study is a multicenter, open-label, register-based randomized controlled trial designed to evaluate a stratified imaging surveillance approach after curative treatment for breast cancer. The objective is to determine whether the use of more sensitive imaging methods, compared with standard mammographic surveillance, results in earlier detection of ipsilateral recurrences and contralateral second primary breast cancers in patients with increased risk of recurrence following breast-conserving surgery.

The primary endpoint is the number of interval-detected ipsilateral recurrences and contralateral second primary breast cancers within five years from index breast cancer diagnosis. Secondary endpoints include stage at diagnosis, breast cancer-specific survival, overall survival, recall rate, biopsy rate, number of false positive findings, and health-related quality of life.

• Risk-Stratified Imaging Surveillance (Diagnostic test): Surveillance using more sensitive breast imaging modalities such as MRI or contrast-enhanced mammography based on recurrence risk.
• Standard Mammographic Surveillance (Diagnostic test): Routine follow-up with mammography according to current clinical guidelines.

Primary outcomes

• Interval Ipsilateral Recurrences and Contralateral Second Primary Breast Cancers [From index breast cancer diagnosis up to 5 years]: Number of ipsilateral breast cancer recurrences and contralateral second primary breast cancers detected between scheduled surveillance examinations.

Secondary outcomes

• Stage at Diagnosis of Recurrences and Second Primary Breast Cancers [Up to 5 years from index diagnosis]: Tumor stage at diagnosis of ipsilateral recurrences and contralateral second primary breast cancers
• Breast Cancer-Specific Survival [Up to 5 years from index diagnosis]: Survival without death attributed to breast cancer
• Overall Survival [Up to 5 years from index diagnosis]: Survival from any cause
• Recall Rate [During the 5-year surveillance period]: Proportion of surveillance examinations leading to recall for additional diagnostic assessment
• Biopsy Rate [During the 5-year surveillance period]: Number of biopsies performed following surveillance imaging
• False Positive Findings [During the 5-year surveillance period]: Number of surveillance findings leading to diagnostic workup without cancer diagnosis
• Health-Related Quality of Life [Baseline (pre-treatment), 6 months, 12 months, and 3 years after diagnosis.]: Measured using validated Patient-Reported Outcome Measures (PROM) questionnaires collected within the Swedish National Breast Cancer Quality Registry (Nationellt Kvalitetsregister för Bröstcancer).Patient-reported quality of life will be assessed using the EORTC QLQ-C30 (core cancer quality-of-life questionnaire) and the breast cancer-specific module QLQ-BR23, developed by the European Organisation for Research and Treatment of Cancer.Scores are calculated according to each instrument's scoring manual and transformed to standardized scales (0-100 or instrument-specific ranges). Higher scores indicate better function/global quality of life

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Histologically confirmed primary breast cancer
* Treated with breast-conserving surgery with curative intent
* Completed primary treatment according to clinical guidelines
* Classified as having increased risk of recurrence according to predefined study risk criteria (based on factors such as age, tumor subtype)
* Eligible for imaging surveillance
* Registered in participating national or regional breast cancer registry
* Able to comply with study follow-up procedures

Exclusion Criteria:

* Previous ipsilateral or contralateral invasive breast cancer within the last 5 years (except index cancer)
* Bilateral mastectomy
* Known metastatic breast cancer at time of enrollment
* Contraindication to contrast agents or MRI (if applicable for assigned arm)
* Ongoing pregnancy at time of randomization
* Any condition that, in the investigator's judgment, prevents participation in imaging surveillance