IRIS: Risk-Based Imaging After Breast-Conserving Surgery

Official title

Individualized Riskbased Imaging Surveillance After Breast-conserving Surgery for Breast Cancer (IRIS)- a Multicenter Randomized Trial

Overview

Breast cancer follow-up after curative treatment is currently based on largely uniform imaging surveillance strategies, despite substantial variation in recurrence risk across patient subgroups. Early detection of recurrences improves prognosis, particularly when detected by imaging rather than symptoms, but the optimal surveillance approach remains uncertain. Mammographic sensitivity is lower in breast cancer survivors than in screening populations, and interval cancers occur more frequently, especially among younger patients, those with dense breasts, aggressive tumor subtypes, or without radiotherapy after breast-conserving surgery. This multicenter, open-label, register-based randomized controlled trial evaluates risk-stratified imaging surveillance after breast-conserving surgery for breast cancer. The study investigates whether more sensitive imaging methods, compared with standard mammographic follow-up, lead to earlier detection of ipsilateral recurrences and contralateral second primary breast cancers in patients at increased risk of recurrence. The primary endpoint is the number of interval ipsilateral recurrences and contralateral second primary breast cancers detected within five years from index diagnosis. Secondary endpoints include stage at detection, breast cancer-specific survival, overall survival, recall rate, biopsy rate, false positive findings, and health-related quality of life.

Detailed description

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.

Interventions

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

Primary outcome measures

• Interval Ipsilateral Recurrences and Contralateral Second Primary Breast Cancers [Time frame: From index breast cancer diagnosis up to 5 years]

Secondary outcome measures (7)

• Stage at Diagnosis of Recurrences and Second Primary Breast Cancers [Time frame: Up to 5 years from index diagnosis]
• Breast Cancer-Specific Survival [Time frame: Up to 5 years from index diagnosis]
• Overall Survival [Time frame: Up to 5 years from index diagnosis]
• Recall Rate [Time frame: During the 5-year surveillance period]
• Biopsy Rate [Time frame: During the 5-year surveillance period]
• False Positive Findings [Time frame: During the 5-year surveillance period]
• Health-Related Quality of Life [Time frame: Baseline (pre-treatment), 6 months, 12 months, and 3 years after diagnosis.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07426510 · Swe-BC-IRIS2026

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗