IRIS: Risk-Based Imaging After Breast-Conserving Surgery (IRIS)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Diagnostic test: Risk-Stratified Imaging Surveillance; Diagnostic test: Standard Mammographic Surveillance

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.

• Study Type: Interventional
• Enrollment (Estimated): 2300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charlotta Wadsten, Assoc Prof, MD; Phone Number: +4660181000; Email: charlotta.wadsten@umu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Risk-Stratified Imaging Surveillance; Participants receive risk-stratified post-treatment imaging surveillance using more sensitive imaging modalities (such as MRI or contrast-enhanced mammography) according to predefined risk criteria, instead of standard mammographic follow-up.	Diagnostic test: Risk-Stratified Imaging Surveillance; Surveillance using more sensitive breast imaging modalities such as MRI or contrast-enhanced mammography based on recurrence risk.
Active Comparator: Standard Mammographic Surveillance; Participants receive standard post-treatment imaging surveillance with mammography according to current clinical follow-up guidelines after breast-conserving surgery.	Diagnostic test: Standard Mammographic Surveillance; Routine follow-up with mammography according to current clinical guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interval Ipsilateral Recurrences and Contralateral Second Primary Breast Cancers	Number of ipsilateral breast cancer recurrences and contralateral second primary breast cancers detected between scheduled surveillance examinations.	From index breast cancer diagnosis up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage at Diagnosis of Recurrences and Second Primary Breast Cancers	Tumor stage at diagnosis of ipsilateral recurrences and contralateral second primary breast cancers	Up to 5 years from index diagnosis
Breast Cancer-Specific Survival	Survival without death attributed to breast cancer	Up to 5 years from index diagnosis
Overall Survival	Survival from any cause	Up to 5 years from index diagnosis
Recall Rate	Proportion of surveillance examinations leading to recall for additional diagnostic assessment	During the 5-year surveillance period
Biopsy Rate	Number of biopsies performed following surveillance imaging	During the 5-year surveillance period
False Positive Findings	Number of surveillance findings leading to diagnostic workup without cancer diagnosis	During the 5-year surveillance period
Health-Related Quality of Life	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	Baseline (pre-treatment), 6 months, 12 months, and 3 years after diagnosis.

Collaborators and Investigators

• Sponsor: Umeå University

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): January 1, 2034
• Study Completion (Estimated): January 1, 2034

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 16, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): February 23, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer; Recurrence detection; Imaging surveillance; Risk-stratified follow-up; MRI breast; Register-based randomized trial
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: Swe-BC-IRIS2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data may be shared upon reasonable request and after approval by the study steering committee, in accordance with applicable regulations and data protection laws.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No