Breast Cancer
Conditions
Keywords
Breast cancer, Imaging surveillance, Recurrence detection, Risk-stratified follow-up, MRI breast, Register-based randomized trial
Brief summary
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_TESTRisk-Stratified Imaging Surveillance
Surveillance using more sensitive breast imaging modalities such as MRI or contrast-enhanced mammography based on recurrence risk.
DIAGNOSTIC_TESTStandard Mammographic Surveillance
Routine follow-up with mammography according to current clinical guidelines.
Sponsors
Umeå University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| False Positive Findings | During the 5-year surveillance period | Number of surveillance findings leading to diagnostic workup without cancer diagnosis |
| 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 |
| 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 |
Contacts
CONTACTCharlotta Wadsten, Assoc Prof, MD
Outcome results
None listed