Contrast-enhanced MR Imaging as a Breast Cancer Screening in Women at Intermediate Risk

Study Overview
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Brief Summary
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A multicenter randomized controlled trial to evaluate the performance of MRI, in terms of sensitivity, specificity, and predictive value, in the screening of women at intermediate risk of breast cancer. Two surveillance programs will be compared. Women will be randomly assigned with a 1:1 ratio to: Yearly two-view mammography (Mx) and breast ultrasonography (US) or Yearly MRI.

Detailed Description
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Women, who, due to an increased risk of invasive breast cancer, are offered a specific surveillance program, as a supplement to the standard screening activities which in Italy are based on mammography every two years starting at age 50.Women will be randomly assigned to Yearly two-view mammography (Mx) and breast ultrasonography (US) or to Yearly MRI.

Official Title
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A Multicenter Randomised Trial of Contrast-enhanced MR Imaging as a Breast Cancer Screening Tool Alternative to Mammography and Ultrasonography in Women at Intermediate Risk. Feasibility, and Short Term Results.

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: Magnetic Resonance Imaging (MRI)
* Other: Mammography (Mx) + ultrasonography (US)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 40-59 years with cumulative risk at 10 years of at least 5%, or a lifetime cumulative breast cancer risk ranging between 15% and 30% (equivalent to a relative risk of 2-6 as compared to a low risk woman of the same age). The lifetime cumulative risk of breast cancer will be computed using the IBIS Breast Cancer Risk Evaluation Tool (http://www.ems-trials.org/riskevaluator/); or mammographic density involving more than 75% of the breast area, based on the most recent mammogram. The evaluation of the composition of the mammary gland will be performed using the BI-RADS classification. Women with mammography in class 4 (i.e., >75% of glandular component) will be eligible for randomization. Written Informed consent Exclusion Criteria: Signs or symptoms of breast cancer at enrolment; Previous diagnosis of ductal carcinoma in situ or invasive breast cancer; BRCA or p53 mutation carrier status; General contraindications to MRI (e.g. cardiac pacemaker, metal implants or history of severe allergic reaction after administration of contrast agent; Contraindications to any intravenous administration of contrast agent; Ongoing or planned pregnancy (for the duration of the study); Hormonal enhancement of ovarian function for assisted reproduction in the previous 3 years Presence of breast implants; Previous diagnosis of cancer at any site; Life-threatening diseases; Mental disability precluding informed consent to participate

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Magnetic Resonance Imaging (MRI)<br>Patients will undergo MRI yearly | Other: Magnetic Resonance Imaging (MRI)<br> <br> |
| Other: Mammography (Mx) + ultrasonography (US)<br>Patients will undergo yearly two-view (Mx) and breast US | Other: Mammography (Mx) + ultrasonography (US)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of in situ and invasive breast cancers detected in the two arms of the study | The performance of MRI will be evaluated , in terms of sensitivity, specificity, and predictive value, in the screening of women at intermediate risk of breast cancer | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients per each clinical and pathological stage of invasive cancer detected in the two arms of the study |  | 3 years | 
| Proportion of the different histological characteristics of cancers detected in the two arms |  | 3 years | 
| Number of invasive diagnostic procedures in the two study arms. |  | 3 years | 
| Number of interval cancers in the two study arms. |  | 3 years | 
| Rate of eligible women who accept to enter the study. |  | 3 years | 
| Compliance to the intervention in the two study arms. |  | 3 years | 
| Average and interquartile range of the risk profiles computed according to IBIS Breast Cancer Risk Evaluation Tool in the two arms |  | 3 years | 
| Number of cancers (in situ and invasive) detected in excess in the experimental arm compared to the conventional arm (overdiagnosis) after 10 years of follow up |  | 10 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, intermediate risk