RIBBS: Risk-Based Breast Screening in Young Women
Study Details
Study Description
Brief Summary
The RIBBS study is a single-arm single-center study that aims to evaluate the effectiveness of a risk-based breast screening model using digital breast tomosynthesis (DBT) as the baseline test, quantitative individual breast density to guide supplemental ultrasound (US) imaging for dense breasts, and individual risk (calculated taking into account breast density) to guide the screening interval (annual or biennial).
Invited 45-year-old women are differentiated into five different screening protocols (based on breast density and risk), and screened according to a personalized model until they turn 50 and return to routine screening.
The primary endpoints (cancer detection rate, recall rate, and incidence of advanced breast cancers) will be measured at the end of the five-year intervention.
The results of the personalized screening model will be compared with those obtained from a neighboring region applying a "one-size-fits-all" model with annual mammography for women aged 45-49 years.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Detailed Description
The incidence of breast cancer in women aged 45 to 49 is not much lower than in women aged 50 to 54. However, while the Italian Health System offers mammography screening to all women aged 50 to 69 every two years, women aged 45 to 49 are invited for annual mammography screening in only a few regions. Breast density, i.e. the amount of fibroglandular tissue, more present in young women, decreases the performance of mammography by reducing the detectability of breast cancer; consequently, breast cancer in women with dense breasts can often be found only when it is larger and thus at a more advanced stage. In addition, breast density is an independent risk for breast cancer.
The RIBBS study was designed to use the first round of screening to identify women with dense breasts and those at increased risk of breast cancer, and use this information to tailor the subsequent screening protocol, including supplemental US imaging for women with dense breasts, and establishing the frequency of screening cycles according to risk category.
The reference imaging is digital breast tomosynthesis, which has already demonstrated greater sensitivity than digital mammography in the "standard" screening age (50-69).
Volumetric breast density (VBD) is calculated from DBT, and lifetime risk (LTR) is obtained from the Tyrer-Cuzick risk model which also includes breast drnsity as a risk factor.
After the first round of screening, women are divided into five groups: women with non-dense breasts and low breast cancer risk are screened every two years with DBT alone; women with dense breasts and low breast cancer risk are screened every two years with DBT plus additional ultrasound (DBT+US); women with non-dense breasts and intermediate risk of breast cancer are screened annually with DBT alone; women with dense breasts and intermediate risk of breast cancer are screened annually with DBT+US; finally, high-risk women with a family history of breast cancer (w/wo hereditary factors) are monitored with annual MRI and tomosynthesis.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: RIBBS arm This clinical trial is a single-arm study in which asymptomatic 45-year-old women undergo a triple screening test: (1) two-view tomosynthesis of both breasts; (2) calculation of volumetric breast density (VBD); (3) assessment of breast cancer risk using the Tyrer-Cuzick model. Mean VBD and lifetime risk (LTR) are used to determine the type of imaging and frequency of subsequent screening cycles. |
Diagnostic Test: Personalized screening protocol
At the first screening round (recruitment) all participating women had the same tests;
Two-view tomosynthesis of both breasts
Calculation of volumetric breast density (VBD)
Calculation of lifetime risk (LTR) using the Tyrer-Cuzick model
At subsequent rounds:
Women with non-dense breasts and low breast cancer risk are re-screened only with DBT every 2 years;
Women with dense breasts and low breast cancer risk are re-screened with DBT+US every 2 years;
Women with non-dense breasts and intermediate breast cancer risk are re-screened only with DBT every year;
Women with dense breasts and intermediate breast cancer risk are re-screened with DBT+US every year;
Women at high risk of breast cancer associated with a family history of breast cancer (w/wo hereditary factors) undergo DBT and MRI every year.
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Outcome Measures
Primary Outcome Measures
- Cancer detection rate (CDR) [Up to 6 years]
Number of cancers detected by screening test(s) per thousand women screened
- Recall rate (RR) [Up to 6 years]
Proportion of women recalled after the screening test for further workup after the screening test (BI-RADS abnormal interpretation rate)
- Cumulative Incidence of Advanced Cancers [Up to 6 years]
Proportion of breast cancers staged II or greater during the entire personalized screening period
Secondary Outcome Measures
- Cost-effectiveness analysis of the personalized screening model [Up to 6 years]
Quality-adjusted life year (QALY) of the personalized screening model compared to the "one-size-fits-all" model
- Interval cancers in the personalized screening model [Up to 6 years]
Interval cancers are cancers diagnosed between a negative screening episode - [mammogram classified as normal (BI-RADS ACR 1 or 2 or equivalent) or abnormal mammogram but negative assessment] and the next planned mammogram.
- Impact of breast cancer risk model on personalization of screening [Up to 6 years]
Comparison of percentages of women categorized as low, intermediate, and high risk for breast cancer using different risk models (Tyrer-Cuzick, Gail, Boadicea).
- Impact of breast density metrics on personalization of screening [Up to 6 years]
Comparison of percentages of women with dense and non-dense breasts using different breast density metrics (volumetric breast density, area-based breast density, BIRADS-equivalent).
- Impact of breast density metrics in risk-assessment [Up to 6 years]
Comparison of the proportions of women classified as low, intermediate and high risk for breast cancer provided by the Tyrer-Cuzick risk model using different metrics for breast density (VBD, ABD, BIRADS-equivalent).
- Prevalence of breast cancer subtypes [Up to 6 years]
Prevalence of breast cancer subtypes (luminal A, luminal B, HER2+, basal-like) overall and stratified by density and risk category.
- Potential of artificial intelligence (AI) to support personalization of screening [Up to 6 years]
Retrospective comparison of AI and double reading performance and stratification by breast density and risk categories.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Female
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Aged 45 years old
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Resident in the provinces of Padua and Rovigo (Italy)
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Willing and able to give written informed consent
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Willing and able to comply with scheduled visits, tests, and other procedures
Exclusion Criteria:
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Personal history of breast carcinoma, either invasive or ductal carcinoma in situ (DCIS)
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Known BRCA carrier or PALB2 or ≥50% risk
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Psychiatric or other disorders that are not compatible with compliance to the protocol requirements and follow-up
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Pregnant or breastfeeding
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Unable to give informed consent
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Current participation in another interventional breast screening trial
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Istituto Oncologico Veneto (IRCCS) | Padova | Italy | 35128 |
Sponsors and Collaborators
- Istituto Oncologico Veneto IRCCS
- Regione del Veneto (Italy)
Investigators
- Principal Investigator: Francesca Caumo, MD, Istituto Oncologico Veneto IRCCS
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RIBBS 2019/37