Risk-Based Breast Screening in Young Women

NCT ID: NCT05675085

Last Updated: 2023-10-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10269 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-20
• Study Completion Date: 2026-01-31

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 only primary endpoint in this study is the cumulative incidence of advanced breast cancers (stage II and above). This endpoint will be evaluated at the end of the five-year intervention period and at 10 years.

The results of the personalized screening model will be compared with those obtained from an observational cohort from a neighboring region in which a "one-size-fits-all" approach involving annual mammography for women aged 45-49 years is used. The comparison will be conducted with the hypothesis of superiority of the personalized screening model.

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.

Our study hypothesizes that a screening model stratified by breast density and risk is more effective and sustainable in reducing the incidence of advanced breast cancer than standard annual mammography screening.

Conditions

Breast Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SCREENING
• Blinding Strategy: NONE

Study Groups

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.

Group Type: OTHER

Personalized screening protocol

Intervention Type: DIAGNOSTIC_TEST

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:

1. Women with non-dense breasts and low breast cancer risk are re-screened only with DBT every 2 years;

2. Women with dense breasts and low breast cancer risk are re-screened with DBT+US every 2 years;

3. Women with non-dense breasts and intermediate breast cancer risk are re-screened only with DBT every year;

4. Women with dense breasts and intermediate breast cancer risk are re-screened with DBT+US every year;

5. 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.

Interventions

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:

1. Women with non-dense breasts and low breast cancer risk are re-screened only with DBT every 2 years;

2. Women with dense breasts and low breast cancer risk are re-screened with DBT+US every 2 years;

3. Women with non-dense breasts and intermediate breast cancer risk are re-screened only with DBT every year;

4. Women with dense breasts and intermediate breast cancer risk are re-screened with DBT+US every year;

5. 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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Female
• Aged 45 years old
• Resident in the provinces of Padua and Rovigo (Italy)
• Willing and able to give written informed consent
• Willing and able to comply with scheduled visits, tests, and other procedures

Exclusion Criteria

• Recent mammography
• Personal history of breast carcinoma, either invasive or ductal carcinoma in situ (DCIS)
• Known BRCA carrier or PALB2 or ≥50% risk
• Psychiatric or other disorders that are not compatible with compliance to the protocol requirements and follow-up
• Pregnant or breastfeeding
• Unable to give informed consent
• Current participation in another interventional breast screening trial

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Regione del Veneto (Italy)

UNKNOWN

Sponsor Role: collaborator

Istituto Oncologico Veneto IRCCS

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francesca Caumo, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Oncologico Veneto IRCCS

Locations

Istituto Oncologico Veneto (IRCCS)

Padua, , Italy

Countries

Italy

References

Caumo F, Gennaro G, Ravaioli A, Baldan E, Bezzon E, Bottin S, Carlevaris P, Ciampani L, Coran A, Dal Bosco C, Del Genio S, Dalla Pieta A, Falcini F, Maggetto F, Manco G, Masiero T, Petrioli M, Polico I, Pisapia T, Zemella M, Zorzi M, Zovato S, Bucchi L. Personalized screening based on risk and density: prevalence data from the RIBBS study. Radiol Med. 2025 May;130(5):740-752. doi: 10.1007/s11547-025-01981-5. Epub 2025 Mar 21.

Reference Type: DERIVED

PMID: 40117106 (View on PubMed)

Gennaro G, Bucchi L, Ravaioli A, Zorzi M, Falcini F, Russo F, Caumo F. The risk-based breast screening (RIBBS) study protocol: a personalized screening model for young women. Radiol Med. 2024 May;129(5):727-736. doi: 10.1007/s11547-024-01797-9. Epub 2024 Mar 21.

Reference Type: DERIVED

PMID: 38512619 (View on PubMed)

Other Identifiers

RIBBS 2019/37

Identifier Type: -

Identifier Source: org_study_id