Clinical trial NCT05675085: Risk-Based Breast Screening in Young Women
Official title: Risk-Based Breast Screening (RIBBS) in Young Women: Personalized Imaging Protocols
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Neoplasms
Keywords: Breast Neoplasms
Cancer Screening
Personalized Medicine
Mammographic Breast Density
Risk Assessment
Lead sponsor: Istituto Oncologico Veneto IRCCS
Sponsor class: OTHER
Collaborators: name: Regione del Veneto (Italy)
First posted: 2023-01-09
Enrollment: 10269
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.

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

Primary outcomes:
measure: Cumulative Incidence of Advanced Cancers
timeFrame: Up to 15 years
Secondary outcomes:
measure: Recall rate (RR)
timeFrame: Up to 6 years
measure: Cancer detection rate (CDR)
timeFrame: Up to 6 years
measure: Proportional Incidence of Interval Cancer
timeFrame: Up to 8 years
measure: Total Assessment Rate
timeFrame: Up to 6 years
measure: Surgical Referral Rate
timeFrame: Up to 6 years
measure: Surgery Rate
timeFrame: Up to 6 years
measure: Benign Lesion Detection Rate
timeFrame: Up to 6 years
measure: Tumor-Stage Specific Detection Rate
timeFrame: Up to 6 years
measure: Regular Re-Screening Rate
timeFrame: Up to 6 years
Other outcomes:
measure: Cost and Organizational Impact Analysis
timeFrame: Up to 8 years
measure: Impact of Breast Cancer Risk Model on Personalization of Screening
timeFrame: Up to 8 years
measure: Impact of Breast Density Metrics on Personalization of Screening
timeFrame: Up to 8 years
measure: Impact of Different Breast Density Metrics on Breast Cancer Risk Assessment
timeFrame: Up to 8 years
measure: Prevalence Analysis of Breast Cancer Subtypes
timeFrame: Up to 8 years
measure: Potential of Artificial Intelligence (AI) to Support Screening Personalization
timeFrame: Up to 8 years
Locations:
city: Padova
country: Italy
facility: Istituto Oncologico Veneto (IRCCS)
Study officials:
affiliation: Istituto Oncologico Veneto IRCCS
name: Francesca Caumo, MD
role: PRINCIPAL_INVESTIGATOR
References: