Breast Cancer Risk From Sonographic Glandular Tissue Component (or International GTC Study)

Recruiting

• Conditions: Screening; Breast Cancer

• Registration Number: NCT05460975
• Lead Sponsor: Seoul National University Hospital

Brief Summary

An international multicenter study to prospectively validate the association between sonographic GTC and subsequent breast cancer risk in women with dense breasts.

Detailed Description

Women with similarly dense breasts on mammography may have different subsequent risks of developing breast cancer due to varying degrees of lobular involution. Breast ultrasound (US) can assess the relative amount of glandular tissue component (GTC) to the fibrous stroma in dense breast parenchyma and can reflect the amount of terminal duct lobular units (TDLU) as seen in histology. In women with dense breasts on mammography, an association between high levels of sonographic GTC, defined as the percent of glandular tissue within fibroglandular tissue, and an increased risk of breast cancer was demonstrated in a retrospective single-center study of 8483 Korean women. The purpose of this international multicenter study is to prospectively validate whether sonographic GTC is associated with subsequent breast cancer risk and whether it can provide additional information beyond established risk factors. In this study, investigators will enroll 16164 women with dense breasts (BI-RADS density categories C and D on mammography) undergoing screening breast US using either an automated or handheld device. GTC will be assessed qualitatively as minimal, mild, moderate, or marked at the time of US interpretation and will be dichotomized into low (minimal or mild) versus high (moderate or marked). The primary outcome is a pathologic diagnosis of breast cancer, including invasive cancer and ductal carcinoma in situ (DCIS). Women are observed from 3 months after date of GTC assessment to breast cancer diagnosis or censoring as a result of death or end date of complete cancer capture. Covariate information will be obtained from self-report at the time of breast US examination and includes age, race/ethnicity, menopausal status, first-degree family history of breast cancer, breast density, history of benign breast biopsy, BMI, age at first live birth, and hormone replacement therapy (HRT) usage. The 5-year cumulative incidence of breast cancer by level of sonographic GTC will be compared based on marginal standardization with the predicted risk summed to a weighted risk according to the observed covariate distribution in the study population. The association of sonographic GTC with breast cancer risk will be estimated by using the Fine-Gray subdistribution hazards model to account for the competing risk of death. In addition, investigators will compare the discriminatory accuracy of the breast cancer surveillance consortium (BCSC) 5-year risk score and the BCSC model integrated with sonographic GTC.

Study Timeline

• Study First Submitted: 2022-07-12
• Study First Submitted QC: 2022-07-12
• Study First Posted: 2022-07-15
• Study Start: 2022-11-01
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-31
• Last Update Posted: 2024-06-04
• Primary Completion: 2026-03-30
• Study Completion: 2031-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 16164

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incident breast cancer within 3 months to 7 years after the assessment of sonographic GTC	from 3 months to 7 years after the GTC assessment	The 5-year cumulative incidence of breast cancer and hazard ratio by level of sonographic GTC using standardized risk

Secondary Outcome Measures

Name	Time	Method
Correlation of sonographic GTC with breast cancer according to the breast US device	from 3 months to 7 years after the GTC assessment	Correlation of sonographic GTC with breast cancer according to the breast US device (hand-held vs. automated)
Breast US diagnostic performance according to sonographic GTC	from the examination till 1 year after the GTC assessment	Sensitivity, specificity, positive predictive value
Correlation of sonographic GTC with risk according to tumor type	from 3 months to 7 years after the GTC assessment	Correlation of sonographic GTC with risk according to tumor type (DCIS vs. invasive cancer)
The expected-to-observed (E/O) number of cancer diagnoses and concordance index (discriminatory accuracy)	from 3 months to 7 years after the GTC assessment	The expected-to-observed (E/O) number of cancer diagnoses and concordance index (discriminatory accuracy) for the BCSC model (5-year risk score) and BCSC model integrated with sonographic GTC

Trial Locations

Locations (1)

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of