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

Breast Cancer Clinical Trial

Official title:

Association of Sonographic Glandular Tissue Component With Breast Cancer Risk Among Women With Dense Breasts: A Prospective, Multinational Validation Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05460975
• Other study ID #: Breast Cancer Risk
• Status: Recruiting
• Start date: November 1, 2022
• Est. completion date: December 30, 2031

Study information

• Verified date: May 2024
• Source: Seoul National University Hospital
• Contact: Woo Kyung Moon, MD, PhD
• Phone: +82220722584
• Email: moonwk1963[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16164
• Est. completion date: December 30, 2031
• Est. primary completion date: March 30, 2026
• Gender: Female
• Age group: 40 Years to 69 Years

Eligibility

Inclusion Criteria

1. be = 40 and <70 years old at time of US

2. No history of previous breast cancer including DCIS

3. have dense breasts (BI-RADS category C and D on mammography performed within 12 months of breast US) and negative/benign BI-RADS assessment categories on mammography (BI-RADS 1, 2)

4. undergoing screening breast US using either automated or handheld device

Exclusion Criteria

1. history of bilateral prophylactic mastectomy

2. history of bilateral foreign body injection

3. history of bilateral breast implants

4. history of bilateral breast reduction surgery or surgical excision

5. currently pregnant or breast feeding in the preceding 6 months

6. Known distant metastasis from other primary cancer

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Screening

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (3)

Acciavatti RJ, Lee SH, Reig B, Moy L, Conant EF, Kontos D, Moon WK. Beyond Breast Density: Risk Measures for Breast Cancer in Multiple Imaging Modalities. Radiology. 2023 Mar;306(3):e222575. doi: 10.1148/radiol.222575. Epub 2023 Feb 7. — View Citation

Lee SH, Moon WK. Glandular Tissue Component on Breast Ultrasound in Dense Breasts: A New Imaging Biomarker for Breast Cancer Risk. Korean J Radiol. 2022 Jun;23(6):574-580. doi: 10.3348/kjr.2022.0099. No abstract available. — View Citation

Lee SH, Ryu HS, Jang MJ, Yi A, Ha SM, Kim SY, Chang JM, Cho N, Moon WK. Glandular Tissue Component and Breast Cancer Risk in Mammographically Dense Breasts at Screening Breast US. Radiology. 2021 Oct;301(1):57-65. doi: 10.1148/radiol.2021210367. Epub 2021 Jul 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incident breast cancer within 3 months to 7 years after the assessment of sonographic GTC	The 5-year cumulative incidence of breast cancer and hazard ratio by level of sonographic GTC using standardized risk	from 3 months to 7 years after the GTC assessment
Secondary	Correlation of sonographic GTC with risk according to tumor type	Correlation of sonographic GTC with risk according to tumor type (DCIS vs. invasive cancer)	from 3 months to 7 years after the GTC assessment
Secondary	Correlation of sonographic GTC with breast cancer according to the breast US device	Correlation of sonographic GTC with breast cancer according to the breast US device (hand-held vs. automated)	from 3 months to 7 years after the GTC assessment
Secondary	The expected-to-observed (E/O) number of cancer diagnoses and concordance index (discriminatory accuracy)	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	from 3 months to 7 years after the GTC assessment
Secondary	Breast US diagnostic performance according to sonographic GTC	Sensitivity, specificity, positive predictive value	from the examination till 1 year after the GTC assessment