SEMA4C as a Relapse Biomarker in Breast Cancer

Breast cancer remains the most common cancer in women worldwide. Semaphorin4C (SEMA4C) has previously been identified as a highly expressed protein by breast cancer-associated lymphatic endothelial cells (LECs). The objective of this study is to investigate SEMA4C's potential role as an early relapse biomarker in breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: SEMA4C high value follow-up group; Other: SEMA4C low value follow-up group

Detailed Description

Breast cancer remains the most common cancer in women worldwide, with approximately 1.68 million new cases, and 0.52 million deaths, annually. Meanwhile the incidence of breast cancer continues to increase. Although regular clinical examination, mammography, ultrasonography, and magnetic resonance imaging can detect some recurrence patients, the lack of robust biomarkers for monitoring of anti-tumor therapies and detection of recurrence reduce the treatment effectiveness of current strategies for breast cancer.

Semaphorin4C (SEMA4C) has been previously identified as a highly expressed protein by breast cancer-associated lymphatic endothelial cells (LECs) using in situ laser capture microdissection of lymphatic vessels, followed by cDNA microarray analysis. Moreover, membrane-bound SEMA4C is cleaved by matrix metalloproteinase (MMPs) to release a soluble form of this protein. The study is undertaken to explore SEMA4C's potential role as an early relapse biomarker in breast cancer.

• Study Type: Observational
• Enrollment (Anticipated): 4200

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Participants including patients with breast cancer. All cases were confirmed histopathologically according to the WHO Classification of Tumors.

Description

Inclusion Criteria:

• Have histologically confirmed new diagnosis of breast cancer according to biopsy or surgery

Exclusion Criteria:

• Patients who are not mentally capable of giving written informed consent
• Serum samples doesn't qualified
• Patients who refuse follow-up on their conditions
• Patients with prior cancer history
• Patients with a diagnosis of other severe acute or chronic medical may increase the risk associated with study participation or may interfere with the interpretation of the study results and, in the judgement of the Investigator, would make the patient inappropriate for enrollment in this study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SEMA4C high value follow-up group; Postoperative SEMA4C value is higher than 5.00 ng/ml.	Other: SEMA4C high value follow-up group; Serum samples will be collected every 3 months for the first year after surgery and then every 6 months to first progression defined as death or recurrence of the breast cancer or until 5 years since last patient in, whichever occurs first. Imaging examination and biopsy or surgery if necessary are recommended for patients with elevated SEMA4C. Serum SEMA4C levels will be tested in single center in order to decrease bias and be measured using a double antibody sandwich ELISA method using in-house SEMA4C detection kits.
SEMA4C low value follow-up group; Postoperative SEMA4C value is lower than 5.00 ng/ml.	Other: SEMA4C low value follow-up group; Serum samples will be collected every 3 months for the first year after surgery and then every 6 months to first progression defined as death or recurrence of the breast cancer or until 5 years since last patient in, whichever occurs first. Imaging examination and biopsy or surgery if necessary are recommended for patients with elevated SEMA4C. Serum SEMA4C levels will be tested in single center in order to decrease bias and be measured using a double antibody sandwich ELISA method using in-house SEMA4C detection kits.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diagnostic accuracy (sensitivity, specificity, positive predictive value, negative predictive value) of SEMA4C in predicting recurrence of breast cancer	Analyze the sensitivity, specificity, positive predictive value, negative predictive value, accuracy of SEMA4C in predicting recurrence of breast cancer	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Free Survival	Disease Free Survival (DFS) can be determined according to clinical practice based on any of the following: applicable imaging technique, biopsy and surgery.	5 years

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Qilu Hospital of Shandong University; Hubei Cancer Hospital; The First People's Hospital of Jingzhou; Wuhan Central Hospital; Xiangyang Central Hospital

Publications and helpful links

General Publications

• Wei JC, Yang J, Liu D, Wu MF, Qiao L, Wang JN, Ma QF, Zeng Z, Ye SM, Guo ES, Jiang XF, You LY, Chen Y, Zhou L, Huang XY, Zhu T, Meng L, Zhou JF, Feng ZH, Ma D, Gao QL. Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C. Clin Cancer Res. 2017 Jan 1;23(1):214-224. doi: 10.1158/1078-0432.CCR-16-0741. Epub 2016 Jul 8.
• Gurrapu S, Pupo E, Franzolin G, Lanzetti L, Tamagnone L. Sema4C/PlexinB2 signaling controls breast cancer cell growth, hormonal dependence and tumorigenic potential. Cell Death Differ. 2018 Jul;25(7):1259-1275. doi: 10.1038/s41418-018-0097-4. Epub 2018 Mar 19.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2026

Study Registration Dates

• First Submitted: September 3, 2018
• First Submitted That Met QC Criteria: September 5, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Actual): October 7, 2021
• Last Update Submitted That Met QC Criteria: October 6, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2018-TJ-BCP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No