The Breast Duct: Pilot Study of Genomic Sequencing of Exfoliated Ductal Cells Obtained Through Endoscopy and Lavage

NCT02121873 | Completed

• 1 other identifier: L-503
• Study Type: observational
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to determine whether we can use minimally invasive techniques to gain access to exfoliated ductal epithelial cells for whole genome sequencing.

1. 1.To examine women with nipple aspiration, ductoscopy and ductal lavage and collect exfoliated cells from two ducts per woman.
2. 2.To collect a blood sample at the time of the examination in order to obtain the woman's baseline genomic sequence.
3. 3.De-identified samples will then have DNA and RNA extracted and whole genome sequencing and transcriptome analysis performed by Covance and Illumina.
4. 4.Comparisons will be made within a breast (two ducts) and between the duct and blood as well as between women.

Conditions

Breast Cancer; Preneoplastic Conditions; Ductal Carcinoma in Situ

Keywords

breast cancer, nipple aspirate, ductal lavage, hyperplasia

Outcome Measures

Primary Outcomes (1)

• Identify early epithelial somatic mutations/indels in precancerous breast ducts by comparing genetic DNA sequences from cells obtained from venous blood and ductal lavage

  Extract high-quality DNA and RNA from human whole blood and ductal lavage (DL) samples. Assess QC and Quantitation of extracted RNA and DNA samples. Assess QC and Quantitation of libraries generated by CGL for Whole Genome DNA-seq and RNA sequencing assays. Sequence prepared libraries using the Illumina Next Generation Sequencing platform.

  At six months

Secondary Outcomes (1)

• RNA Sequencing on the Illumina Next Generation Sequencing Platform to identify mRNA hyperplasia or precancerous driver pathways

  At six months

Study Arms (1)

Women with and without breast cancer

Nipple aspirator, ductal lavage microcatheter, blood draw

Device: Nipple aspirator; Device: Ductal lavage microcatheter; Device: Blood draw

Interventions

Nipple aspirator DEVICE

The subject will undergo nipple aspiration with a suction device designed to elicit fluid from the nipple.

Also known as: Forecyte breast aspirator

Women with and without breast cancer

Ductal lavage microcatheter DEVICE

Upon completion of the nipple aspiration procedure, subjects will undergo a nipple block with local anesthesia. The duct will be lavaged with the ductal lavage microcatheter. Samples will be immediately processed for shipping to Covance for WGS. Subjects will be contacted 24 hours and again 2 weeks after the procedure to collect any untoward effects of participating in the study.

Also known as: FullCYTE Microcatheter

Women with and without breast cancer

Blood draw DEVICE

Blood will be drawn and immediately processed for shipping to Covance for WGS.

Women with and without breast cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women will be recruited from our local pool of volunteers who have participated in previous studies of ductal lavage and/or ductoscopy at the Foundation.

You may qualify if:

• Be female
• Have at least one intact nipple
• If over 50, have had a normal mammogram within 12 months prior to the enrollment date
• Have a normal physical examination of the breast to be studied within 12 months prior to the enrollment date
• Be \> 18 years of age
• Sign the informed consent form

You may not qualify if:

• Be currently pregnant or pregnant within the last 12 months
• Be currently lactating or lactated within the last 12 months
• Have received chemotherapy in the last 12 months
• Have had an abnormal mammogram within the last year
• Have had any subareolar or other surgery (papilloma resections, biopsies or fine needle aspirations) within 2 centimeters of the nipple (biopsies and fine needle aspirations \>2 centimeters from the nipple are acceptable)
• Have active infections or inflammation in a breast to be studied
• Have a known allergy to lidocaine
• Be unwilling to sign informed consent

Sponsors & Collaborators

• Atossa Therapeutics, Inc.: lead
• Covance: collaborator
• Illumina, Inc.: collaborator

Study Sites (1)

Dr. Susan Love Research Foundation

Santa Monica, California, 90403, United States

Location

Related Publications (5)

• Mahoney ME, Gordon EJ, Rao JY, Jin Y, Hylton N, Love SM. Intraductal therapy of ductal carcinoma in situ: a presurgery study. Clin Breast Cancer. 2013 Aug;13(4):280-6. doi: 10.1016/j.clbc.2013.02.002. Epub 2013 May 9.

  PMID: 23664819 BACKGROUND

• Love SM, Zhang W, Gordon EJ, Rao J, Yang H, Li J, Zhang B, Wang X, Chen G, Zhang B. A feasibility study of the intraductal administration of chemotherapy. Cancer Prev Res (Phila). 2013 Jan;6(1):51-8. doi: 10.1158/1940-6207.CAPR-12-0228. Epub 2012 Nov 20.

  PMID: 23169924 BACKGROUND

• Mannello F, Ligi D. Resolving breast cancer heterogeneity by searching reliable protein cancer biomarkers in the breast fluid secretome. BMC Cancer. 2013 Jul 12;13:344. doi: 10.1186/1471-2407-13-344.

  PMID: 23849048 BACKGROUND

• Ma CX, Ellis MJ. The Cancer Genome Atlas: clinical applications for breast cancer. Oncology (Williston Park). 2013 Dec;27(12):1263-9, 1274-9.

  PMID: 24624545 BACKGROUND

• Kaur H, Mao S, Shah S, Gorski DH, Krawetz SA, Sloane BF, Mattingly RR. Next-generation sequencing: a powerful tool for the discovery of molecular markers in breast ductal carcinoma in situ. Expert Rev Mol Diagn. 2013 Mar;13(2):151-65. doi: 10.1586/erm.13.4.

  PMID: 23477556 BACKGROUND

Related Links

• Dr. Susan Love Research Foundation

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, nipple aspirate fluid, ductal lavage fluid

MeSH Terms

Conditions

Breast Neoplasms; Precancerous Conditions; Carcinoma, Intraductal, Noninfiltrating; Hyperplasia

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Dr. Susan Love, MD

  The Dr. Susan Love Research Foundation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: April 24, 2014
• Study Start: July 1, 2011
• Primary Completion: September 1, 2011
• Study Completion: August 1, 2012
• Last Updated: July 20, 2023

Record last verified: 2023-07

Locations

US (1)