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

July 19, 2023 updated by: Atossa Therapeutics, Inc.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Despite the lack of anatomical clarity in the literature, Tibor Tot has postulated that breast cancer and DCIS are a lobar disease as the simultaneously or asynchronously appearing, often multiple in situ tumor foci are localized within a single "sick" lobe. This theory has some resonance in the molecular studies that have been done in the breast demonstrating that there are large "patches" of clonality even in normal breast tissue. Most of this work was based on microdissection, however, and assumes that adjacent duct profiles belong to the same lobe. In fact both Cooper and Going have shown intertwining of arborizing ducts from different independent lobes. This sets the stage for errors of interpretation in micro-dissected tissue.

Ductal lavage allows the cannulation and lavage of individual ducts and collection of 1,000- over 10,000 exfoliated cells that can be studied for molecular and genetic changes. Ductoscopy adds the ability to confirm that the duct has not been perforated and to brush the lining of the duct to increase cell yield. Real-time ultrasound can be used to confirm the ductal anatomy. With the combination of these minimally invasive techniques it is now possible to collect the cells needed to apply new genetic techniques and investigate the genome of the ductal epithelial cell.

While the methods for obtaining the ductal epithelial cells have been being developed similar advances have been made in whole genome sequencing technology. Knome®, a for-profit company, is now able to analyze ductal cells against blood to identify variants, including single nucleotide polymorphisms (SNP's), short and long insertions and deletions (indels), inversions, translocations, fusion genes and copy number variations (CNVs). Ingenuity Pathway Analysis can identify mRNA networks that can be driving pre-cancerous hyperplasia. Covance Genomics Laboratory (CAL) will perform DNA and RNA extraction, DNA QC and Next-Generation Sequencing on the Illumina platform.

With the combination of these minimally invasive techniques and Next-Generation Sequencing we will be able to test our hypothesis that it is now possible to interrogate the genetic sequence of a single normal duct and to compare it to the sequence in the blood to identify early epithelial mutations. In addition by comparing the sequence of two ducts in one breast we can gain insight into whether each duct is clonal or the whole breast shares the same genetic pattern. And finally, understanding the pathways that are activated in pre-cancerous duct lesions can provide targets for intraductal treatment programs.

Study Type

Observational

Enrollment (Actual)

6

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Santa Monica, California, United States, 90403
        • Dr. Susan Love Research Foundation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

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.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Women with and without breast cancer
Nipple aspirator, ductal lavage microcatheter, blood draw
Device: Nipple aspirator
The subject will undergo nipple aspiration with a suction device designed to elicit fluid from the nipple.
Other Names:
  • Forecyte breast aspirator
Device: Ductal lavage microcatheter
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.
Other Names:
  • FullCYTE Microcatheter
Device: Blood draw
Blood will be drawn and immediately processed for shipping to Covance for WGS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identify early epithelial somatic mutations/indels in precancerous breast ducts by comparing genetic DNA sequences from cells obtained from venous blood and ductal lavage
Time Frame: At six months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
RNA Sequencing on the Illumina Next Generation Sequencing Platform to identify mRNA hyperplasia or precancerous driver pathways
Time Frame: At six months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Atossa Therapeutics, Inc.

Collaborators

Covance
Illumina, Inc.

Investigators

  • Principal Investigator: Dr. Susan Love, MD, The Dr. Susan Love Research Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2011

Primary Completion (Actual)

September 1, 2011

Study Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

April 15, 2014

First Submitted That Met QC Criteria

April 22, 2014

First Posted (Estimated)

April 24, 2014

Study Record Updates

Last Update Posted (Actual)

July 20, 2023

Last Update Submitted That Met QC Criteria

July 19, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • L-503

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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