Breast CancerNCT02121873
The Breast Duct: Pilot Study of Genomic Sequencing of Exfoliated Ductal Cells Obtained Through Endoscopy and Lavage
An observational study of Breast Cancer and Preneoplastic Conditions, run by Atossa Therapeutics, Inc. at 1 site in United States.
Trial 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. To examine women with nipple aspiration, ductoscopy and ductal lavage and collect exfoliated cells from two ducts per woman. 2. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer, Preneoplastic Conditions, Ductal Carcinoma in Situ
- What is being tested?
- Nipple aspirator, Ductal lavage microcatheter and Blood draw
- Type of treatment
- Medical device
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Aug 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Dr. Susan Love Research Foundation
Santa Monica, California, 90403
About this study
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.
- To examine women with nipple aspiration, ductoscopy and ductal lavage and collect exfoliated cells from two ducts per woman.
- To collect a blood sample at the time of the examination in order to obtain the woman's baseline genomic sequence.
- De-identified samples will then have DNA and RNA extracted and whole genome sequencing and transcriptome analysis performed by Covance and Illumina.
- Comparisons will be made within a breast (two ducts) and between the duct and blood as well as between women.
Read the 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.
- Being tested
- Nipple aspirator, Ductal lavage microcatheter, Blood draw
- Keywords
- breast cancer, nipple aspirate, ductal lavage, hyperplasia
- Medical subject headings
- Breast Neoplasms, Precancerous Conditions, Carcinoma, Intraductal, Noninfiltrating, Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nipple aspiratorDevice
Also called Forecyte breast aspirator
The subject will undergo nipple aspiration with a suction device designed to elicit fluid from the nipple.
Ductal lavage microcatheterDevice
Also called FullCYTE 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.
Blood drawDevice
Blood will be drawn and immediately processed for shipping to Covance for WGS.
| Study group | Role | What they receive |
|---|---|---|
| Women with and without breast cancer | Nipple aspirator, ductal lavage microcatheter, blood draw Receives: Device: Nipple aspirator; Device: Ductal lavage microcatheter; Device: Blood draw |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At six months
Secondary outcomes (1)
RNA Sequencing on the Illumina Next Generation Sequencing Platform to identify mRNA hyperplasia or precancerous driver pathways
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.
Measured: At six months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2014 (estimated)
- Study startJul 2011
- Primary completionSep 2011
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Atossa Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Covance, Illumina, Inc.
- Responsible party
- Sponsor
- Investigators
- Dr. Susan Love, MD, Principal investigator, The Dr. Susan Love Research Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02121873
- Sponsor's protocol ID
- L-503
- Status last verified
- Jul 2023
- First submitted
- 15 Apr 2014
- Last updated
- 20 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 23664819Love 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.
PubMed 23169924Mannello 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.
PubMed 23849048Ma CX, Ellis MJ. The Cancer Genome Atlas: clinical applications for breast cancer. Oncology (Williston Park). 2013 Dec;27(12):1263-9, 1274-9.
PubMed 24624545Kaur 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.
PubMed 23477556
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Breast Duct: Pilot Study of Genomic Sequencing of Exfoliated Ductal Cells Obtained Through Endoscopy and Lavage
- ClinicalTrials.gov ID
- NCT02121873
- Acronym / sponsor ID
- L-503
- Keywords
- breast cancer, nipple aspirate, ductal lavage, hyperplasia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Atossa Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Covance, Illumina, Inc.
- Study start
- Jul 2011
- Primary completion
- Sep 2011 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 24 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- To examine women with nipple aspiration, ductoscopy and ductal lavage and collect exfoliated cells from two ducts per woman.
- To collect a blood sample at the time of the examination in order to obtain the woman's baseline genomic sequence.
- De-identified samples will then have DNA and RNA extracted and whole genome sequencing and transcriptome analysis performed by Covance and Illumina.
- Comparisons will be made within a breast (two ducts) and between the duct and blood as well as between women.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Women with and without breast cancer | – | Device: Nipple aspirator, Device: Ductal lavage microcatheter, Device: Blood drawNipple aspirator, ductal lavage microcatheter, blood draw |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nipple aspiratorAlso: Forecyte breast aspiratorThe subject will undergo nipple aspiration with a suction device designed to elicit fluid from the nipple. | Device | Women with and without breast cancer |
| Ductal lavage microcatheterAlso: FullCYTE MicrocatheterUpon 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. | Device | Women with and without breast cancer |
| Blood drawBlood will be drawn and immediately processed for shipping to Covance for WGS. | Device | Women with and without breast cancer |
Primary outcome
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.
1 secondary outcome
RNA Sequencing on the Illumina Next Generation Sequencing Platform to identify mRNA hyperplasia or precancerous driver pathways
Time frame: At six months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2023.
- Background: PubMed 23664819Mahoney 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.
- Background: PubMed 23169924Love 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.
- Background: PubMed 23849048Mannello 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.
- Background: PubMed 24624545Ma CX, Ellis MJ. The Cancer Genome Atlas: clinical applications for breast cancer. Oncology (Williston Park). 2013 Dec;27(12):1263-9, 1274-9.
- Background: PubMed 23477556Kaur 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dr. Susan Love, MD principal investigator
The Dr. Susan Love Research Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer and Preneoplastic Conditions, run by Atossa Therapeutics, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02121873, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.