Breast Cancer SurgeryNSMNCT06888388
Long-term Safety of Nipple Sparing Mastectomy in Women With High Penetrance Breast Cancer Susceptibility Genes in Breast Cancer
An observational study of Breast Cancer Surgery, run by Sir Mortimer B. Davis - Jewish General Hospital at 16 sites in 8 countries.
Trial summary
Patients with a germline pathogenic variant (GPV) in high-penetrance breast cancer susceptibility genes who are considering risk reducing mastectomy (RRM) often strongly desire to keep their nipple areola complex but inquire as to whether it is safe to do so. Read more about this study
- Who is it for?
- Ages 18 to 90 years, women only
- Conditions the study is for
- Breast Cancer Surgery
- What is being tested?
- Nipple Sparing Mastectomy (NSM), Skin-Sparing Mastectomy (SSM) and Total (Simple) Mastectomy
- Type of treatment
- Surgery or procedure
- How many people
- 4,700 participants
- Where
- 16 sitesin 8 countries
- Study dates
- 1 Feb 2025to 1 Feb 2028
- Phase
- Observational
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 to 90 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Female patients aged 18-years or older with a confirmed GPV in BRCA1, BRCA2, PALB2, TP53, CDH1 or PTEN identified on pre-symptomatic genetic testing performed between January 1, 1994-June 30, 2024
Who may be able to join
- Assigned female sex at birth
- Age 18 years or older
- Confirmed GPV in BRCA1, BRCA2, PALB2, TP53, CDH1 or PTEN identified on pre-symptomatic genetic testing
Who cannot join
- History of breast cancer prior to genetic testing
- History of ovarian cancer prior to genetic testing
- History of bilateral mastectomy performed prior to genetic testing
- Presence of a variant of uncertain significance (VUS) in the absence of another GPV in BRCA1, BRCA2, PALB2, TP53, CDH1 or PTEN.
Trial locations and contacts
16 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
16 sites in 8 countries
United States5 sites, 5 recruiting
- Not yet recruiting
Brigham and Women's Hospital - Dana-Farber Brigham Cancer Center
Boston, Massachusetts, 02115
Julie Vincuilla, jvincuilla@bwh.harvard.edu
Tari King, MD, tking7@bwh.harvard.edu
- Recruiting
Yale University
New Haven, Connecticut, 06510
Jacqueline Moses, jacki.moses@yale.edu
Mehra Golshan, MD
- Not yet recruiting
Memorial Sloan Kettering Cancer Center (MSKCC)
New York, New York, 10065
Giacomo Montagna, MD, MontagnG@mskcc.org
Giacomo Montagna, MD
- Recruiting
University of Pennsylvania
Philadelphia, Pennsylvania, 19104-6205
Catherine Wolfe, catherine.wolfe@pennmedicine.upenn.edu
Susan Domchek, MD
- Not yet recruiting
University of Rochester, Wilmot Cancer Institute
Rochester, New York, 14642
Anna Weiss, MD, Anna_Weiss@URMC.Rochester.edu
Canada5 sites, 5 recruiting
- Recruiting
University of Calgary
Calgary, Alberta, T2N 4N1
Susan Isherwood, PhD, Susan.Isherwood@albertahealthservices.ca
Alison Laws, MD
- Recruiting
Hamilton Health Sciences
Hamilton, Ontario, L8L 2X2
Elena Parvez, MD, parveze@mcmaster.ca
Elena Parvez, MD
- Recruiting
Jewish General Hospital
Montreal, Quebec, H3T1E2
Sarah Sabboobeh, MSc, 5143408222, sarah.sabboobeh@ladydavis.ca
Stephanie Wong, MD, sm.wong@mcgill.ca
- Recruiting
CHU de Quebec Université laval
Québec, Quebec, G1S 4L8
Christian Laflamme, PhD, Christian.Laflamme@crchudequebec.ulaval.ca
Gabrielle Bergerone-Giguere, MD
- Not yet recruiting
Women's College Hospital, University of Toronto
Toronto, Ontario
Julie Takata, Julie.Takata@wchospital.ca
David Lim, MD, David.Lim@wchospital.ca
Australia1 site, 1 recruiting
- Not yet recruiting
University of Melbourne, Peter MacCallum Cancer Center
Melbourne
Magdalena Sejka, MD, Magdalena.Sejka@mh.org.au
Anita Skandarajah, MD, Anita.Skandarajah@petermac.org
Japan1 site, 1 recruiting
- Recruiting
Cancer Institute Hospital of JFCR, Tokyo
Tokyo
Takehiko Sakai, MD, takehiko.sakai@jfcr.or.jp
Portugal1 site, 1 recruiting
- Not yet recruiting
Champalimaud Foundation, University of Lisbon
Lisbon
Maria Joao Cardoso, MD, maria.joao.cardoso@fundacaochampalimaud.pt
Maria Joao Cardoso, MD
South Korea1 site, 1 recruiting
- Recruiting
Asan Medical Centre
Seoul
Jisun Kim, MD, jisunkim@amc.seoul.kr
United Kingdom1 site, 1 recruiting
- Recruiting
Belfast Health & Social Care Trust
Belfast
Stuart McIntosh, MD, s.mcintosh@qub.ac.uk
About this study
Official title: Long-term Oncologic Safety of Nipple Sparing Mastectomy in Women With High Penetrance Germline Pathogenic Variants in Breast Cancer Susceptibility Genes
Patients with a germline pathogenic variant (GPV) in high-penetrance breast cancer susceptibility genes who are considering risk reducing mastectomy (RRM) often strongly desire to keep their nipple areola complex but inquire as to whether it is safe to do so. Relative to traditional or skin sparing mastectomy (SSM) techniques, nipple sparing mastectomy (NSM) is associated with improved psychosocial and sexual well-being and is significantly better for body image and reducing feelings of disfigurement.
Despite this, guidelines have yet to endorse the use of NSM over other RRM techniques, stating that more data and longer follow-up are needed to confirm it as a safe and effective strategy in GPV carriers. As NSM was not routinely adopted in high-risk patient populations undergoing RRM before 2010, there has been little data to inform the long-term oncologic safety of NSM. Well-designed studies have reported low to negligible rates of subsequent breast cancer in BRCA1/2 carriers following NSM, but have been limited by short median follow-up of less than 3 years. The current study is designed to confirm, with longer follow-up, prior findings on the oncologic safety of NSM in unaffected BRCA1/2 carriers. The investigators will also expand data to other high-penetrance GPV carriers, including PALB2, CDH1, PTEN, and TP53, for whom there is little-to-no data on outcomes following RRM.
- Conditions
- Breast Cancer Surgery
- Being tested
- Nipple Sparing Mastectomy (NSM), Skin-Sparing Mastectomy (SSM), Total (Simple) Mastectomy
- Keywords
- breast cancer surgery, nipple sparing mastectomy, oncologic safety, Cancer prevention, Breast Cancer Prevention, BRCA, germline pathogenic variant, GPV, Li Fraumeni, Hereditary lobular breast cancer, Cowden syndrome, PALB2
- Medical subject headings
- Li-Fraumeni Syndrome, Hamartoma Syndrome, Multiple
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nipple Sparing Mastectomy (NSM)Procedure or surgery
Nipple sparing mastectomy (NSM) is a surgical procedure which removes all macroscopic breast glandular tissue while retaining the skin as well as the nipple areola complex.
Skin-Sparing Mastectomy (SSM)Procedure or surgery
Skin sparing mastectomy (SSM) is a procedure that removes the nipple and areola complex along with all visible macroscopic breast glandular tissue.
Total (Simple) MastectomyProcedure or surgery
Total (Simple) Mastectomy is a traditional mastectomy approach that removes the breast glandular tissue with a large overlying area of skin including the nipple and areola complex to allow for flat closure.
| Study group | Role | What they receive |
|---|---|---|
| Risk Reducing Mastectomy | Not described Receives: Procedure: Nipple Sparing Mastectomy (NSM); Procedure: Skin-Sparing Mastectomy (SSM); Procedure: Total (Simple) Mastectomy | |
| Active surveillance | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of breast cancer following RRM
The primary outcome of interest is the incidence of breast cancer following RRM, defined as a histologically confirmed diagnosis of in situ or invasive breast cancer present within the nipple/areola, skin, subcutaneous tissue of the chest wall/reconstructed breast, or axillary lymph nodes. Patients with clinically occult invasive breast cancer diagnosed at the time of RRM (ie. on mastectomy pathology) will be excluded from the primary outcome analysis.
Measured: 10 years
Secondary outcomes (5)
Incidence of RRM
To evaluate uptake of RRM versus active surveillance amongst an international cohort of unaffected women with high-penetrance GPVs in BRCA1/2, PALB2, CDH1, PTEN, or TP53
Measured: 10 years
Incidence of post-operative complications
To evaluate post-operative complications and supplemental surgery following NSM, SSM, and total mastectomy in those undergoing RRM
Measured: 10 years
Incidence of pathologic outcomes following NSM
To evaluate pathologic outcomes following RRM, including the presence of high-risk lesions or occult in situ and/or invasive malignancy
Measured: 10 years
Number of participants using endocrine prevention
To explore the use of endocrine prevention in unaffected women with high-penetrance GPVs in BRCA1/2, PALB2, CDH1, PTEN, or TP53 who elect to undergo active surveillance
Measured: 10 years
Number of participants who have undergone pre-mastectomy imaging and post-mastectomy surveillance
To assess practices in pre-mastectomy imaging and post-mastectomy surveillance, including the number of participants who underwent preoperative MRI and mammography as well as post-mastectomy surveillance, including MRI, ultrasound and chest wall examination.
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2025
- Study start1 Feb 2025
- Primary completion1 Feb 2027 (estimated)
- Study completion1 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Cancer SurgeryStudies 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
- Retrospective
- Enrolment
- 4,700 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sir Mortimer B. Davis - Jewish General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research Society, Quebec Breast Cancer Foundation
- Responsible party
- Principal investigator, Stephanie Wong, Sir Mortimer B. Davis - Jewish General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06888388
- Sponsor's protocol ID
- MP-05-2025-4291 (MP)
- Acronym
- NSM
- Status last verified
- Aug 2026
- First submitted
- 15 Mar 2025
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No