Long-term Safety of Nipple Sparing Mastectomy in Women With High Penetrance Breast Cancer Susceptibility Genes in Breast Cancer

NCT ID: NCT06888388

Last Updated: 2025-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

4700 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-02-01

Study Completion Date

2028-02-01

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Cancer Surgery

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Risk Reducing Mastectomy

Nipple Sparing Mastectomy (NSM)

Intervention Type PROCEDURE

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)

Intervention Type PROCEDURE

Skin sparing mastectomy (SSM) is a procedure that removes the nipple and areola complex along with all visible macroscopic breast glandular tissue.

Total (Simple) Mastectomy

Intervention Type PROCEDURE

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.

Active surveillance

No interventions assigned to this group

Interventions

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Nipple Sparing Mastectomy (NSM)

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.

Intervention Type PROCEDURE

Skin-Sparing Mastectomy (SSM)

Skin sparing mastectomy (SSM) is a procedure that removes the nipple and areola complex along with all visible macroscopic breast glandular tissue.

Intervention Type PROCEDURE

Total (Simple) Mastectomy

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.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research Society

OTHER

Sponsor Role collaborator

Quebec Breast Cancer Foundation

OTHER

Sponsor Role collaborator

Sir Mortimer B. Davis - Jewish General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Stephanie Wong

Assistant Professor of Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

Brigham and Women's Hospital - Dana-Farber Brigham Cancer Center

Boston, Massachusetts, United States

Site Status NOT_YET_RECRUITING

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

Site Status NOT_YET_RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

University of Melbourne, Peter MacCallum Cancer Center

Melbourne, , Australia

Site Status NOT_YET_RECRUITING

Ziekenhuis Aan de Stroom

Antwerp, , Belgium

Site Status ACTIVE_NOT_RECRUITING

University of Calgary

Calgary, Alberta, Canada

Site Status RECRUITING

Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status RECRUITING

Women's College Hospital, University of Toronto

Toronto, Ontario, Canada

Site Status NOT_YET_RECRUITING

Jewish General Hospital

Montreal, Quebec, Canada

Site Status RECRUITING

CHU de Quebec Université laval

Québec, Quebec, Canada

Site Status RECRUITING

Champalimaud Foundation, University of Lisbon

Lisbon, , Portugal

Site Status NOT_YET_RECRUITING

Countries

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United States Australia Belgium Canada Portugal

Central Contacts

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Stephanie Wong, MD

Role: CONTACT

5143408222

Sarah Sabboobeh, MSc

Role: CONTACT

5143408222

Facility Contacts

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Jacqueline Moses

Role: primary

Julie Vincuilla

Role: primary

Tari King, MD

Role: backup

Giacomo Montagna, MD

Role: primary

Catherine Wolfe

Role: primary

Magdalena Sejka, MD

Role: primary

Anita Skandarajah, MD

Role: backup

Susan Isherwood, PhD

Role: primary

Elena Parvez, MD

Role: primary

Julie Takata

Role: primary

David Lim, MD

Role: backup

Sarah Sabboobeh, MSc

Role: primary

5143408222

Stephanie Wong, MD

Role: backup

Christian Laflamme, PhD

Role: primary

Maria Joao Cardoso, MD

Role: primary

Other Identifiers

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MP-05-2025-4291 (MP)

Identifier Type: -

Identifier Source: org_study_id

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