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

NCT06888388 | Recruiting

• 1 other identifier: MP-05-2025-4291 (MP)
• Study Type: observational
• Target: 4,700
• Locations: 5 countries
• Sites: 12

Brief 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. 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

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

Outcome Measures

Primary Outcomes (1)

• 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.

  10 years

Secondary Outcomes (5)

• Incidence of RRM

  10 years

• Incidence of post-operative complications

  10 years

• Incidence of pathologic outcomes following NSM

  10 years

• Number of participants using endocrine prevention

  10 years

• Number of participants who have undergone pre-mastectomy imaging and post-mastectomy surveillance

  10 years

Study Arms (2)

Risk Reducing Mastectomy

Procedure: Nipple Sparing Mastectomy (NSM); Procedure: Skin-Sparing Mastectomy (SSM); Procedure: Total (Simple) Mastectomy

Active surveillance

Interventions

Nipple Sparing Mastectomy (NSM) 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.

Risk Reducing Mastectomy

Skin-Sparing Mastectomy (SSM) PROCEDURE

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

Risk Reducing Mastectomy

Total (Simple) Mastectomy 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.

Risk Reducing Mastectomy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sir Mortimer B. Davis - Jewish General Hospital: lead
• Cancer Research Society: collaborator
• Quebec Breast Cancer Foundation: collaborator

Study Sites (12)

Yale University

New Haven, Connecticut, 06510, United States

RECRUITING

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

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, 10065, United States

NOT YET RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104-6205, United States

RECRUITING

University of Melbourne, Peter MacCallum Cancer Center

Melbourne, Australia

NOT YET RECRUITING

Ziekenhuis Aan de Stroom

Antwerp, 2030, Belgium

ACTIVE NOT RECRUITING

University of Calgary

Calgary, Alberta, T2N 4N1, Canada

RECRUITING

Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

RECRUITING

Women's College Hospital, University of Toronto

Toronto, Ontario, Canada

NOT YET RECRUITING

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

RECRUITING

CHU de Quebec Université laval

Québec, Quebec, G1S 4L8, Canada

RECRUITING

Champalimaud Foundation, University of Lisbon

Lisbon, Portugal

NOT YET RECRUITING

MeSH Terms

Conditions

Li-Fraumeni Syndrome; Hamartoma Syndrome, Multiple

Interventions

Mastectomy, Subcutaneous; Mastectomy

Condition Hierarchy (Ancestors)

Neoplastic Syndromes, Hereditary; Neoplasms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Hamartoma; Neoplasms, Multiple Primary

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative

Central Study Contacts

Stephanie Wong, MD

CONTACT

5143408222; sm.wong@mcgill.ca

Sarah Sabboobeh, MSc

CONTACT

5143408222; sarah.sabboobe@ladydavis.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Surgery

Study Record Dates

• First Submitted: March 15, 2025
• First Posted: March 21, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); AU (1); BE (1); CA (5); PT (1)