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NCT06888388Recruiting

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

Sir Mortimer B. Davis - Jewish General Hospital

Start Date

2/1/2025

Completion Date

2/1/2028

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.

Eligibility Criteria

Age Range: 18 years to 90 years

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.

Interventions

PROCEDURE

Nipple Sparing Mastectomy (NSM)

PROCEDURE

Skin-Sparing Mastectomy (SSM)

PROCEDURE

Total (Simple) Mastectomy

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Conditions

Breast Cancer Surgery

Locations

Yale University

New Haven, Connecticut 06510

United States

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

Boston, Massachusetts 02115

United States

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York 10065

United States

University of Pennsylvania

Philadelphia, Pennsylvania 19104-6205

United States

University of Melbourne, Peter MacCallum Cancer Center

Melbourne,

Australia

Ziekenhuis Aan de Stroom

Antwerp, 2030

Belgium

University of Calgary

Calgary, Alberta T2N 4N1

Canada

Hamilton Health Sciences

Hamilton, Ontario L8L 2X2

Canada

Women's College Hospital, University of Toronto

Toronto, Ontario

Canada

Jewish General Hospital

Montreal, Quebec H3T1E2

Canada

CHU de Quebec Université laval

Québec, Quebec G1S 4L8

Canada

Champalimaud Foundation, University of Lisbon

Lisbon,

Portugal