RecruitingNCT06888388

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

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


Sponsor

Sir Mortimer B. Davis - Jewish General Hospital

Enrollment

4,700 participants

Start Date

Feb 1, 2025

Study Type

OBSERVATIONAL

Conditions

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

Sex: FEMALEMin Age: 18 YearsMax Age: 90 Years

Inclusion Criteria3

  • 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 Criteria4

  • 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

PROCEDURENipple 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.

PROCEDURESkin-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.

PROCEDURETotal (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.


Locations(12)

Yale University

New Haven, Connecticut, United States

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

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center (MSKCC)

New York, New York, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Melbourne, Peter MacCallum Cancer Center

Melbourne, Australia

Ziekenhuis Aan de Stroom

Antwerp, Belgium

University of Calgary

Calgary, Alberta, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

Women's College Hospital, University of Toronto

Toronto, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

CHU de Quebec Université laval

Québec, Quebec, Canada

Champalimaud Foundation, University of Lisbon

Lisbon, Portugal

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NCT06888388


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