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

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.

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.