Clinical trial NCT06888388: Long-term Safety of Nipple Sparing Mastectomy in Women With GPV in Breast Cancer
Official title: Long-term Oncologic Safety of Nipple Sparing Mastectomy in Women With High Penetrance Germline Pathogenic Variants in Breast Cancer Susceptibility Genes
Study type: OBSERVATIONAL
Overall status: RECRUITING
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
Lead sponsor: Sir Mortimer B. Davis - Jewish General Hospital
Sponsor class: OTHER
Collaborators: name: Cancer Research Society
name: Quebec Breast Cancer Foundation
First posted: 2025-03-21
Enrollment: 4700
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of breast cancer following RRM
timeFrame: 10 years
Secondary outcomes:
measure: Incidence of RRM
timeFrame: 10 years
measure: Incidence of post-operative complications
timeFrame: 10 years
measure: Incidence of pathologic outcomes following NSM
timeFrame: 10 years
measure: Number of participants using endocrine prevention
timeFrame: 10 years
measure: Number of participants who have undergone pre-mastectomy imaging and post-mastectomy surveillance
timeFrame: 10 years
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Boston
country: United States
facility: Brigham and Women's Hospital - Dana-Farber Brigham Cancer Center
state: Massachusetts
city: New York City
country: United States
facility: Memorial Sloan Kettering Cancer Center (MSKCC)
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Melbourne
country: Australia
facility: University of Melbourne, Peter MacCallum Cancer Center
city: Antwerpen
country: Belgium
facility: Ziekenhuis Aan de Stroom
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: Women's College Hospital, University of Toronto
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Quebec
country: Canada
facility: CHU de Quebec Université laval
city: Lisbon
country: Portugal
facility: Champalimaud Foundation, University of Lisbon
Study officials:
References: