Breast Cancer Surgery
Conditions
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
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.
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.
Sponsors
Sir Mortimer B. Davis - Jewish General Hospital
Cancer Research Society
Quebec Breast Cancer Foundation
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of breast cancer following RRM | 10 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of RRM | 10 years | To evaluate uptake of RRM versus active surveillance amongst an international cohort of unaffected women with high-penetrance GPVs in BRCA1/2, PALB2, CDH1, PTEN, or TP53 |
| Incidence of post-operative complications | 10 years | To evaluate post-operative complications and supplemental surgery following NSM, SSM, and total mastectomy in those undergoing RRM |
| Incidence of pathologic outcomes following NSM | 10 years | To evaluate pathologic outcomes following RRM, including the presence of high-risk lesions or occult in situ and/or invasive malignancy |
| Number of participants using endocrine prevention | 10 years | To explore the use of endocrine prevention in unaffected women with high-penetrance GPVs in BRCA1/2, PALB2, CDH1, PTEN, or TP53 who elect to undergo active surveillance |
| Number of participants who have undergone pre-mastectomy imaging and post-mastectomy surveillance | 10 years | To assess practices in pre-mastectomy imaging and post-mastectomy surveillance, including the number of participants who underwent preoperative MRI and mammography as well as post-mastectomy surveillance, including MRI, ultrasound and chest wall examination. |
Countries
Australia, Belgium, Canada, Japan, Portugal, South Korea, United Kingdom, United States
Contacts
CONTACTStephanie Wong, MD
CONTACTSarah Sabboobeh, MSc
Outcome results
None listed