Prophylactic Mastectomy and BRCA – Risk Reduction and Guidelines

CLINICAL ACTIONS:

A recent large prospective cohort study demonstrated that by age 80, the cumulative breast cancer risk for BRCA1 mutation carriers is 72% (95% CI, 65% to 79%) and 69% (95% CI, 61% to 77%) for BRCA2. In the context of women with high risk for breast cancer, consider the following:

Bilateral risk-reducing mastectomy (RRM) is an option for women at high risk for breast cancer
High-risk includes carriers of deleterious mutations in BRCA1, BRCA2 and other genes associated with high risk of breast cancer such as TP53, PTEN, CH1 or STK11
Prior to surgery, obtain the following
- Multidisciplinary consultations with genetic counseling, surgical reconstructive and oncology teams
- Clinical breast exam
- Bilateral mammogram if not performed within past 6 months
If no findings on clinical examination or imaging
- Women may choose to undergo RRM with or without immediate reconstruction
- Remove all breast tissue (total mastectomy)
- Axillary node assessment has limited utility at the time of RRM and only required if cancer identified on pathology
If patient at risk for occult primary cancer (abnormal imaging or positive family history without MRI imaging available)
- Sentinel note biopsy may be performed for axillary staging

SYNOPSIS:

There are other management options aside from RRM for women who are at high risk for breast cancer due to pathogenic variants in BRCA and related genes. Chemoprevention using risk reducing medications such as tamoxifen and raloxifene may be appropriate. Selection of these agents depends on age, race, breast cancer risk and history of hysterectomy. Aromatase inhibitors have also been investigated for use as risk reducing agents. However, these medications are more effective at preventing ER+ disease which is more highly associated with BRCA2 compared to BRCA1. Surveillance programs using imaging studies are also available. Monitoring with MRI is not a preventative strategy but rather an approach that can be used for early detection.

KEY POINTS:

RRM may not reduce the risk of all-cause mortality but can reduce the risk of breast cancer in BRCA carriers by 85 to 100%
NCCN and ACOG recommend that RRM be offered to women who are BRCA mutation carriers to reduce the risk of breast cancer
Shared decision making should include general health and life expectancy

Women at High Risk but Not BRCA Mutation Carriers

According to the National Cancer Institute, other women at high risk for breast cancer, aside from BRCA mutation carriers, who might consider risk reducing mastectomy include (see ‘Primary Sources – Learn More’ below)

Those with a strong family history of breast cancer (such as having a mother, sister, and/or daughter who was diagnosed with bilateral breast cancer or with breast cancer before age 50 years or having multiple family members with breast or ovarian cancer)

Those with lobular carcinoma in situ (LCIS) plus a family history of breast cancer

Those who have had radiation therapy to the chest (including the breasts) before the age of 30 years