CLINICAL ACTIONS:

A recent large prospective cohort study (see ‘Related ObG Project’ below) demonstrated that by age 80, the cumulative breast cancer risk for BRCA1 mutation carriers is 72% (95% CI, 65%-79%) and 69% (95% CI, 61%-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 

Learn More – Primary Sources:

ACOG Practice Bulletin 182: Hereditary Breast and Ovarian Cancer Syndrome

NCCN Guidelines For Detection, Prevention, & Risk Reduction: Breast Cancer Risk Reduction

NCI: Surgery to Reduce the Risk of Breast Cancer

Related ObG Topics:

BRCA1 & BRCA2 Mutations: What Are the Risks for Developing Breast and Ovarian Cancer?

Cascade Testing: Notifying and Counseling Relatives of Individuals who are BRCA Mutation Carriers

Could Early Exome Sequencing Improve Detection and Prevention of BRCA1/2 Breast Cancer?

Should We Be Testing Beyond BRCA1/2 in Women of Ashkenazi Jewish Heritage with Breast Cancer?

USPSTF Guidelines for Primary Care Clinicians: BRCA-Related Cancer Risk Assessment