New cancer risk estimates for BRCA1/2 mutation carriers

Expert Guidelines

The National Comprehensive Cancer Network (NCCN) provides breast cancer risk management guidelines for people with BRCA1 and BRCA2 mutations. We recommend that you speak with a genetics expert who can look at your personal and family history of cancer and can help you to determine the best risk management plan. 

Screening for women:

• Learn to be aware of changes in breasts beginning at age 18.
• Clinical breast exam every 6-12 months beginning at age 25.
• Annual breast MRI with contrast (or mammogram if MRI is unavailable) beginning at age 25 and continuing until age 75.
• Annual mammogram at age 30 until age 75 (consider 3D mammography if available).
• Screening after age 75 should be considered on an individual basis.

Risk reduction for women:

• Women should have a discussion with their doctors about of the advantages and disadvantages of risk-reducing mastectomy.
  • Research has shown that risk-reducing mastectomy can lower the risk for breast cancer in high risk women by about 90%. Despite this, mastectomy has not been shown to help high risk women live longer.
  • Even after mastectomies, some breast tissue-and therefore some breast cancer risk remains. 
• Women should have a conversation with their doctor about the possible benefits of tamoxifen or other estrogen-blocking drugs to reduce breast cancer risk in women with BRCA2 mutations. Research on the benefit of these drugs to reduce breast cancer risk in women with BRCA1 mutations has been mixed.

Risk management in men:

• Breast self-exam training and education beginning at age 35.
• Clinical breast exam every 12 months beginning at age 35.
• In men with enlarged breasts, (gynecomastia) consider annual mammogram in men with gynecomastia beginning at age 50 or 10 years younger then the earliest case of male breast cancer in the family (whichever comes first). 

The National Comprehensive Cancer Network (NCCN) provides guidelines for management of gynecologic cancer risk in people with BRCA1 and BRCA2 mutations. 

Prevention 

• Risk-reducing removal of ovaries and fallopian tubes, (known as salpingo-oophorectomy) is recommended between ages 35-40 for BRCA1 and 40-45 for BRCA2 and upon completion of childbearing.
  • Research studies show that removing the ovaries can increase survival for women with BRCA1 mutations. 
  • Women should talk with their doctors about the effects of early menopause and options for managing them.
• Women should talk with their doctors about the risks and benefits of keeping or removing their uterus (hysterectomy), including:
  • Women with a BRCA1 mutation have an increased risk for a rare form of aggressive uterine cancer; hysterectomy removes this risk. 
  • For women considering hormone replacement after surgery, the presence or absence of a uterus can affect the choice of hormones used.
    • Estrogen-only hormone replacement is less likely to increase the risk for breast cancer, although it increases the risk for uterine cancer. Women who still have their uterus are typically given hormone replacement with both estrogen and progesterone.
    • Adding progesterone to estrogen hormone replacement can protect against uterine cancer. However, the combination of these hormones may increase the risk for breast cancer more than estrogen alone. 
  • A medical history of fibroids or other uterine or cervical issues may justify a hysterectomy. 
• Oral contraceptives (birth control pills) have been shown to lower the risk for ovarian cancer in women with BRCA1 mutations. Research on the effect of oral contraceptives on breast cancer risk has been mixed. Women should discuss the benefits and risks of oral contraceptives for lowering ovarian cancer risk with their doctors. 
• Removal of the fallopian tubes only (salpingectomy) is being studied as an option for lowering risk in high-risk women who are not ready to remove their ovaries. Studies on the effects of salpingectomy are ongoing. At this time whether salpingectomy lowers the risk for ovarian cancer in high-risk women remains unknown. 
  • Consider enrolling in a research study looking at this procedure to lower cancer risk.

Screening

• There are no proven benefits to routine ovarian cancer screening using transvaginal  and a CA-125 blood test. However, some doctors still recommend this screening, starting at ages 30-35.
• Women should be aware of the symptoms of gynecologic cancer and report abnormalities to their doctors. 

Questions To Ask Your Health Care Provider

• What is my risk for developing breast, ovarian, contralateral breast or other cancers?
• What are my options for managing my risk for these cancers?
• Was my particular family history of cancer included in estimating my cancer risk?
• Does the type of mutation or the location of the mutation on the gene affect my cancer risk?

Open Clinical Trials

Below are clinical trials that include genetic counseling and testing.

• NCT02665195: Prospective Registry Of MultiPlex Testing (PROMPT). PROMPT is an online research registry. The goal of PROMPT is to help researchers to better understand the risks that are linked to mutations in less well-studied genes. 
• NCT04245176: Genetic Testing for All Breast Cancer Patients (GET FACTS). This study looks at the impact of a novel genetic counseling method on surgical decisions in people with newly diagnosed breast cancer. This study involves genetic counseling about contralateral breast cancer risk. 
• NCT02620852: WISDOM Study: Women Informed to Screen Depending on Measures of Risk offers women age 40-74 the opportunity to undergo risk assessment and genetic testing in order to determine the best breast screening options based on their situation.  
• Enhancing Genetic Risk Assessment in Underserved Blacks and Latinas at Risk of Hereditary Breast Cancer. This study will test how well educational materials increase the use of knowledge about hereditary cancer risk.
• NCT04476654: Improving Uptake of Genetic Cancer Risk Assessment in African American Women-Video. This study looks at the usefulness of intervention with a culturally-tailored video to improve uptake of genetic counseling in Black women who are at increased risk of HBOC.

Other genetic counseling or testing studies may be found here.