Genetic Information That Can Save Lives
BRCA1 and BRCA2 are tumor suppressor genes. When inherited mutations disable these genes, the lifetime risk of certain cancers — particularly breast and ovarian — rises dramatically. Identifying carriers allows for enhanced surveillance, prevention strategies, and treatment options that can prevent cancer or detect it early.
The criteria for BRCA testing have expanded substantially in recent years as we have learned more about who carries these mutations and how they affect care. At Zimmer Medical Group, we discuss BRCA testing with patients who meet criteria, coordinate testing, and help interpret results.
What BRCA1 and BRCA2 Do
These genes produce proteins that help repair DNA damage in cells. When mutated, the cell's ability to repair DNA is compromised, increasing the chance that a cell will become cancerous over time.
Lifetime cancer risks in BRCA mutation carriers:
BRCA1
- Breast cancer: 55–72%
- Ovarian cancer: 39–44%
- Increased risks of fallopian tube and peritoneal cancers
- Possible modest increase in pancreatic and prostate cancer
BRCA2
- Breast cancer: 45–69%
- Ovarian cancer: 11–17%
- Pancreatic cancer: 5–7%
- Prostate cancer in men: significantly increased
- Male breast cancer: 5–10%
- Melanoma: increased risk
For comparison, average lifetime breast cancer risk is about 13% in women and ovarian cancer risk is about 1.3%.
Who Should Be Tested
Current guidelines support testing patients meeting one or more of the following:
Personal Cancer History
- Breast cancer at age ≤ 50
- Triple-negative breast cancer at age ≤ 60
- Ovarian, fallopian tube, or peritoneal cancer at any age
- Male breast cancer
- Pancreatic cancer
- High-grade or metastatic prostate cancer
- Two or more primary cancers (breast, ovarian, pancreatic, prostate)
- Bilateral breast cancer
Family History
- Multiple relatives with breast, ovarian, pancreatic, or aggressive prostate cancer
- A first-degree relative with breast cancer at age ≤ 50
- A relative with ovarian cancer at any age
- A relative with male breast cancer
- A relative with two primary cancers
- A known BRCA mutation in the family
Ancestry Considerations
- Ashkenazi Jewish ancestry — substantially higher carrier rates (about 1 in 40 vs. 1 in 400 in general population). Testing the three founder mutations is sometimes appropriate even without strong family history
- Other founder populations (Icelandic, French Canadian, certain other groups)
Other Considerations
- Family history involving multiple generations
- Family history with limited information that nonetheless suggests pattern (small family, adopted, unknown family medical history)
How Criteria Have Expanded
Older guidelines focused tightly on patients with strong family histories. We now know that:
- Many BRCA mutation carriers have no significant family history (small families, mostly male relatives, adopted, etc.)
- Restrictive criteria miss many carriers
- The information value of testing extends to family members
- Testing is more accessible and less expensive than in the past
Current criteria are more inclusive than they were a decade ago. The trend continues toward broader testing eligibility.
Pre-Test Considerations
Before testing, important discussions:
What Will You Do With the Information?
Knowing your status only helps if it leads to actionable changes:
- Enhanced surveillance
- Risk-reducing surgery consideration
- Family member testing
- Lifestyle and chemoprevention discussions
- Treatment planning if cancer is present
Insurance and Financial Considerations
- Most insurance plans cover testing for patients meeting criteria
- The Genetic Information Nondiscrimination Act (GINA) protects against health insurance and employment discrimination
- GINA does not protect life, disability, or long-term care insurance
- Some patients consider purchasing these insurances before testing
Family Implications
- Positive results have implications for relatives
- Discussions about how and when to share results
- Cascade testing of family members is highly cost-effective and impactful
The Testing Process
Genetic Counseling
Pre-test genetic counseling is recommended:
- Available through dedicated genetic counselors, telehealth services, or some primary care/specialty offices
- Reviews family history thoroughly
- Discusses what testing will and won't tell you
- Explains implications of various results
- Helps prepare for emotional implications
The Test Itself
- Blood or saliva sample
- Most laboratories now sequence not just BRCA1 and BRCA2 but a broader panel of cancer susceptibility genes
- Expanded panel approaches catch other significant mutations (PALB2, ATM, CHEK2, others) that affect cancer risk
Results
Possible results:
- Positive (pathogenic mutation): confirmed cancer susceptibility
- Negative (no mutation found): generally reassuring, particularly with strong family history if the family mutation is known
- Variant of uncertain significance (VUS): a genetic change whose meaning is unclear; should not be used to guide medical decisions; may be reclassified over time
What to Do With a Positive Result
Enhanced Surveillance for Women
- Annual breast MRI starting age 25–30
- Annual mammogram starting age 30 (often staggered with MRI every 6 months)
- Clinical breast exams every 6 months
- See our breast cancer screening article for context
- Pelvic exam, transvaginal ultrasound, CA-125 every 6 months for ovarian cancer surveillance (limited effectiveness)
Risk-Reducing Surgery Options
- Bilateral risk-reducing mastectomy — reduces breast cancer risk by 90+ percent
- Bilateral salpingo-oophorectomy (BSO) — reduces ovarian/fallopian tube cancer risk by 80+ percent and reduces breast cancer risk if performed before menopause
- Decisions involve cancer risk reduction vs. surgical risks, hormonal effects, and personal values
- Timing of BSO typically considered after completion of childbearing
Chemoprevention
- Tamoxifen or raloxifene to reduce breast cancer risk
- Less commonly used than surveillance and surgery; risk/benefit considerations
For Men
- Enhanced prostate cancer screening — see PSA screening
- Breast self-awareness and clinical exams
- Pancreatic cancer screening in selected high-risk patients (BRCA2 + family history)
For Both Sexes
- Discussion of pancreatic cancer screening when family history supports it
- Skin cancer surveillance
- Family member cascade testing
What a Negative Result Means
Interpretation depends on context:
"True Negative"
If a family mutation is known and you don't have it: cancer risk is similar to the general population. Standard screening recommendations apply.
"Uninformative Negative"
If no family mutation is known and your test is negative: cancer risk depends on family history. May still warrant enhanced screening based on family pattern. Other genes may be involved.
This is why testing an affected family member when possible is important — it makes results in unaffected relatives easier to interpret.
Limitations and Evolving Knowledge
- Testing covers known genes; new susceptibility genes continue to be identified
- Variants of uncertain significance can be confusing; periodic re-interpretation may help
- Cancer risk estimates may continue to be refined
- Treatment options for BRCA-related cancers continue to expand (PARP inhibitors, etc.)
When to See Your Doctor
- Personal history of cancer at young age
- Multiple family members with breast, ovarian, pancreatic, or aggressive prostate cancer
- Ashkenazi Jewish ancestry plus any family cancer history
- Already known BRCA mutation in the family
- Difficulty interpreting prior testing results
- Considering management decisions based on testing
The National Comprehensive Cancer Network and the American Society of Clinical Oncology provide detailed criteria and patient resources for genetic testing decisions.
Family history that suggests genetic cancer risk? Contact Zimmer Medical Group for an evaluation, appropriate testing referral, and coordinated care if testing identifies a mutation.
