What is the risk of a 37-year-old female carrying a BRCA (Breast Cancer Gene) mutation if her mother died of ovarian cancer?

BRCA Mutation Risk in a 37-Year-Old Woman with Maternal Ovarian Cancer History

This patient has a significantly elevated risk of carrying a BRCA mutation and should be screened with a validated familial risk assessment tool, followed by genetic counseling and BRCA testing. 1

Understanding the Risk Context

A maternal history of ovarian cancer substantially increases this patient's likelihood of harboring a BRCA mutation compared to the general population. While the baseline prevalence of BRCA mutations in unselected women is only 0.2% to 0.3% (1 in 300-500), the risk increases dramatically when family history includes ovarian cancer. 1

In populations selected based on family history of breast or ovarian cancer, BRCA1 mutation prevalence reaches 13.6%, BRCA2 mutation prevalence reaches 7.9%, and the combined prevalence of either mutation is 19.8%. 1 This represents approximately a 60-100 fold increase over general population risk.

Specific Risk Factors Present

This patient meets high-risk criteria based on several key factors:

• First-degree relative (mother) with ovarian cancer - This alone is one of the strongest predictors of BRCA mutation carrier status 1, 2
• Maternal lineage cancer - Maternal family history of ovarian cancer confers significantly increased risk (p=0.037) compared to patients without such history 3
• Age consideration - At 37 years old, she is approaching the age where enhanced surveillance and risk-reduction strategies become critical, as BRCA1 carriers have 39% ovarian cancer risk by age 70 and BRCA2 carriers have 10-17% risk 1

Recommended Clinical Approach

Step 1: Immediate Risk Assessment Screening

Use a validated familial risk stratification tool to formally assess her candidacy for genetic counseling. The USPSTF recommends several tools with >85% sensitivity, including: 1

• Ontario Family History Assessment Tool
• Manchester Scoring System
• Referral Screening Tool
• Pedigree Assessment Tool
• FHS-7

Step 2: Genetic Counseling Referral

Women with positive screening results (which this patient will almost certainly have given maternal ovarian cancer) should receive genetic counseling from suitably trained providers. 1 This is a Grade B recommendation from USPSTF, meaning there is moderate certainty of moderate net benefit. 1

Step 3: BRCA Testing if Indicated

Following counseling, BRCA1 and BRCA2 mutation testing should be performed using: 1

• Direct DNA sequencing (gold standard)
• Multiplex ligation-dependent probe amplification (MLPA) to detect large genomic alterations, which account for 2-12% of high-risk families

Critical Clinical Implications

If testing reveals a BRCA1 mutation: 1

• 65% (44-78% CI) cumulative breast cancer risk by age 70
• 39% (18-54% CI) cumulative ovarian cancer risk by age 70
• Requires intensive surveillance starting at age 25-30 with annual mammography and MRI

If testing reveals a BRCA2 mutation: 1

• 45% (31-56% CI) cumulative breast cancer risk by age 70
• 11% (2.4-19% CI) cumulative ovarian cancer risk by age 70
• Same intensive surveillance protocol

Important Caveats and Pitfalls

Do not falsely reassure if testing is negative. More than 70% of familial breast/ovarian cancer cases remain unexplained genetically, and approximately 10% of unselected ovarian cancer patients have identifiable mutations. 4, 3 A negative BRCA test does not eliminate hereditary risk when strong family history persists. 4

Consider additional factors that modify interpretation: 2

• Ashkenazi Jewish ancestry increases baseline BRCA prevalence to 2.1% even without family history 1
• Limited family structure (small family size, predominance of male relatives) can mask hereditary predisposition 4, 2
• Testing technology evolves - previously undetectable mutations may now be identifiable with updated panels 4

If genetic testing is negative but family history remains concerning: 4

• Refer to cancer genetics specialist for comprehensive risk assessment
• Consider multigene panel testing for other hereditary cancer syndromes (TP53, PTEN, CDH1, STK11, PALB2, ATM, CHEK2) 4
• Implement enhanced surveillance based on calculated lifetime risk from family history alone
• Update family history annually as new cancer events may alter risk assessment 4, 2

The absence of additional affected relatives does not reduce her risk - even a single first-degree relative with ovarian cancer warrants full evaluation, as approximately 50% of BRCA1 mutation carriers with ovarian cancer had family histories considered "unremarkable" by conventional standards. 3