Genetic Risk Assessment and Counseling Referral
The most appropriate initial step is to perform genetic risk assessment using a validated familial risk assessment tool, followed by referral for genetic counseling if the assessment is positive (Answer: None of the provided options are correct—the correct answer is genetic risk assessment/counseling referral). 1, 2
Why Screening Tests Are Inappropriate
The USPSTF gives a Grade D recommendation against ovarian cancer screening (pelvic ultrasound and CA-125) in all asymptomatic women, including those with family history, because screening does not reduce mortality and causes significant harm. 1, 3
Approximately 10% of screened women receive false-positive results, leading to unnecessary surgeries with a 20:1 ratio of surgeries to screen-detected cancers. 2
In the only randomized trial reporting ovarian cancer mortality results, women with a family history of ovarian or breast cancer comprised 17% of participants, and the overall trial showed no mortality benefit. 1
Screening with transvaginal ultrasound or CA-125 does not decrease ovarian cancer mortality and leads to unnecessary major surgical interventions. 3
The Evidence-Based Approach: Genetic Risk Assessment
Primary care clinicians should assess women with a family history of ovarian cancer using an appropriate brief familial risk assessment tool, and women with positive results should receive genetic counseling and, if indicated after counseling, BRCA testing (USPSTF Grade B recommendation). 1, 4
Who Qualifies for Genetic Counseling Referral
Having a first-degree relative (mother, sister, daughter) with ovarian, fallopian tube, or primary peritoneal cancer represents one of the strongest family history criteria, requiring no additional affected relatives or age restrictions. 2
Women with two or more first- or second-degree relatives with ovarian cancer or a combination of breast and ovarian cancer should be considered for genetic counseling. 1, 5
For women of Ashkenazi Jewish descent, having a first-degree relative (or two second-degree relatives on the same side of the family) with breast or ovarian cancer warrants referral. 1, 5
Why This Matters for Mortality and Quality of Life
Risk-reducing salpingo-oophorectomy (RRSO) performed between ages 35-40 for BRCA1 carriers and 40-45 for BRCA2 carriers dramatically reduces ovarian cancer mortality—this is the evidence-based intervention, not screening. 2
The Impact of BRCA Mutations
BRCA1 mutation carriers have a cumulative lifetime ovarian cancer risk of 48.3% (38.8%-57.9%) by age 70. 5
BRCA2 mutation carriers have a cumulative lifetime ovarian cancer risk of 20.0% (13.3%-29.0%) by age 70. 5
Approximately 10% of ovarian cancers occur in association with BRCA1/BRCA2 mutations. 3, 6
BRCA mutation carriers also require enhanced breast cancer surveillance with MRI and mammography starting at age 25-30, which improves early detection and survival. 2
Optimal Testing Strategy
Initial genetic testing should ideally be performed on the affected family member (the mother with ovarian cancer) who has the highest likelihood of carrying a mutation. 2, 3
If the mother tests positive for a specific mutation, the patient can then undergo targeted testing for that familial mutation, which is faster and less expensive. 2, 3
If testing the affected relative is not possible, the asymptomatic patient can undergo comprehensive BRCA1/BRCA2 testing after genetic counseling. 1
Critical Pitfall: Family History Alone Is Insufficient
More than half of patients with BRCA1 mutations have family histories that would generally be considered unremarkable, and a routinely obtained family history is an unreliable way to identify patients who might harbor mutations. 6
In one study of unselected ovarian cancer patients, 19% of BRCA mutation carriers did not have a family history of hereditary breast or ovarian cancer. 7
When genetic counseling referral was restricted to women with family histories ascertained by surgeons, 14 mutation carriers were missed. 7
This is why formal genetic risk assessment tools and genetic counseling are superior to informal family history taking alone. 1, 4
What Genetic Counseling Entails
Pre-test counseling must cover the probability of finding a mutation, implications for the patient and family members, and meaning of possible results including variants of uncertain significance. 2
Discussion must address how results will influence medical management, including enhanced surveillance and risk-reducing surgeries. 2
Informed consent and genetic counseling must be completed before any BRCA testing. 2
Cascade testing should be offered to other at-risk family members if a mutation is identified. 2