Is cancer antigen 125 (CA‑125), human epididymis protein 4 (HE4), or the Risk of Ovarian Malignancy Algorithm (ROMA) a good screening tool for a 56‑year‑old asymptomatic woman whose mother died of ovarian cancer at age 52?

Screening for Ovarian Cancer in High-Risk Women

No, CA-125, HE4, and ROMA are not recommended as screening tools for this 56-year-old asymptomatic woman, even with her significant family history of ovarian cancer. The U.S. Preventive Services Task Force gives a Grade D recommendation (recommends against) screening for ovarian cancer in all asymptomatic women, including those with a family history, because screening does not reduce mortality and causes significant harms 1.

Why Screening Is Not Recommended

The evidence against screening is definitive:

• Annual screening with transvaginal ultrasound and CA-125 does not decrease ovarian cancer mortality, even in women with family history 1, 2
• In the only randomized trial reporting mortality outcomes, 17% of participants had a family history of ovarian or breast cancer, and no mortality benefit was observed in the overall trial or this subgroup 1
• The PLCO trial of 78,216 women demonstrated no reduction in ovarian cancer mortality with annual CA-125 and transvaginal ultrasound screening, with a relative risk of 1.18 2

The harms of screening substantially outweigh any potential benefits:

• For every 10,000 women screened annually, 300 (using CA-125) or 350 (using ultrasound) women without cancer will be recalled for further testing, causing significant anxiety 1, 2
• Of these, 20 (CA-125) or 65 (ultrasound) women without cancer will undergo unnecessary surgery each year 1, 2
• The positive predictive value is only 2% in average-risk women, meaning 98% of positive screening tests are false positives 1

Specific Guidance for This Patient's Risk Profile

Her family history does place her at increased risk, but this does not change the screening recommendation:

• Having one first-degree relative (her mother) with ovarian cancer increases her lifetime risk from 1.6% to approximately 5% 1
• However, higher incidence does not translate to screening benefit—it may result in more diagnoses and treatments without reducing deaths, while actually leading to more harms 1

What You Should Do Instead

Refer for genetic counseling immediately 2:

• Her mother's young age at diagnosis (52 years) is particularly concerning for hereditary cancer syndrome
• She should be assessed for BRCA1/BRCA2 mutations and Lynch syndrome 1, 2
• Genetic testing should ideally be performed on an affected family member first (if available), then the patient undergoes targeted testing for that specific familial mutation 2

If BRCA mutation is confirmed:

• Risk-reducing salpingo-oophorectomy is the most effective intervention, typically recommended between ages 35-40 for BRCA1 carriers and 40-45 for BRCA2 carriers after childbearing is complete 2
• If she declines risk-reducing surgery, the National Comprehensive Cancer Network recommends concurrent transvaginal ultrasound plus CA-125 every 6 months starting at age 35 years—but only for confirmed BRCA mutation carriers, not for family history alone 2

Discuss proven risk-reduction strategies:

• Oral contraceptive use, pregnancy and breastfeeding history, and bilateral tubal ligation all reduce ovarian cancer risk 1

Clinical Vigilance Without Screening

Remain vigilant for symptoms that warrant evaluation 1:

• Bloating, pelvic or abdominal pain, difficulty eating, feeling full quickly, and urinary symptoms (urgency or frequency)
• These symptoms are concerning when they are new and frequent (>12 days per month) 1
• However, 95% of women in primary care report at least one of these symptoms within the previous year, so specificity is poor 1
• If these symptoms develop, evaluate with pelvic examination, CA-125, or ultrasound—but this is diagnostic evaluation, not screening 1

Why Other Markers Don't Help

HE4 and ROMA are not validated for screening:

• The Society of Gynecologic Oncologists and FDA explicitly state that these tests should not be used as screening tools 1
• While HE4 has higher specificity than CA-125 (93.6% vs 82.1%) for diagnosing existing ovarian cancer 3, recent data show that CA-125, HE4, and other markers do not increase early enough to be useful in detecting early-stage ovarian cancer 1
• ROMA has insufficient evidence to support screening in low-risk women, and the Society of Gynecologic Oncologists states that larger randomized controlled trials are needed before this approach can be recommended 1

Common Pitfalls to Avoid

• Do not order CA-125, HE4, or ROMA as screening tests in this asymptomatic woman—this violates guideline recommendations and will lead to false positives and unnecessary interventions 1
• Do not assume that family history justifies screening—the evidence shows no mortality benefit even in this higher-risk population 1, 2
• Do not delay genetic counseling referral—this is the appropriate next step, not ordering tumor markers 2