Is genetic testing necessary for a patient with a family history of uterine cancer who has undergone a hysterectomy?

Genetic Testing for Patients with Family History of Uterine Cancer Who Have Had a Hysterectomy

Yes, genetic testing is still recommended for a patient with a family history of uterine cancer who has undergone a hysterectomy, as it can identify hereditary cancer syndromes that increase risk for other cancers beyond the uterus.

Rationale for Genetic Testing Post-Hysterectomy

Even though the patient has had a hysterectomy and no longer has risk for uterine cancer, genetic testing remains important for several reasons:

1. Lynch Syndrome Identification:

   • Approximately 5% of endometrial cancers are associated with Lynch syndrome (hereditary non-polyposis colorectal cancer/HNPCC) 1
   • Lynch syndrome increases risk for multiple other cancers beyond endometrial cancer

2. Risk Assessment for Other Cancers:

   • Patients with Lynch syndrome have increased risk for:
     • Colorectal cancer (up to 80% lifetime risk)
     • Ovarian cancer (up to 12% lifetime risk)
     • Gastric cancer
     • Small bowel cancer
     • Urinary tract cancers

3. Risk Assessment for Family Members:

   • Identifying a hereditary syndrome allows for cascade testing of relatives
   • Early surveillance and risk-reducing interventions can be offered to family members

Testing Approach

When to Consider Testing

Testing is particularly indicated if:

• Mother had uterine cancer diagnosed before age 50
• Multiple family members with Lynch-associated cancers (colorectal, endometrial, ovarian, gastric, urinary tract)
• Family history of multiple Lynch-associated cancers in the same individual
• Known Lynch syndrome mutation in the family

Testing Process

1. Initial Assessment:

   • Detailed family history focusing on cancer types, ages at diagnosis, and lineage
   • Consider using validated screening tools to assess hereditary cancer risk

2. Genetic Counseling:

   • Discuss implications of testing
   • Review potential results and their impact on medical management
   • Address psychological aspects of genetic testing

3. Testing Strategy:

   • Multi-gene panel testing that includes Lynch syndrome genes (MLH1, MSH2, MSH6, PMS2, EPCAM)
   • Consider broader panels that include other genes associated with gynecologic cancers

Management Based on Results

If Positive for Lynch Syndrome:

• Colorectal Cancer Screening:

  • Colonoscopy every 1-2 years beginning at age 20-25 1

• Other Cancer Surveillance:

  • Upper GI endoscopy every 2-4 years beginning at age 30-40 1
  • Consider urinalysis and cytology annually

• For Female Relatives with Intact Uterus/Ovaries:

  • Endometrial biopsy every 1-2 years starting at age 30-35 1
  • Consider risk-reducing hysterectomy and bilateral salpingo-oophorectomy after childbearing is complete 1

If Negative:

• Standard cancer screening based on general population guidelines
• Consider more intensive screening if family history remains concerning despite negative genetic testing

Common Pitfalls to Avoid

1. Assuming hysterectomy eliminates need for genetic testing:

   • This overlooks risks for other cancers and implications for family members

2. Focusing only on uterine cancer history:

   • A comprehensive cancer family history across all cancer types is essential

3. Limiting testing to only Lynch syndrome genes:

   • Consider broader panel testing as multiple genes can increase gynecologic cancer risk

4. Overlooking maternal and paternal family history:

   • Lynch syndrome and other hereditary cancer syndromes can be inherited from either parent

Conclusion

Genetic testing remains valuable for patients with a family history of uterine cancer even after hysterectomy. The NCCN guidelines recommend universal testing of endometrial carcinomas for mismatch repair deficiency 1, and genetic counseling and testing for patients with significant family history of endometrial and/or colorectal cancer. Identifying hereditary cancer syndromes allows for appropriate cancer surveillance and risk-reducing strategies for both the patient and their at-risk family members.