What screening is necessary for a 48-year-old female with a likely pathogenic variant in the CHEK2 (Checkpoint Kinase 2) gene, specifically the c.190G>A (p.Glu64Lys) mutation?

Screening Recommendations for a 48-Year-Old Female with CHEK2 c.190G>A Pathogenic Variant

For a 48-year-old female with a likely pathogenic variant in the CHEK2 gene (c.190G>A), enhanced breast cancer screening is the primary recommendation, with colorectal cancer screening according to population guidelines and consideration of family history for other cancer risks. 1, 2

Breast Cancer Screening

Primary Recommendations

• Annual mammography starting immediately (if not already begun)
• Annual breast MRI alternating with mammography at 6-month intervals
• Clinical breast examination every 6-12 months
• Consider risk-reducing strategies based on comprehensive risk assessment using tools like CanRisk that incorporate:
  • Family history
  • CHEK2 variant type
  • Other risk factors

Risk Context

• CHEK2 pathogenic variants confer a moderate risk of breast cancer (2-3 fold increased risk compared to general population)
• The specific c.190G>A variant is likely pathogenic, requiring appropriate surveillance
• Risk is modified by family history and other factors 1

Colorectal Cancer Screening

• Standard colonoscopy screening starting at age 45 if no family history of colorectal cancer
• Enhanced screening (starting at age 40 or 10 years before earliest colorectal cancer diagnosis in a first-degree relative, repeating every 5 years) if:
  • Patient has a truncating CHEK2 variant (c.190G>A may qualify)
  • Family history of colorectal cancer exists 2

Additional Cancer Screening Considerations

For Female Patients

• No specific ovarian cancer screening is recommended based solely on CHEK2 status
• Risk-reducing salpingo-oophorectomy is not indicated based on CHEK2 status alone 2

For Family Members

• Recommend cascade genetic testing for first-degree relatives (siblings, children)
• Testing is particularly important for female relatives due to breast cancer risk 1

Important Clinical Considerations

Variant-Specific Factors

• The c.190G>A variant in CHEK2 is considered likely pathogenic
• CHEK2 pathogenic variants are associated with increased risk of:
  • Breast cancer (primary concern)
  • Colorectal cancer (moderate risk)
  • Possibly prostate cancer in male relatives 2

Common Pitfalls to Avoid

1. Don't underestimate risk based on lack of family history - CHEK2 variants can show variable penetrance and may present without strong family history 1
2. Don't apply BRCA1/2 management protocols - CHEK2 has different risk profiles and management needs
3. Don't neglect comprehensive risk assessment - Use tools like CanRisk to personalize screening recommendations 1
4. Don't overlook the impact of obesity - Research suggests obesity may increase breast cancer risk in CHEK2 carriers 3

Prognosis Considerations

• CHEK2 pathogenic variants have been associated with adverse prognosis in early-onset breast cancer 3
• This underscores the importance of vigilant screening to detect cancer at earlier stages

Follow-up Recommendations

• Annual reassessment of screening protocol
• Update risk assessment if family history changes
• Consider referral to high-risk breast clinic for ongoing management