What screening approach is recommended for a patient with a first-degree relative having ovarian and pancreatic cancer?

Screening Recommendations for Patients with First-Degree Relatives Having Ovarian and Pancreatic Cancer

Genetic testing should be the first step for any patient with a first-degree relative having both ovarian and pancreatic cancer, as this strongly suggests a hereditary cancer syndrome requiring specific screening protocols. 1

Initial Assessment and Genetic Testing

• The combination of ovarian and pancreatic cancer in a first-degree relative significantly increases the likelihood of hereditary cancer syndromes, particularly those involving BRCA1/2 mutations
• Germline mutations commonly found in pancreatic adenocarcinoma include BRCA1, BRCA2, CDKN2A, Lynch syndrome genes (MSH2, MLH1, MSH6, PMS2, EPCAM), ATM, PALB2, STK11, and TP53 1
• BRCA2 mutations are generally the most prevalent in families with pancreatic cancer (2-6%) 1
• Testing the affected relative (if living) is preferred, but testing the patient is appropriate if the affected relative is unavailable 1

Ovarian Cancer Screening Recommendations

• For patients without identified pathogenic variants:

  • Routine ovarian cancer screening with transvaginal ultrasound and CA-125 is not recommended as it does not decrease mortality and can lead to unnecessary surgical interventions 1
  • The USPSTF explicitly recommends against ovarian cancer screening in average-risk women (Grade D recommendation) 1

• For patients with identified pathogenic variants:

  • BRCA1/2: Risk-reducing salpingo-oophorectomy (RRBSO) should be considered after completion of childbearing, typically between ages 35-45 1
  • BRIP1, RAD51C, RAD51D: RRBSO should be considered at age 45-50 1
  • PALB2: RRBSO may be considered for postmenopausal women 1

Pancreatic Cancer Screening Recommendations

• Pancreatic cancer screening is recommended for:

  1. Individuals with pathogenic variants in BRCA1, BRCA2, ATM, PALB2, or TP53 who have at least one first- or second-degree relative with exocrine pancreatic cancer 1
  2. Individuals with STK11 mutations (regardless of family history) 1
  3. Individuals with CDKN2A mutations (regardless of family history) 1

• Screening protocol:

  • Modality: Annual contrast-enhanced MRI/MRCP and/or endoscopic ultrasound 1
  • Starting age:
    • For STK11 carriers: Age 35 or 5-10 years younger than the youngest affected relative 1
    • For BRCA1, BRCA2, ATM, PALB2, or TP53 carriers: Age 50 or 10 years younger than the youngest affected relative 1, 2
    • For CDKN2A carriers: Age 40 or 10 years younger than the youngest affected relative 1

Breast Cancer Screening Recommendations

• For women with identified pathogenic variants or strong family history:
  • Annual breast MRI starting at age 30 (or 5 years younger than the youngest affected family member) for carriers of PALB2, CDH1, PTEN, or STK11 mutations 1
  • Annual breast MRI starting at age 20 for TP53 mutation carriers 1
  • Consider risk-reducing mastectomy on a case-by-case basis 1

Important Considerations and Pitfalls

• Pancreatic cancer screening should be performed at high-volume centers with expertise in pancreatic imaging and management 1, 2
• False positives in pancreatic screening can lead to unnecessary procedures with potential morbidity and mortality (1-2%) 3
• Screening yield for pancreatic cancer is highest in older individuals (>65 years) 4
• The absence of a known pathogenic variant does not eliminate the need for screening if family history is significant 1
• Risk assessment tools such as CanRisk (https://www.canrisk.org/) can aid in individualized risk management 1

Algorithm for Screening Approach

1. Obtain detailed family history, focusing on cancer types, ages at diagnosis, and lineage
2. Refer for genetic counseling and testing for a panel including BRCA1/2, Lynch syndrome genes, PALB2, ATM, CDKN2A, and STK11
3. If pathogenic variant identified:
   • Implement specific screening protocols based on the gene involved
   • Refer to high-volume centers for pancreatic screening if indicated
4. If no pathogenic variant identified:
   • Consider screening based on family history alone
   • For pancreatic cancer: Consider screening if there are ≥2 affected relatives with pancreatic cancer 1, 2
   • For ovarian cancer: No screening recommended, but discuss risk-reducing surgery options based on family history strength 1

By following this evidence-based approach, you can provide appropriate screening recommendations that may lead to early detection of cancer in high-risk individuals while avoiding unnecessary procedures in those at lower risk.