Should a carrier of the Ataxia-Telangiectasia Mutated (ATM) gene with a family history of ovarian cancer undergo a bilateral salpingo-oophorectomy (BSO)?

ATM Gene Mutation Carriers and Risk-Reducing BSO

For ATM gene mutation carriers with a family history of ovarian cancer, bilateral salpingo-oophorectomy (BSO) is not routinely recommended as there is insufficient evidence supporting an increased ovarian cancer risk specifically associated with ATM mutations.

Risk Assessment for ATM Mutation Carriers

ATM gene mutations are primarily associated with increased breast cancer risk, but unlike BRCA1/2 mutations, they do not confer a significantly elevated ovarian cancer risk that would warrant prophylactic BSO. The current guidelines make specific recommendations for different gene mutations:

• BRCA1/2 carriers: BSO recommended at age 35-40 for BRCA1 and 40-45 for BRCA2 1
• Lynch syndrome genes (MLH1, MSH2, MSH6): BSO recommended at age 40 for MLH1/MSH2 and age 50 for PMS2 1
• Other ovarian cancer risk genes (BRIP1, RAD51C, RAD51D): BSO recommended at age 45-50 1
• ATM gene: No specific recommendation for BSO based on this mutation alone 1

Family History Considerations

While a family history of ovarian cancer at age 50 is concerning, the current guidelines do not support BSO based solely on:

• ATM mutation carrier status
• A single second-degree relative (grandmother) with ovarian cancer

The family history should be evaluated more comprehensively to determine if there might be other genetic factors at play beyond the known ATM mutation.

Risks of Premature BSO

Performing BSO in premenopausal women carries significant long-term health risks:

• Premature menopause leading to increased risk of:
  • Cardiovascular disease
  • Osteoporosis and bone fractures
  • Cognitive dysfunction
  • Early mortality 2
• Sexual dysfunction requiring potential interventions 3
• Negative impact on quality of life 4

Management Algorithm

1. Risk assessment: ATM mutation alone does not warrant BSO

2. Surveillance options:

   • Annual gynecologic examination
   • Prompt evaluation of any abnormal symptoms
   • Consider transvaginal ultrasound and CA-125 only if additional risk factors emerge

3. If patient strongly desires surgical intervention despite recommendations:

   • Consider risk-reducing salpingectomy with delayed oophorectomy as an investigational approach 5
   • Ensure thorough counseling about the lack of proven benefit for ATM carriers
   • Discuss the significant risks of premature menopause if BSO is performed

4. If BSO is ultimately performed:

   • Consider hormone replacement therapy to mitigate risks of premature menopause 4
   • Provide counseling about potential sexual dysfunction and available interventions 3

Important Caveats

• The risk-benefit ratio does not favor BSO in ATM mutation carriers without additional significant risk factors
• If the family history suggests a possible undetected Lynch syndrome or BRCA mutation, additional genetic testing may be warranted
• The patient should be counseled that retaining the uterus after BSO may lead to potential endometrial cancer risk if hormone replacement therapy is used 6

The decision regarding BSO should be based on established risk factors and evidence-based guidelines rather than fear or anxiety about cancer risk, with careful consideration of the significant long-term health impacts of premature surgical menopause.