Clinical Practice Guideline of BRCA1/2 Testing for Breast Cancer 2021

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Clinical Practice Guideline of BRCA1/2 Testing for Patients with Breast Cancer: Chinese Society of Breast Surgery (CSBrS) Practice Guideline 2021

Breast cancer remains the most prevalent cancer among women worldwide, with approximately 5% to 10% of cases linked to hereditary predisposition due to inherited germline mutations. Among these, about 15% involve mutations in the breast cancer susceptibility genes BRCA1 and BRCA2. Identifying individuals with BRCA1/2 mutations is crucial, as it enables risk reduction through targeted screening and preventive measures. The Chinese Society of Breast Surgery (CSBrS) has developed the Clinical Practice Guideline of BRCA1/2 Testing for Patients with Breast Cancer (Version 2021) to provide evidence-based recommendations for clinicians in China. This guideline was formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and aims to enhance the identification of high-risk individuals and improve genetic counseling practices.

Level of Evidence and Recommendation Strength
The guideline employs a standardized approach to classify the level of evidence and the strength of recommendations. The evidence levels range from I (highest) to IV (lowest), while the recommendation strength is categorized as A (strong) or B (weak). A committee of 78 members, including breast surgeons, medical oncologists, radiologists, pathologists, radiation therapists, and epidemiologists, reviewed and voted on the recommendations. This diverse expertise ensures the guideline’s comprehensiveness and applicability to clinical practice.

Indications for BRCA1/2 Testing
The guideline outlines specific indications for BRCA1/2 testing, emphasizing the importance of identifying high-risk individuals. These indications are based on age, family history, and tumor characteristics. Key recommendations include:

  1. Testing for breast cancer patients diagnosed at or before 45 years old (Level of Evidence: I, Recommendation Strength: A).
  2. Testing for patients diagnosed between 46 and 50 years old if they have additional risk factors, such as a second primary breast cancer, a family history of breast cancer, or an unknown or limited family history (Level of Evidence: I, Recommendation Strength: A).
  3. Testing for patients diagnosed at or before 60 years old with triple-negative breast cancer (Level of Evidence: I, Recommendation Strength: A).
  4. Testing for patients of any age with a family history of breast cancer diagnosed at or before 50 years old, ovarian carcinoma, metastatic prostate cancer, pancreatic cancer, or male breast cancer (Level of Evidence: I, Recommendation Strength: A).
  5. Testing for male breast cancer patients (Level of Evidence: I, Recommendation Strength: A).
  6. Testing for patients with HER2-negative recurrent metastatic breast cancer (Level of Evidence: II, Recommendation Strength: A).
  7. Testing for patients with BRCA1/2 pathogenic or likely pathogenic variants detected in tumor tissues (Level of Evidence: I, Recommendation Strength: A).
  8. Testing for individuals from families with known BRCA1/2 pathogenic or likely pathogenic variants (Level of Evidence: I, Recommendation Strength: A).
  9. Testing for patients with ovarian carcinoma (Level of Evidence: I, Recommendation Strength: A).
  10. Testing for high-grade prostate cancer patients with a family history of ovarian carcinoma, pancreatic cancer, metastatic prostate cancer, or breast cancer diagnosed before 50 years old (Level of Evidence: I, Recommendation Strength: A).

These recommendations are designed to ensure that individuals at high risk of BRCA1/2 mutations are identified early, enabling timely interventions and risk management.

Risk Control for BRCA1/2 Mutation Carriers
The guideline provides detailed recommendations for risk control strategies in BRCA1/2 mutation carriers. These strategies focus on early detection and preventive measures to reduce the risk of developing breast cancer. Key recommendations include:

  1. Breast awareness starting at 18 years old, with physical examinations every 6 to 12 months beginning at age 25 (Level of Evidence: I, Recommendation Strength: A).
  2. Annual breast MRI screening with contrast starting at age 30 (Level of Evidence: I, Recommendation Strength: A).
  3. Annual breast MRI screening with contrast starting at age 25 if a close relative was diagnosed with breast cancer before age 30 (Level of Evidence: II, Recommendation Strength: B).
  4. Annual clinical breast examinations for male carriers starting at age 35 (Level of Evidence: II, Recommendation Strength: A).
  5. Prophylactic mastectomy combined with immediate breast reconstruction as a risk-reducing option (Level of Evidence: II, Recommendation Strength: B).

These strategies are tailored to the individual’s age, family history, and specific risk factors, ensuring a personalized approach to risk management.

Surgical Options for Breast Cancer Patients with BRCA1/2 Mutation
The guideline also addresses surgical options for breast cancer patients with BRCA1/2 mutations, emphasizing the importance of balancing cancer control with quality of life. Key recommendations include:

  1. Breast-conserving surgery with adjuvant radiotherapy for the whole breast (Level of Evidence: I, Recommendation Strength: A).
  2. Mastectomy as a primary surgical option (Level of Evidence: I, Recommendation Strength: A).
  3. Mastectomy combined with immediate breast reconstruction (Level of Evidence: I, Recommendation Strength: A).
  4. Contralateral prophylactic mastectomy with or without immediate breast reconstruction (Level of Evidence: II, Recommendation Strength: B).

These recommendations aim to provide patients with effective surgical options while considering their preferences and long-term outcomes.

Discussion and Considerations
The guideline highlights the importance of considering national conditions and referencing international guidelines and expert consensus when determining indications for BRCA1/2 testing. It also emphasizes the need for individualized risk control strategies, particularly for older patients over 75 years of age. The guideline acknowledges the limitations of certain screening modalities, such as mammography, in younger patients due to radiation exposure risks and lower sensitivity for detecting BRCA-associated tumors. Instead, breast MRI and ultrasound are recommended as primary imaging tools for this population.

The guideline also addresses the role of prophylactic mastectomy in reducing breast cancer risk. While studies have shown that bilateral risk-reducing mastectomy can decrease breast cancer risk by at least 90% in BRCA1/2 mutation carriers, it does not significantly reduce all-cause mortality. Additionally, the guideline notes that carrying a BRCA1/2 mutation is not significantly associated with nodal metastasis, and therefore, sentinel lymph node biopsy is not recommended during risk-reducing mastectomy.

For breast cancer patients with BRCA1/2 mutations, the guideline supports breast-conserving surgery with adjuvant therapy as a viable option. However, contralateral prophylactic mastectomy may be considered based on individual risk factors and preferences. Immediate breast reconstruction is recommended if prophylactic mastectomy is performed, to enhance patients’ quality of life and psychological well-being.

Conclusion
The Clinical Practice Guideline of BRCA1/2 Testing for Patients with Breast Cancer (Version 2021) provides comprehensive, evidence-based recommendations for identifying high-risk individuals, managing risk in BRCA1/2 mutation carriers, and selecting appropriate surgical options for breast cancer patients. By incorporating the latest research and expert consensus, the guideline aims to improve clinical outcomes and enhance the quality of care for patients with breast cancer in China.

doi.org/10.1097/CM9.0000000000001587

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