Test in focus: Genetic testing in breast cancer

🧬 Genetic Testing in Breast Cancer (BRCA1 & BRCA2 Testing)

🔍 Test in Focus

📚 Background

Breast cancer is the most frequently diagnosed cancer worldwide 🌍 and a leading cause of cancer-related deaths. It is genetically complex and often shows familial clustering 👨‍👩‍👧‍👦.
BRCA1/2-associated hereditary breast and ovarian cancer syndrome is an autosomal dominant disorder caused by germline mutations in the BRCA1 and BRCA2 genes, increasing the risk of developing breast and other cancers, especially before age 50 🎗️.

❓ Who Should Get Tested?

Patients concerned about harmful BRCA1/2 variants should consult a genetic counsellor 🧑‍⚕️. The NCCN recommends testing in the following cases:

1. 🧬 Blood relative with a known harmful variant.
2. 👩‍⚕️ Personal history of cancer:
   • Diagnosed ≤45 years.
   • Diagnosed 46–50 years with:
     • Unknown/limited family history.
     • Second breast cancer.
     • Close relatives with breast, ovarian, pancreatic, or prostate cancer.
   • Triple-negative breast cancer ≤60 years.
   • Any age with:
     • Ashkenazi Jewish ancestry ✡️.
     • Close relatives diagnosed ≤50 years.
     • Relatives with ovarian, pancreatic, or metastatic/intraductal prostate cancer.
     • 3+ breast cancer cases in the family.
     • Male breast cancer 👨‍⚕️.
3. 🧫 Ovarian, fallopian tube, or primary peritoneal carcinoma.
4. 🧪 Pancreatic ductal adenocarcinoma.
5. 🧍‍♂️ Prostate cancer (metastatic or intraductal).
6. 💊 Therapy decision-making (e.g., HER2-negative metastatic breast cancer).

🧾 What Do BRCA1 and BRCA2 Test Results Mean?

Results should be interpreted with a genetic counsellor:

• ✅ Positive / Pathogenic: Inherited harmful variant → increased cancer risk.
• ❌ Negative / Not Detected: No harmful variant → general population risk.
• ❓ Variant of Uncertain Significance (VUS): Unknown impact → further study needed.

📚 References

1. 🌐 Global cancer statistics 2020 – CA: Cancer Journal for Clinicians
2. 🧾 WHO Classification of Tumours – Breast Tumours, 5th ed.
3. 🇺🇸 US Preventive Services Task Force – BRCA-related cancer testing
4. 📘 NCCN Guidelines – Genetic/familial high-risk assessment

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