PATHCHAT Edition
Published: 2024
Please contact your local Ampath pathologist for more information.
The Importance of Genetic Testing in Breast Cancer
✅ Breast Cancer Overview
- Breast cancer is the most frequently diagnosed cancer worldwide.
- It remains a leading cause of cancer-related mortality.
- A complex and heterogeneous disease with strong genetic influences.
✅ The Role of Next-Generation Sequencing (NGS)
- Enhances understanding of breast cancer at the molecular level.
- Identifies pathogenic genetic variants (mutations) associated with disease predisposition.
- Enables targeted therapy for improved treatment outcomes.
📌 Genetic testing in breast cancer helps in both risk assessment and personalised treatment strategies.
Somatic vs. Germline Genetic Testing
✅ Somatic Genetic Testing
- Identifies mutations found within the tumour itself (not inherited).
- Mutations arise from environmental or lifestyle factors (e.g., smoking, radiation).
- Performed on tumour tissue or circulating tumour DNA (liquid biopsy).
- Provides information on:
- Recurrence risk.
- Prognosis.
- Targeted therapy options.
✅ Germline Genetic Testing
- Identifies inherited mutations present in all cells from birth.
- Performed on a blood sample (EDTA).
- Used for risk evaluation in individuals with or without cancer.
- Facilitates:
- Early detection strategies.
- Preventative medical or surgical interventions.
- Family risk assessment and genetic counselling.
📌 Both somatic and germline genetic testing play crucial roles in breast cancer management.
BRCA1/BRCA2 Tumour Testing and Germline Confirmation
✅ What If a BRCA1/BRCA2 Variant is Identified in Tumour Tissue?
- Tumour-based BRCA1/BRCA2 testing cannot distinguish between inherited (germline) and acquired (somatic) mutations.
- If the variant frequency in the tumour is high (~50%), germline confirmatory testing is recommended.
- If the variant frequency is low, it is likely a somatic variant, requiring no further testing.
📌 Confirmatory germline testing ensures appropriate genetic counselling and risk assessment for relatives.
Genetic Testing Panels for Breast Cancer
Germline Testing Panels
✔ Comprehensive Breast Cancer Panel (Mnemonic: BREAST)
- Includes genes: BRCA1, BRCA2, PTEN, TP53, CDH1, PALB2, RAD51C, RAD51D, STK11.
- Indications:
- Hereditary breast/ovarian cancer syndrome.
- Cowden syndrome.
- Li-Fraumeni syndrome (TP53-related).
- CDH1-associated cancers.
- PALB2-associated breast cancer.
- Peutz-Jeghers syndrome.
- Specimen: EDTA blood (5 mL).
✔ Full BRCA1/BRCA2 Panel (Mnemonic: ONCOBRCA)
- Includes copy number variant analysis (MLPA).
- Indications:
- Hereditary breast/ovarian cancer syndrome.
- Somatic BRCA testing on tumour tissue.
- Specimen: EDTA blood (5 mL) or FFPE tissue (4–6 slides).
✔ Targeted BRCA Testing for Afrikaner/Ashkenazi Jewish Ancestry (Mnemonic: BRCAFDR)
- Tests for common BRCA1/BRCA2 variants found in these populations.
- Specimen: EDTA blood (5 mL).
✔ ATM-Related Cancer Testing (Mnemonic: ATMNGS)
- Indications:
- ATM mutations associated with breast, prostate, and pancreatic cancer.
- Ataxia-telangiectasia (autosomal recessive inheritance).
- Specimen: EDTA blood (5 mL).
✔ Specific Familial Variant Testing (Mnemonic: DNAMUT)
- Used for previously identified familial pathogenic variants.
- Requires submission of a copy of the original genetic report.
- Specimen: EDTA blood (5 mL).
✔ Pharmacogenomics Panel for Tamoxifen Metabolism (Mnemonic: PHARMA)
- Includes CYP2D6 gene (affects tamoxifen metabolism).
- Genetic variations impact enzyme activity, influencing drug efficacy.
- Specimen: EDTA blood (5 mL).
📌 Germline testing enables early cancer risk assessment, family screening, and risk-reduction strategies.
Somatic (Tumour) Testing for Targeted Therapy
Actionable Genomic Alterations in Breast Cancer
✔ HER2 (ERBB2) Amplification
- Tests:
- Oncomine™ Precision Assay (Mnemonic: OPANGS).
- HER2 Fluorescence in Situ Hybridisation (FISH) (Mnemonic: HER2 FISH).
- Approved therapies:
- Trastuzumab, Pertuzumab, Lapatinib, Neratinib.
✔ BRCA1/BRCA2 Mutations
- Test: BRCA1/BRCA2 gene sequencing (Mnemonic: ONCOBRCA).
- Approved therapy: Olaparib.
✔ PIK3CA Mutations
- Tests:
- PIK3CA NGS (Mnemonic: EGFRASSEQ).
- Oncomine™ Precision Assay (Mnemonic: OPANGS).
- Approved therapy: Alpelisib.
✔ NTRK Fusions
- Test: Oncomine™ Precision Assay (Mnemonic: OPANGS).
- Approved therapies: Larotrectinib, Entrectinib.
📌 Somatic genetic testing identifies treatment targets, enabling precision oncology.
Contact Information
✅ For Genetic Testing Queries
- Ampath NGS Laboratory: 012 678 0645
- Email: ngs@ampath.co.za
✅ For Genetic Counselling
- Email: geneticsclinic@ampath.co.za
📌 Genetic testing in breast cancer enhances early detection, personalised treatment, and risk management strategies for patients and their families.