Breast Cancer and Hereditary Gene Mutations (BRCA1/2 and Others)
Overview
- 90–95% of breast cancers are sporadic (no strong family history).
- 5–10% are hereditary, associated with germline mutations (e.g. BRCA1, BRCA2).
- Breast cancer itself is not directly inherited, but mutations that increase risk can be.
- Maternal and paternal family histories are equally relevant for assessing genetic risk.
What Constitutes a Strong Family History?
Consider referral to a familial cancer clinic if any of the following apply:
- Breast cancer < age 40
- Triple-negative breast cancer (TNBC)
- Multiple first-degree relatives with breast and/or ovarian cancer
- One individual with both breast and ovarian cancer
- Multiple cancers on the same side of the family: breast, ovarian, prostate, pancreatic, sarcoma, melanoma
- Male breast cancer
- Bilateral breast cancer
- Ashkenazi Jewish ancestry
Key Genes Associated with Breast Cancer Risk
| Gene | Cancer Risk / Syndrome Features |
|---|---|
| BRCA1 | ↑ Breast (up to 72%), ↑ Ovarian; common in triple-negative BC |
| BRCA2 | ↑ Breast (♀ ~70%, ♂ ~4%), ↑ Ovarian (~15%), ↑ Prostate (~25%), ↑ Pancreatic |
| PALB2 | ↑ Breast (~53%), ↑ TNBC, ↑ Male BC, ↑ Ovarian, ↑ Pancreatic |
| TP53 | Li-Fraumeni syndrome: early-onset BC (HER2+), other adult/childhood cancers |
| CDH1 | ↑ Invasive lobular BC (~40%), hereditary diffuse gastric cancer |
| PTEN | Cowden syndrome: ↑ BC, thyroid, uterus, bowel; benign tumours |
| STK11 | Peutz-Jeghers: ↑ BC, GI polyps and GI cancers |
| CHEK2 | ↑ Male BC, ↑ DCIS, moderate BC risk (17–30%) |
| ATM | ↑ BC, ↑ DCIS, ↑ Pancreatic (moderate risk) |
| RAD51C | ↑ TNBC, ↑ Ovarian cancer |
| NF1 | ↑ CNS tumours, ↑ BC (18% lifetime) |
| Uncertain Risk Genes | BARD1, BRIP1, Lynch genes (MLH1, MSH2, etc.), RAD51D – may be associated with BC |
BRCA1 vs BRCA2: Comparison Table
| Feature | BRCA1 | BRCA2 |
|---|---|---|
| Lifetime Breast Cancer Risk (♀) | Up to 72% | Up to 69% |
| Typical Age of Onset | Median ~40s | Later (~50s) |
| Common Subtype | Triple-negative (ER-/PR-/HER2-) | ER+/HER2- |
| MRI Screening | Start at age 25, yearly until 50+ | Same |
| Mammogram | Start at age 40, annually | Same |
| Breast Awareness | From age 18 | From age 18 |
| Risk-Reducing Mastectomy | Strongly considered (TNBC risk) | Considered if family history or dense breasts |
| Tamoxifen Use | Limited (less effective for TNBC) | More effective (ER+ tumours) |
MRI is particularly important for BRCA1:
- Earlier onset
- Higher breast density
- Fast-growing TNBC subtype
Mammography is more effective for BRCA2:
- Slower-growing, ER+ tumours
- More likely to occur at older age
Cancer Risk Management Strategies
For Women (BRCA1/2 carriers):
- Surveillance:
- MRI annually: age 25–50 (± ongoing after 50)
- Mammogram annually: age 40–74
- Clinical breast exams every 6–12 months
- Risk Reduction:
- Surgery: Risk-reducing mastectomy (RRM), RRSO (after age 40 or after childbearing)
- Medication: Tamoxifen (esp. for BRCA2), raloxifene
- Lifestyle: Smoking cessation, weight control, alcohol reduction
For Men (BRCA2 carriers):
- Screening:
- Annual PSA + DRE: from age 40
- Clinical breast exam; evaluate any breast lumps
Family Testing & Inheritance
- BRCA1/2 mutations are autosomal dominant:
Each child of a carrier has a 50% chance of inheriting the gene. - Offer predictive testing to first-degree relatives ≥18 years.
- Genetic counselling (pre- and post-test) is essential.
- Discuss reproductive options (e.g. IVF with pre-implantation genetic diagnosis – PGD).
Accessing Genetic Testing in Australia
Testing Access:
| Pathway | Eligibility | Cost |
|---|---|---|
| Public familial cancer clinic | Meets high-risk criteria (e.g. eviQ guidelines) | Medicare-covered |
| Private geneticist/specialist | Meets criteria | May be covered |
| Commercial provider (direct-to-consumer) | Not medically indicated | Out-of-pocket |
Public clinics provide:
- Comprehensive risk assessment
- Personalised screening/prevention plans
- Ongoing review and family cascade testing
Interpreting Genetic Test Results
| Result | Interpretation |
|---|---|
| Pathogenic variant | Mutation confirmed → ↑ cancer risk → family testing recommended |
| No pathogenic variant | No known mutation → routine population screening; no cascade testing |
| Variant of Uncertain Significance (VUS) | Not actionable; no family testing; monitor for updated evidence |
⚖️ Genetic Testing and Insurance in Australia
| Timeframe | Insurance Impact |
|---|---|
| Pre-July 2019 | Existing policies not affected by results |
| 2019–2024 | Ban on use of genetic info for new life/TPD/income insurance (self-regulated) |
| Post-July 2024 | Government announced ban on genetic discrimination — not legislated as of March 2025 |
Medicare Eligibility for BRCA Testing
Eligible (MBS rebate) if ALL are met:
- High-risk personal or family history (e.g. based on eviQ)
- Testing requested by a public familial cancer clinic or oncologist/genetics specialist
- Genetic counselling provided before and after testing
Not eligible (out-of-pocket) if:
- Low-risk family history
- Direct-to-consumer request or private specialist without public referral
- Curiosity testing or ancestry-only interest
- Retesting for VUS without new evidence
MBS Item Numbers (as of 2025)
| Item | Description | Eligibility |
|---|---|---|
| 73296 | BRCA1/2 or multigene panel testing | Meets clinical/genetic criteria (eviQ/familial clinic) |
| 73297 | Predictive testing in relatives | Known family mutation; first-degree relative aged ≥18 |