Synopsis
Identify inherited breast-cancer risk from both sides of a family, test the most informative person, interpret pathogenic and uncertain variants correctly and coordinate gene-specific surveillance, prevention, treatment and cascade care.
- Take a three-generation history covering maternal and paternal relatives, cancer site, age at diagnosis, bilateral or multiple primaries, ancestry and confirmed pathology; small families and early deaths can hide inherited risk.
- Test an affected relative first whenever possible because a negative result in an unaffected person is often uninformative when the familial cause is unknown.
- Use an accredited germline multigene panel matched to the phenotype rather than ordering BRCA1 and BRCA2 reflexively for every family or using a consumer test.
- Pathogenic and likely pathogenic variants can guide care; a variant of uncertain significance is managed from personal and family risk until laboratory reclassification.
- BRCA1, BRCA2, PALB2, TP53, PTEN, CDH1 and STK11 are important high-risk contexts, while ATM and CHEK2 often confer moderate risk modified by family and polygenic background.
- First-line surveillance modality and start age are gene and risk specific. Younger high-risk patients commonly receive contrast MRI, with mammography added or substituted according to age, gene and radiation considerations.
- Risk-reducing bilateral mastectomy substantially reduces but does not abolish breast-cancer risk and requires multidisciplinary genetic, surgical, reconstructive and psychological counselling.
- Risk-reducing salpingo-oophorectomy is more effective than unproven routine ovarian screening for BRCA-associated ovarian risk; timing differs between genes and reproductive plans.
- Tamoxifen before menopause and anastrozole after menopause can reduce ER-positive breast cancer in selected high-risk people, but gene biology and treatment toxicity determine usefulness.
- A germline result may affect breast surgery, radiotherapy, ovarian prevention, systemic treatment and trials in a person who already has cancer, so referral should not be deferred until survivorship.
- Cascade testing is targeted to the known familial variant and requires consent and support; clinicians facilitate family communication but do not disclose one person’s result casually.
- Offer fertility and reproductive counselling, including prenatal and preimplantation options, before risk-reducing surgery or gonadotoxic treatment narrows choice.
Key red flags
Breast cancer at a young age, bilateral primaries, male breast cancer or breast and ovarian cancer in one lineage suggests inherited susceptibility.
Ovarian, pancreatic, metastatic or high-risk prostate cancer alongside breast cancer can be part of a BRCA-related family pattern.
Sarcoma, brain tumour, adrenocortical cancer and very early breast cancer in a family raises TP53-associated Li–Fraumeni syndrome.
Diffuse gastric cancer with lobular breast cancer raises CDH1-associated hereditary diffuse gastric cancer and needs specialist gene-specific management.
A variant of uncertain significance must not drive irreversible surgery or predictive testing of healthy relatives.
New symptoms in a mutation carrier require diagnostic imaging even when a recent surveillance MRI or mammogram was normal.
A mutation carrier with a new lump enters urgent triple assessment; surveillance imaging is not a substitute for symptomatic diagnosis.
Investigation priorities
Identify syndromic patterns, the most informative person to test and relatives who may benefit from cascade care.
Detect preclinical breast cancer at the interval and with the modality appropriate to current absolute risk.
Management branches
Personal or family cancer features suggest inherited breast-cancer susceptibility.
- Collect cancers, ages, bilateral and multiple primaries, ancestry and both parental lineages and verify key pathology or death records where feasible.
- Use current genomic-testing criteria and a validated risk model to determine genetics referral and identify the most informative living affected relative.
- Provide pre-test counselling on possible positive, negative, uncertain and incidental results, data use, family implications and the limits of insurance or direct-to-consumer tests.