Synopsis
Recognise inherited breast-cancer patterns, distinguish germline from tumour-only findings, select the most informative person for testing, and explain family and treatment consequences clearly.
- Constitutional pathogenic variants are present throughout the body and can affect cancer risk, treatment and relatives; somatic variants are confined to tumour cells and are not automatically heritable.
- BRCA1 and BRCA2 encode proteins central to homologous-recombination DNA repair. PALB2 is another high-risk breast gene; TP53, PTEN, STK11 and CDH1 occur in broader cancer-predisposition syndromes.
- CHEK2, ATM, RAD51C and RAD51D can confer moderate or variant-specific breast risk. Management follows the exact gene, variant classification, family history, age and current NHS pathway.
Reasoning priorities
Define which people and cancers make inherited predisposition plausible and identify the most informative living relative.
Record maternal and paternal lineages, exact primary sites, ages, bilateral disease and existing laboratory reports. Small families and adoption limit reassurance.
Worked reasoning
Illustrative worked example: an unaffected 35-year-old asks about inherited risk after ovarian cancer in her mother and breast cancer at 39 in a living, previously untested maternal aunt.
- Genetics verified the diagnoses and pedigree, obtained consent and arranged testing of the affected aunt first because her result offered the most informative route to a familial explanation.
- The aunt's constitutional laboratory report identified a pathogenic BRCA2 variant. With the aunt's agreement, the family received a written communication explaining the result and how relatives could access counselling.
- After counselling about possible results, psychological and reproductive implications, the unaffected patient chose targeted predictive testing for that exact familial variant rather than an unexplained broad panel.
- Her non-tumour sample tested positive for the familial BRCA2 variant. The clinician communicated the confirmed carrier result, checked understanding and arranged a gene-specific breast surveillance and risk-reduction consultation through the local genetics/breast service.
- At the subsequent appointment, the signed reports and referral were present, her surveillance plan had been agreed and she had received written contact details for relatives. She chose surveillance while considering preventive options, demonstrating an observed informed decision rather than an assumed obligation to undergo surgery.