[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Breast](https://durgical.com/en/general-pathology/areas/breast/) › Familial breast cancer: BRCA1, BRCA2 and others # Familial breast cancer: BRCA1, BRCA2 and others - Mechanism A minority of breast cancers come from an inherited faulty gene, most often BRCA1 or BRCA2; they start younger, can affect both breasts and run in families. Updated Nov 12, 2026 ## Key points - Clues to a hereditary cause: young age at diagnosis, bilateral or multiple primaries, male breast cancer, ovarian cancer in the family, several affected relatives, triple-negative cancer in a young woman. - BRCA1 (chromosome 17q21): high lifetime risk of breast and ovarian cancer; tumours are often triple-negative, basal-like, high grade, with medullary features. - BRCA2 (chromosome 13q12): breast (including male), ovarian, prostate and pancreatic cancer and melanoma; tumours usually ER-positive. - TP53 (Li-Fraumeni): very early breast cancer, often HER2-positive, with sarcomas, brain and adrenal tumours. - PTEN (Cowden): breast, thyroid and endometrial cancer and hamartomas; CDH1: lobular breast cancer and diffuse gastric cancer. - BRCA-deficient cancers are sensitive to platinum and PARP inhibitors (synthetic lethality). ## What it is About one in ten breast cancers is caused by an inherited mutation in a single gene. BRCA1 and BRCA2, which repair DNA double-strand breaks by homologous recombination, account for the largest share; carriers inherit one faulty copy, and tumours arise when the second copy is lost. Other high-risk genes are TP53 (Li-Fraumeni syndrome), PTEN (Cowden syndrome), CDH1 (hereditary diffuse gastric cancer with lobular breast cancer), STK11 and PALB2, while CHEK2 and ATM add moderate risk. BRCA1 cancers are usually triple-negative and basal-like; BRCA2 cancers are usually ER-positive. ## Step by step - A person inherits one mutated copy of a DNA repair gene such as BRCA1 or BRCA2 (first hit, in every cell). - In a breast epithelial cell, the normal copy is lost (second hit). - Without homologous recombination, double-strand breaks are repaired by error-prone pathways. - Genomic instability accumulates, often with TP53 loss, and a cancer develops at a younger age than usual. - Because every cell carries the first hit, both breasts and other organs (ovary, prostate, pancreas) are at risk. ## High- and moderate-risk breast cancer genes | Gene | Syndrome | Other cancers | Typical breast tumour | | --- | --- | --- | --- | | [BRCA1](https://durgical.com/en/conditions/hereditary-breast-and-ovarian-cancer-syndrome/) | Hereditary breast and ovarian cancer | Ovary, tube | Triple-negative, basal-like | | [BRCA2](https://durgical.com/en/conditions/hereditary-breast-and-ovarian-cancer-syndrome/) | Hereditary breast and ovarian cancer | Ovary, male breast, prostate, pancreas, melanoma | ER-positive | | TP53 | Li-Fraumeni syndrome | Sarcoma, brain, adrenal cortex, leukaemia | Very early onset, often HER2-positive | | PTEN | Cowden syndrome | Thyroid, endometrium, hamartomas | Variable | | [CDH1](https://durgical.com/en/conditions/gastric-cancer/) | Hereditary diffuse gastric cancer | Diffuse (signet-ring) gastric cancer | Invasive lobular carcinoma | | PALB2, CHEK2, ATM | No single named syndrome | Pancreas (PALB2), others | Mostly ER-positive | ## Clinical notes - Genetic counselling and testing are offered to patients and families with suggestive histories; testing a patient's tumour can also reveal a germline mutation. - Carriers are offered intensified screening with MRI and risk-reducing mastectomy or salpingo-oophorectomy. - Founder BRCA mutations have been described in some Colombian and Hispanic populations, which makes family history especially informative. ## Memory aid BRCA1 is basal and bad-tempered (triple-negative); BRCA2 brings company: men, prostate and pancreas, and stays ER-positive. ## Test yourself Think of the answer, then tap the question to see it. ## What do BRCA1 and BRCA2 normally do? They repair DNA double-strand breaks by homologous recombination. ## Which BRCA gene is linked to male breast cancer and usually ER-positive tumours? BRCA2. ## Which germline gene causes lobular breast cancer together with diffuse gastric cancer? CDH1, which encodes E-cadherin. ## Why do BRCA-deficient cancers respond to PARP inhibitors? Blocking PARP adds a second repair defect to the homologous recombination defect, and the combined loss kills the tumour cells (synthetic lethality). [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/familial-breast-cancer-brca1-brca2-and-others/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Oncogenes and tumour suppressor genes](https://durgical.com/en/biochemistry/topics/oncogenes-and-tumour-suppressor-genes/) ## Connections ## Related 9 - [Breast cancer: risk factors](https://durgical.com/en/general-pathology/breast-cancer-risk-factors/) - [Sporadic breast cancer: molecular subtypes](https://durgical.com/en/general-pathology/sporadic-breast-cancer-molecular-subtypes/) - [The male breast: gynecomastia and male breast cancer](https://durgical.com/en/general-pathology/the-male-breast-gynecomastia-and-male-breast-cancer/) - [Lobular carcinoma in situ](https://durgical.com/en/general-pathology/lobular-carcinoma-in-situ/) - [High-grade serous carcinoma](https://durgical.com/en/general-pathology/high-grade-serous-carcinoma/) - [Prostate cancer: pathogenesis](https://durgical.com/en/general-pathology/prostate-cancer-pathogenesis/) - [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/) - [Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum](https://durgical.com/en/general-pathology/genomic-instability-mismatch-repair-brca-and-xeroderma-pigmentosum/) - [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/) ## Related conditions 6 - [Hereditary breast and ovarian cancer syndrome (BRCA1/BRCA2)](https://durgical.com/en/conditions/hereditary-breast-and-ovarian-cancer-syndrome/) - [Breast cancer](https://durgical.com/en/conditions/breast-cancer/) - [Ovarian cancer](https://durgical.com/en/conditions/ovarian-cancer/) - [Prostate cancer](https://durgical.com/en/conditions/prostate-cancer/) - [Gastric cancer](https://durgical.com/en/conditions/gastric-cancer/) - [Melanoma](https://durgical.com/en/conditions/melanoma/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [Genetics of Breast and Gynecologic Cancers (PDQ®)–Health Professional Version](https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq) (National Cancer Institute, 2026); [BRCA1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/brca1/) (MedlinePlus, US National Library of Medicine, 2026); [BRCA2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/brca2/) (MedlinePlus, US National Library of Medicine, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/familial-breast-cancer-brca1-brca2-and-others/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/familial-breast-cancer-brca1-brca2-and-others/