[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/) › Sporadic breast cancer: molecular subtypes # Sporadic breast cancer: molecular subtypes - Mechanism Most breast cancers are not inherited. They fall into three groups by their receptors, and each group grows, spreads and responds to treatment differently. Updated Nov 12, 2026 ## Key points - ER-positive, HER2-negative: the majority; older women; PIK3CA mutations; precursors flat epithelial atypia, atypical ductal hyperplasia and low-grade DCIS; late recurrences; endocrine therapy. - Luminal A (low proliferation, best prognosis) vs luminal B (higher proliferation, some HER2-positive). - HER2-positive: ERBB2 amplification on 17q; high grade; brain metastases more common; targeted anti-HER2 therapy transformed the prognosis. - Triple-negative: TP53 mutations, basal-like (CK5/6, EGFR), BRCA1-like; younger women and women of African ancestry; early visceral and brain recurrences. - Genetic changes in the low-grade pathway: 16q loss, 1q gain; in high-grade pathways: TP53, complex copy-number changes. ## What it is Most breast cancers are sporadic and are driven by hormone exposure and acquired mutations. They divide into three major groups according to estrogen receptor (ER) and HER2 status. ER-positive, HER2-negative cancers are the largest group, often low to intermediate grade, and arise through a low-grade pathway with PIK3CA mutations. HER2-positive cancers have amplified ERBB2 and grow aggressively but respond to HER2-targeted drugs. Triple-negative cancers, lacking ER, PR and HER2, are mostly basal-like with TP53 mutations and early recurrence. Gene-expression profiling describes overlapping intrinsic subtypes. ## Step by step - Repeated cycles of estrogen and progesterone stimulate breast epithelium to divide. - Mutations accumulate in luminal or progenitor cells (PIK3CA in ER-positive, TP53 in high-grade tumours). - In some clones, ERBB2 becomes amplified and HER2 signalling drives growth. - Clones progress through precursor lesions to carcinoma in situ and then invasion. - The receptor profile of the final tumour decides its behaviour and its targeted treatments. ## The three major groups of invasive breast cancer | Group | Share and patient | Biology | Behaviour and treatment target | | --- | --- | --- | --- | | [ER-positive, HER2-negative](https://durgical.com/en/conditions/breast-cancer/) | Largest group; often older women | PIK3CA, 16q loss; luminal A and B | Bone metastases, late relapse; endocrine therapy | | [HER2-positive](https://durgical.com/en/conditions/breast-cancer/) | A minority; any age | ERBB2 amplification | High grade, brain metastases; anti-HER2 therapy | | [Triple-negative](https://durgical.com/en/conditions/breast-cancer/) | A minority; younger women, BRCA1 carriers | TP53, basal-like | Early visceral and brain relapse; chemotherapy, immunotherapy in some | ## Markers - ER and PR (nuclear immunostain) - HER2 (immunostain and in situ hybridisation) - Ki-67 - CK5/6 and EGFR (basal-like) ## Clinical notes - Every invasive breast carcinoma is tested for ER, PR and HER2 because these results choose the treatment. - ER-positive cancers can recur ten or more years after diagnosis; triple-negative cancers relapse mostly in the first years. ## Memory aid Three doors to treatment: the estrogen door, the HER2 door, and the triple-negative room with no door, where chemotherapy is the key. ## Test yourself Think of the answer, then tap the question to see it. ## What are the three major groups of breast cancer by receptor status? ER-positive HER2-negative, HER2-positive, and triple-negative (ER, PR and HER2 negative). ## Which gene is amplified in HER2-positive breast cancer? ERBB2, on chromosome 17q. ## Which group is typical of BRCA1 carriers? Triple-negative, basal-like cancer with TP53 mutation. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/sporadic-breast-cancer-molecular-subtypes/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Nuclear receptors](https://durgical.com/en/biochemistry/topics/nuclear-receptors/) - [Receptor tyrosine kinases](https://durgical.com/en/biochemistry/topics/receptor-tyrosine-kinases/) - [Oncogenes and tumour suppressor genes](https://durgical.com/en/biochemistry/topics/oncogenes-and-tumour-suppressor-genes/) ## Connections ## Related 8 - [Familial breast cancer: BRCA1, BRCA2 and others](https://durgical.com/en/general-pathology/familial-breast-cancer-brca1-brca2-and-others/) - [Invasive breast carcinoma of no special type](https://durgical.com/en/general-pathology/invasive-breast-carcinoma-of-no-special-type/) - [Breast cancer: prognostic factors and staging](https://durgical.com/en/general-pathology/breast-cancer-prognostic-factors-and-staging/) - [Atypical breast hyperplasia and cancer risk](https://durgical.com/en/general-pathology/atypical-breast-hyperplasia-and-cancer-risk/) - [Ductal carcinoma in situ and Paget disease of the nipple](https://durgical.com/en/general-pathology/ductal-carcinoma-in-situ-and-paget-disease-of-the-nipple/) - [Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know](https://durgical.com/en/general-pathology/oncogenes-ras-myc-her2-bcr-abl-and-the-table-to-know/) - [Multistep carcinogenesis: the adenoma–carcinoma sequence](https://durgical.com/en/general-pathology/multistep-carcinogenesis-the-adenoma-carcinoma-sequence/) - [Translocations, amplifications and epigenetic changes in cancer](https://durgical.com/en/general-pathology/translocations-amplifications-and-epigenetic-changes-in-cancer/) ## Related conditions 2 - [Breast cancer](https://durgical.com/en/conditions/breast-cancer/) - [Hereditary breast and ovarian cancer syndrome (BRCA1/BRCA2)](https://durgical.com/en/conditions/hereditary-breast-and-ovarian-cancer-syndrome/) [← 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: [Breast Cancer Treatment (PDQ®)–Health Professional Version](https://www.cancer.gov/types/breast/hp/breast-treatment-pdq) (National Cancer Institute, 2026); [Breast cancer: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/breast-cancer/) (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/sporadic-breast-cancer-molecular-subtypes/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/sporadic-breast-cancer-molecular-subtypes/