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.
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 | Largest group; often older women | PIK3CA, 16q loss; luminal A and B | Bone metastases, late relapse; endocrine therapy |
| HER2-positive | A minority; any age | ERBB2 amplification | High grade, brain metastases; anti-HER2 therapy |
| Triple-negative | 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.
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.
Elsewhere in DurgiPedia
Connections
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 (National Cancer Institute, 2026); Breast cancer: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.