Breast tumours
How breast carcinoma arises from luminal cells of the lobule, why DCIS and lobular neoplasia precede ductal and lobular invasion, what oestrogen receptor, PR and HER2 status say about its biology, and how it spreads.
By the end, you can
- Relate the cells of the breast to its benign, in situ and invasive tumours, and name the main types in current terminology.
- Explain how lifetime oestrogen exposure and inherited BRCA1 or BRCA2 variants raise the risk of breast carcinoma.
- Contrast DCIS with lobular neoplasia, and invasive carcinoma of no special type with invasive lobular carcinoma, linking E-cadherin loss to single-file growth.
- Describe oestrogen receptor, progesterone receptor and HER2 status as biology, as the basis of the molecular subtypes and as predictive factors.
- Explain how breast carcinoma spreads, what grade and stage measure, and why it causes skin dimpling, nipple retraction and orange-peel skin.
What it is
Breast tumours arise from the epithelium of the terminal duct lobular unit or, less often, its stroma. Almost all malignant ones are carcinomas of the luminal epithelium: confined within ducts and lobules as carcinoma in situ, or invasive once they cross the basement membrane. Invasive carcinoma is classified by its pattern (no special type, lobular, special types) and by its oestrogen receptor (ER), progesterone receptor (PR) and HER2 status.
6 types to tell apart
- Ductal carcinoma in situ (DCIS)
- Malignant, clonal luminal cells filling and distending ducts within an intact basement membrane; graded low, intermediate or high; a non-obligate precursor of invasive carcinoma.
- Lobular neoplasia (ALH and LCIS)
- Small, discohesive cells without E-cadherin filling lobular acini; usually found by chance, a marker of risk in both breasts and a non-obligate precursor of lobular carcinoma.
- Invasive carcinoma of no special type (NST)
- The commonest invasive type, about three-quarters of cases; formerly called invasive ductal carcinoma. Nests, cords and glands in a dense fibrous stroma.
- Invasive lobular carcinoma
- About a tenth of cases: E-cadherin-negative cells infiltrating singly and in single file, often forming no discrete mass; usually ER positive.
- Special types
- Tubular and mucinous carcinomas, usually low grade with a favourable course; metaplastic carcinoma, usually triple negative and aggressive; NST with medullary pattern, rich in lymphocytes.
- Non-epithelial tumours
- Malignant phyllodes tumour, angiosarcoma (rare, sometimes years after radiotherapy) and lymphoma; they behave like their counterparts elsewhere.
US spelling: tumours → tumors, oestrogen → estrogen.
Normal function
The cells of the breast and the signals they obey
The of the breast drain through to the . Their working units are terminal duct lobular units, lined by inner luminal cells and outer myoepithelial cells on a basement membrane, in a hormone-responsive stroma (the benign changes lesson covers them in detail).
Some luminal cells carry the oestrogen receptor (ER), a nuclear receptor: oestrogen binds it and it switches on growth genes, including the gene for the progesterone receptor (PR), so PR expression shows a working ER pathway. HER2 is a membrane tyrosine kinase receptor of the EGFR family; normal cells carry few copies, and it signals only by pairing with its partners. BRCA1 and BRCA2 repair DNA double-strand breaks accurately by homologous recombination.
About three-quarters of the lymph from the breast drains to the axillary lymph nodes, along the of the gland towards the armpit; the rest goes mainly to nodes beside the sternum.
| Feature | Benign or risk lesion | In situ | Invasive |
|---|---|---|---|
| Ductal (luminal) epithelium | Usual and atypical ductal hyperplasia | DCIS | Invasive carcinoma NST |
| Lobular epithelium | Atypical lobular hyperplasia | Lobular carcinoma in situ | Invasive lobular carcinoma |
| Special patterns | Not applicable | Not applicable | Tubular, mucinous, metaplastic carcinoma |
| Lobular stroma | Fibroadenoma; benign phyllodes | Not applicable | Malignant phyllodes tumour |
| Vessels and lymphoid tissue | Haemangioma | Not applicable | Angiosarcoma; lymphoma |
Simplified from the WHO classification (5th edition). "Ductal" and "lobular" describe patterns, not the site of origin: both arise in the terminal duct lobular unit.
Underlying change · Step 1 of 5
Why it develops: oestrogen exposure and inherited genes
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 9 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 2 of 5
Carcinoma in situ: DCIS and lobular neoplasia
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 9 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 5
Invasive carcinoma: no special type and lobular
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 9 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
Hormone receptors, HER2 and the molecular subtypes
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 9 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Local growth, spread and stage
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 9 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 9 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 9 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 9 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .