Breast cancer
Breast cancer and benign breast disease: pathology, receptors and treatment
Triple assessment, benign lumps, fat necrosis, DCIS, ductal versus lobular cancer, grade, receptors and HER2 therapy for FCPS Part 1. Each treatment choice is explained by the biology it targets.
Triple assessment
- Every breast lump gets clinical examination, imaging and tissue diagnosis; each is scored 1 (normal) to 5 (malignant), and any discordance means more tissue or excision.
- Imaging: ultrasound under 35–40 (dense breasts); mammography plus ultrasound over that age; MRI for lobular cancer, implants and high-risk screening.
- Tissue: core needle biopsy is preferred over FNAC because it shows invasion and gives receptor status.
Benign breast conditions
| Condition | Typical patient and clue | Management |
|---|---|---|
| Fibroadenoma | Commonest lump under 25; smooth, painless, very mobile; not a precursor of cancer | Reassure after triple assessment; excise if over 3–4 cm or growing |
| Phyllodes tumour | 40s–50s, rapidly growing, leaf-like stroma | Wide local excision with clear margins (recurs otherwise) |
| Cyst | Perimenopausal; smooth, fluctuant | Aspirate; investigate if bloodstained or a mass remains |
| Duct ectasia | Older smokers; cheesy green discharge, slit-like nipple retraction | Reassure; excise ducts if troublesome |
| Intraductal papilloma | Bloody discharge from a single duct | Microdochectomy |
| Fat necrosis | After trauma (seat belt), surgery or radiotherapy | See below |
| Lactational abscess | *Staphylococcus aureus* | Aspiration, antibiotics, keep feeding or expressing |
- Fat necrosis mimics cancer: a firm, irregular, sometimes tender lump with skin tethering and coarse calcification on mammography. Damaged fat cells release lipid, which lipases split into fatty acids that bind calcium (saponification); macrophages fill with fat (foamy macrophages) and multinucleated foreign-body giant cells gather, followed by fibrosis that tethers the skin. Biopsy is needed because only about half of patients remember an injury.
- Gynaecomastia in men: puberty, spironolactone, digoxin, cimetidine, cirrhosis, hypogonadism, hCG-secreting testicular tumours.
Risk factors and genes
- Oestrogen exposure drives most risk: early menarche, late menopause, nulliparity, first pregnancy after 30, not breastfeeding, combined HRT, postmenopausal obesity (aromatase in fat makes oestrogen), alcohol.
- Others: age, atypical hyperplasia, LCIS, dense breasts, chest wall irradiation (Hodgkin mantle field), previous breast cancer.
| Gene | Chromosome | Associated cancers |
|---|---|---|
| BRCA1 | 17q | Breast (often triple negative, medullary-like), ovary |
| BRCA2 | 13q | Breast including male breast, ovary, prostate, pancreas |
| TP53 | 17p | Li–Fraumeni (sarcoma, brain, adrenal, breast) |
| PTEN; CDH1 | 10q; 16q | Cowden; lobular breast and diffuse gastric cancer |
- A young woman whose mother and sister died of breast cancer before 40 most likely carries BRCA1 (or BRCA2). Carriers have annual MRI from 30, and risk-reducing mastectomy and salpingo-oophorectomy are offered.
Pathology
- DCIS: malignant cells confined inside ducts with an intact myoepithelial layer. In high-grade (comedo) DCIS the centre of each duct becomes necrotic, and this necrotic debris calcifies, producing linear, branching microcalcifications in a segmental pattern on screening mammograms. It is excised even without a lump because untreated high-grade DCIS often becomes invasive. Paget disease of the nipple (eczema-like nipple) signals underlying DCIS or invasive cancer.
- LCIS: usually incidental, E-cadherin negative, a marker of risk in both breasts.
| Invasive type | Share | Features |
|---|---|---|
| Ductal (no special type) | 75–80% | Hard, gritty, stellate |
| Lobular | 10–15% | Single-file cells, E-cadherin loss, bilateral and multicentric, hard to see on mammography; spreads to peritoneum, ovary, GI tract |
| Medullary pattern | Rare | BRCA1, lymphocytes, triple negative |
| Mucinous, tubular | Older women | Good prognosis |
| Inflammatory | Rare | Peau d'orange and erythema from tumour in dermal lymphatics; neoadjuvant chemotherapy first |
- Skin puckering or dimpling occurs when tumour infiltrates and shortens the suspensory (Cooper) ligaments; peau d'orange is lymphatic obstruction with skin oedema around tethered hair follicles.
- Nottingham (modified Bloom–Richardson) grade scores three features from 1 to 3: tubule (gland) formation, nuclear pleomorphism and mitotic count. A total of 3–5 is grade 1, 6–7 grade 2, 8–9 grade 3. Grade describes how abnormal the cells look; stage describes how far it has spread. A small tumour can be grade 3.
Spread, staging and prognosis
- Commonest site: upper outer quadrant (most tissue). About 75% of lymph drains to the axillary nodes; medial tumours also drain to internal mammary nodes.
- Bone is the commonest distant site, especially vertebrae, reached through the valveless vertebral venous plexus via intercostal veins. Lung, liver, brain and pleura follow.
- Axillary node status is the most important prognostic factor. Four to nine positive axillary nodes is N2; a 6 cm tumour with skin involvement is T4, which makes it stage III. Nottingham Prognostic Index = 0.2 × size (cm) + grade + nodal score.
Receptors and systemic treatment
- ER and PR positive (70–80%): hormone therapy, better prognosis.
- Tamoxifen (a SERM) blocks the oestrogen receptor in breast tissue and works whatever the source of oestrogen, so it suits premenopausal women; side effects include VTE, endometrial cancer and hot flushes.
- Aromatase inhibitors (anastrozole, letrozole) block conversion of androgens to oestrogen in fat. After menopause that is the main source, but in a premenopausal woman the ovaries keep making oestrogen, and falling oestrogen raises gonadotrophins that stimulate the ovary further. An aromatase inhibitor alone is therefore inappropriate unless the ovaries are suppressed or menopause is confirmed (chemotherapy may stop periods only temporarily). Side effects: osteoporosis, arthralgia.
- Raloxifene reduces breast cancer risk in high-risk postmenopausal women and also protects bone.
- HER2 positive (15–20%, gene amplification): trastuzumab, a monoclonal antibody against HER2. HER2 signalling also protects cardiac myocytes, so trastuzumab can cause reversible cardiomyopathy; monitor ejection fraction by echocardiography before and during treatment, and take extra care with anthracyclines.
- Triple negative: young women, BRCA1, aggressive; chemotherapy, PARP inhibitors in BRCA carriers, immunotherapy.
Local treatment
- Breast-conserving surgery plus radiotherapy gives the same survival as mastectomy for suitable tumours. Mastectomy for large or multicentric tumours, or when radiotherapy is not possible.
- Sentinel node biopsy (blue dye and isotope) stages a clinically and ultrasound node-negative axilla; positive disease needs axillary clearance or radiotherapy.
- Clearance complications: lymphoedema, seroma, intercostobrachial nerve numbness of the medial upper arm, and long thoracic nerve injury causing winging of the scapula and loss of overhead abduction (serratus anterior cannot rotate the scapula).
Remember Tamoxifen blocks the receptor; aromatase inhibitors cut the supply, and only work when the ovaries are quiet.
Exam trap Never give an aromatase inhibitor alone to a woman who is still menstruating.
Exam trap Fat necrosis mimics carcinoma clinically and on mammography; biopsy settles it.
How FCPS asks about this
- HER2-positive, ER-negative cancer: trastuzumab; monitor cardiac function by echocardiography.
- Lump after seat-belt injury with foamy macrophages and giant cells: traumatic fat necrosis.
- Anastrozole in a 38-year-old with periods: inappropriate because her ovaries keep making oestrogen; tamoxifen is the drug for premenopausal women.
- Linear branching microcalcifications: calcified necrotic debris in high-grade comedo DCIS.
- Nottingham grade components: tubule formation, nuclear pleomorphism, mitotic count.
- Mother and sister with breast cancer before 40: BRCA1 on chromosome 17; lobular cancer loses E-cadherin.
- Winged scapula after axillary clearance: long thoracic nerve; axillary node status is the strongest prognostic factor.
Test yourself on this topic
5 of the 31 questions in our bank on this topic. Choose an answer to see why every option is right or wrong.
A breast cancer pathology report gives a Nottingham (modified Bloom-Richardson) grade of 3. Which of the following features are scored to give this grade?
Answer: Tubules, nuclear pleomorphism, mitoses
The Nottingham grade scores three features from 1 to 3: tubule (gland) formation, nuclear pleomorphism and mitotic count. The total of 3–9 gives grade 1 (3–5), grade 2 (6–7) or grade 3 (8–9). Grade reflects how differentiated and how actively dividing the tumour is. It is combined with size and node status in the Nottingham Prognostic Index, while TNM describes stage and receptor status guides systemic therapy.
Nottingham grade
- Tubule formation
- Nuclear pleomorphism
- Mitotic count
- Total 8–9: grade 3
Remember Breast grade: tubules, nuclei, mitoses.
Exam trap Grade and stage are different: a small tumour can be grade 3, and a large one grade 1.
Why the other options are wrong
- Size, nodes and metastases These are TNM stage elements.
- ER, PR and HER2 status Receptor status guides treatment but is not grade.
- Margins, vascular invasion and size These describe the excision, not the grade.
- Age, menopause and family history Clinical factors, not histological grade.
A 35-year-old woman with a germline BRCA1 mutation develops a high-grade breast cancer. Which receptor profile is it most likely to have?
Answer: ER, PR and HER2 all negative
BRCA1 is needed for homologous recombination repair of double-strand DNA breaks. Breast cancers in BRCA1 carriers are usually high-grade, basal-like tumours that lack oestrogen, progesterone and HER2 receptors (triple-negative). They do not respond to endocrine or anti-HER2 therapy but are sensitive to DNA-damaging chemotherapy and to PARP inhibitors, which exploit the repair defect. BRCA2 cancers are more often ER-positive.
BRCA1 tumours
- Defective homologous recombination
- Usually triple-negative, basal-like
- High grade, young women
- Sensitive to PARP inhibitors
Remember BRCA1 cancers are usually triple-negative.
Exam trap Young women with triple-negative breast cancer should be offered BRCA testing.
Why the other options are wrong
- ER and PR positive, HER2 negative More typical of BRCA2 and sporadic cancers.
- HER2 amplified, ER negative Uncommon in BRCA1 carriers.
- ER positive, HER2 positive Uncommon in BRCA1 carriers.
- PR positive only Rare and not linked to BRCA1.
Which part of the breast extends through the deep fascia into the axilla and is often missed on examination?
Answer: Axillary tail of Spence
The axillary tail (of Spence) is breast tissue running from the upper outer quadrant into the axilla through an opening in the deep fascia. The upper outer quadrant, including the tail, contains the most glandular tissue and is the commonest site of breast cancer, so the axilla must be examined with the breast.
Axillary tail
- Upper outer quadrant into axilla
- Pierces the deep fascia
- Most glandular tissue: upper outer
- Commonest cancer site
Remember Examine the axilla: the breast goes there too.
Exam trap The retromammary space lets a benign breast move freely over the chest wall.
Why the other options are wrong
- Retromammary space Loose tissue behind the breast, over pectoralis fascia.
- Areola Pigmented skin around the nipple.
- Ligaments of Cooper Fibrous bands to the skin.
- Lactiferous sinus Dilated duct under the areola.
A 38-year-old woman with regular periods and oestrogen receptor-positive breast cancer is started on anastrozole alone after surgery. Why is this treatment inappropriate?
Answer: Her ovaries keep making oestrogen
After the menopause, oestrogen comes mainly from aromatisation of androgens in fat and other tissues, and aromatase inhibitors block this. Before the menopause, most oestrogen comes from the ovaries. Lowering oestrogen with an aromatase inhibitor reduces negative feedback, so FSH and LH rise and stimulate the ovaries further. Premenopausal women need tamoxifen, or an aromatase inhibitor only with ovarian suppression (for example a GnRH agonist).
Aromatase inhibitors
- Block peripheral aromatisation
- Work in postmenopausal women
- Premenopausal: ovaries escape via FSH/LH
- Use with ovarian suppression if young
Remember Aromatase inhibitor alone is for postmenopausal women.
Exam trap Chemotherapy can stop periods temporarily; ovarian function may return, so menopause must be confirmed before AI alone.
Why the other options are wrong
- Anastrozole blocks the receptor Anastrozole inhibits aromatase; it does not block the receptor.
- She has no aromatase enzyme Aromatase is present in ovaries and peripheral tissues at all ages.
- It acts only on HER2 tumours Anti-HER2 drugs are different.
- It causes endometrial cancer Tamoxifen, not anastrozole, raises endometrial cancer risk.
A 55-year-old man has a hard, painless lump beneath the nipple with skin tethering and a little bloody discharge. Core biopsy shows invasive ductal carcinoma. Which of the following germline mutations most increases the risk of this cancer?
Answer: BRCA2
Male breast cancer is uncommon, but its strongest inherited risk factor is a germline BRCA2 mutation, which raises a man's lifetime risk many-fold; BRCA1 raises it much less. Other risks are Klinefelter syndrome, high oestrogen states such as cirrhosis, and chest wall radiation. Most male breast cancers are invasive ductal and oestrogen receptor-positive. A man with breast cancer should be offered genetic testing, because relatives may carry the mutation.
Male breast cancer
- Strongest gene: BRCA2
- Also Klinefelter, high oestrogen
- Usually ductal, ER-positive
- Offer genetic testing
Remember Breast cancer in a man: think BRCA2.
Exam trap A hard, eccentric subareolar lump in a man is not gynaecomastia until examined and biopsied.
Why the other options are wrong
- BRCA1 Raises male risk far less than BRCA2.
- TP53 (Li-Fraumeni) Causes many cancers at young ages, but male breast cancer is not its hallmark.
- PTEN (Cowden) Mainly female breast, thyroid and endometrial cancer.
- CDH1 Linked to lobular breast and diffuse gastric cancer in women.
Where this sits in the CPSP syllabus
- Surgery & Allied, Paper 2: Oncology, Breast cancer
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