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Breast cancer – a summary

  • A common and important disease
  • A useful model of neoplastic progression
  • Differential diagnosis relates to age
  • Remember need for triple assessment
  • Stage and grade are important determinants of outcome

  • Arises in the internal duct lobular unit
  • Breast = modified sweat gland with deep fascia and fat
  • Common presentation of breast cancer = palpable mass
  • Histological typing relates to the presumed origin (lobular = from lobular epithelium; ductular = from the terminal ductular system; probably an oversimplification)

TDLU – terminal duct lobular unit

Normal Duct – Microscopic high power

  • Tumours arise from the secretory epithelial cells
  • Deep to the secretory layer are myoepithelial cells (have contractile properties; not breast cancer, can produce other cancer)

Epidemiology of breast cancer

  • Incidence
    • 4376 cancers in women (42 men)
    • 28% of all cancers in females Mortality
    • 905 deaths in women
    • 16% of all cancer deaths in females
  • Lifetime risk
    • 1 in 9 women will develop breast cancer by the age of 85 years
  • BreastScreen takes place between 50 and 70
  • In the 80s-90s, incidence of breast cancer increased due to better screening
  • Mortality has fallen because screening has improved, allowing early diagnosis and treatment


  • Increasing age
  • Hyper-oestrogenic states
    • Long reproductive phase (early menarche, late menopause)
    • Nulliparity, or first child >30, no or limited breast feeding
    • Obesity (postmenopausal women; because fatty tissue produces oestrogen)
    • Hormone replacement therapy, older forms of OCP
  • Other environmental factors
    • Excessive alcohol consumption
    • Radiation, ? Viruses
  • Hereditary factors
    • BRCA1 and BRCA2
      • (familial breast cancer = early age, bilateral, male breast cancer)
  • Just because someone has no family history of breast cancer doesn't mean they're not at risk

The pathogenesis of breast cancer

  • Hyperplasia is not a neoplastic process
    • Polyclonal process, recruitment of stem cells
    • Sets the scene that favours the development of neoplastic cells
  • DCIS = ductal carcinoma in situ
    • The tumour looks like a malignant cell, but has not yet invaded (but probably will if you leave it there)
    • Within this clone of cells, the capacity to invade will evolve, producing a cancer

Risk from preexisting breast lesions

  • Ductal hyperplasia (x1.5-2)
  • Atypical ductal hyperplasia (x4-5; a neoplasm)
  • DCIS – ipsilateral/recurrence risk
  • Previous cancer (x3-4)
  • Numbers shown are relative risk: the increased risk of getting breast cancer in people with the underlying condition compared to the risk in those without that condition)

Pathological typing of breast cancer

  • Non-invasive
    • Ductal carcinoma in situ (DCIS)
    • Lobular carcinoma in situ (LCIS)
  • Invasive
    • Invasive ductal carcinoma (80%) ("breast cancer")
    • Invasive lobular carcinoma (5%)
    • Other special types of invasive cancer (5-10%)
  • Paget’s disease of the nipple

Ductal carcinoma in situ

  • Proliferation of the cells , making a thicker ductular wall
  • Lumen filled with secretions and calcification in ducts; shows up on mammogram without palpable mass
  • Require management because, if left there, they'll progress to cancer

Breast carcinoma - macroscopic

  • Desmoplastic tissue around the cancer = hard, mobile lump

Invasive ductal carcinoma - microscopic low power

  • Blue = tumour
  • Induces a desmoplastic response around it, which is hard
  • Stellate scar is noted on mammogram - very distinctive of invasive carcinoma

Invasive ductal carcinoma - grade 1

  • Tumour cells look similar to normal ductal cells: well differentiated

Invasive ductal carcinoma - grade 3

  • Stop forming ducts, instead forming cords of cells; due to loss of differentiation
  • Less differentiated = higher grade = behaves worse = more likely to spread

Invasive Lobular Carcinoma - Microscopic

  • Actually arises from the same epithelium as ductal carcinomas, but the cells behave differently
  • Mass in the background = tumour cells of invasive lobular carcinoma
  • Form cords, wandering around the normal breast tissue
  • Actually has a better outcome than ductal
  • That's why we distinguish between ductal and lobular even though the site of origin is the same

Paget's disease of the nipple

  • Epidermal invasion from underlying in situ or invasive carcinoma
  • Tumour cells migrate upwards without going through blood
  • Produces a rash on the nipple; may be an early symptom

Clinical issues

  • Diagnostic features
    • What features on history or examination suggest cancer?
    • Could it be something else?
  • Risk factors
    • What is the risk profile for this person?
  • Prognostic factors
    • Is there evidence that the tumour has spread?
    • Locally?
    • To distant sites?
  • History
    • Breast lump
    • Abnormality on screening mammogram
    • Nipple discharge (uncommon)
    • Breast pain (uncommon)
  • Examination
    • Characteristics of mass (should be hard due to desmoplasia)
    • Signs of locally advanced disease (e.g. involve skin causing puckering or tethering)
      • Tethering/nipple retraction
      • Peau d’orange
    • Axillary lymphadenopathy (30% False Positive, 30% False Negative)

Clinical DDx of a breast lump

  • Carcinoma
  • Fibrocystic change (with prominent focal abnormality)
  • Fibroadenoma
  • Fat necrosis
  • Mastitis/breast abscess
  • Other benign tumours
  • Lots of other things

Note importance of age in framing DDx!

Fibrocystic change

  • Cysts +/- apocrine metaplasia
  • Fibrosis
  • Adenosis
  • Epithelial hyperplasia
  • Atypical epithelial hyperplasia (when there is significant epithelial hyperplasia associated with fibrocystic change, it increases risk; otherwise fibrocystic change is OK)

Fibroadenoma - Macroscopic

  • Proliferation of stroma, mixed with glands
  • Mobile, well circumscribed, firm/rubbery

Clinical features of breast cancer

  • Early breast cancer
    • Confined to the breast +/- axillary nodes
  • Locally advanced
    • Tumour >5cm And/Or
    • Evidence of spread to chest wall or skin
  • Nipple retraction: attachment of the tumour to secretory ducts, that it pulls on
  • Peau d'orange: oedema of the dermis because of the tumour blocking the lymphatics draining the skin. Then the skin becomes swollen except where the hair follicles are
    • This is a bad sign - means the disease is very locally advanced

Diagnosis of breast cancer

  • Diagnosis is by Triple Assessment
    • 1. Clinical Evaluation
    • 2. Imaging (ultrasound <35 years old or mammography >35 years old; due to changes in fat/lobule composition with age)
    • 3. Pathological examination of cells or tissues from the lesion

Imaging of a breast mass

  • Ultrasound
    • Best in younger women (denser breasts)
    • Best for cystic lesions
  • Mammogram
    • Better in older women (>35yo)
    • Note difference between mammogram as a diagnostic test and a screening test

Mammogram - stellate lesion

  • Might also be palpable
  • Doesn't show the tumour itself, but shows the desmoplasia due to it

DCIS - mammographic granular microcalcifications

DCIS - with necrosis and calcification

Getting cells or tissue from a breast mass

  • Fine needle aspirate :)
  • Core biopsy (including mammotome)
  • Excision biopsy
  • Intraoperative biopsy (Frozen section) :(

Breast Fine needle aspiration (FNA)

  • Simple, relatively painless, quick
  • Accuracy
    • False positives are rare
    • False negatives are relatively common
  • (remember that diagnosis is based on triple assessment)

Outcomes in breast cancer

  • Stage most important, then grade
  • Overall 5 year survival 88%.
  • Outcome for an individual is complex, and is influenced by
  1. Stage
  2. Grade
  3. Other pathological features
    1. Type, margins, lymphatic or vascular invasion
  4. Biological factors
    1. Oestrogen/Progesterone receptor status
    2. HER2/neu (erbB2) overexpression
  5. Host factors
    1. age, menopausal status, intercurrent illness

Staging of breast cancer

  • Tumour
    • Size, lymphatic invasion, involvement of adjacent structures
  • Nodes
    • Axillary sampling, axillary clearance, sentinel node biopsy
    • Number of involved nodes, extranodal spread
  • Metastases
    • Presence or absence of distant mets

  • Axillary clearance = remove all the lymph nodes; causes oedema in the area
  • Sentinel node biopsy, we use dye to determine which node is draining the breast, then remove that one for pathological analysis
  • More nodes and more distant spread = poorer survival

Grading of breast cancer

  • Grading in breast cancer is usually based on
    • Extent of tubule formation (more is good)
    • Number of mitotic figures (less is good)
    • Degree of nuclear pleomorphism (less is good)
  • Grade is closely related to the idea of differentiation
    • Grade 1 - well differentiated, best prognosis
    • Grade 3 - poorly differentiated, worst prognosis

Special stains - Her2/neu (erbB2)

  • “Predictive” marker - indicates likely response to treatment (special, expensive antibody therapy)

Breast cancer – a summary

  • A common and important disease
  • A useful model of neoplastic progression
  • Differential diagnosis relates to age
  • Remember need for triple assessment
  • Stage and grade are important determinants of outcome