Breast Cancer: Secondary Care

Question 1

What does a normal breast tissue look like histologically?

Answer 1

Modified sweat glands.
Non-functional except during lactation.
Lobules= acini and intralobular stroma.

Question 2

What physiological changes are seen in breast tissue?

Answer 2

1. Prepubertal breasts show few lobules.
2. Menarche show increase in number of lobules and increased volume of interlobular stroma.
3. Menstrual cycle: follicular phase lobules quiescent, after ovulation cell proliferation and stromal oedema, with menstruation see decrease in size of lobules.
4. Pregnancy: increase in size and number of lobules, decrease in stroma, secretory changes.
5. Cessation of lactation: atrophy of lobules but not to former levels.
6. Age: terminal duct lobular units decrease in number and size. Interlobular stroma replaced by adipose tissue (mammograms easier).

Question 3

How can breast conditions present?

Answer 3

1. Pain.
2. Palpable mass.
3. Nipple discharge.
4. Skin changes.
5. Lumpiness.
6. Mammographic abnormalities.

Question 4

Which breast conditions cause pain?

Answer 4

1. Cyclical and diffuse (physiological).
2. Non-cyclical and focus: ruptured cysts, injury and inflammation.
3. Breast cancer.

Question 5

Which breast conditions cause a palpable mass?

Answer 5

1. Normal nodularity.
2. Invasive carcinomas.
3. Fibroadenomas.
4. Cysts.

Question 6

When are palpable masses in the breast worrying?

Answer 6

If hard, craggy and fixed.

Question 7

What conditions cause nipple discharge?

Answer 7

1. Milky: endocrine (pituitary adenoma, side effect of drug).
2. Bloody/serous: benign lesions such as papilloma, duct ectasia or more concerning if unilateral.

Question 8

Which breast conditions cause mammographic abnormalities that are worrying?

Answer 8

Densities: invasive carcinoma in situ, cysts.
Calcification: ductal carcinoma in situ and benign changes.

Question 9

When is screening for breast cancer conducted one women?

Answer 9

Every 3 years from the age of 47 to 73 years old.

Easier to detect lesion in breasts of older women.

Question 10

Are breast conditions common?

Answer 10

Yes. Most breast symptoms and signs are benign.
Fibroadenomas are the most common benign tumour.
Breast cancer most common non-skin malignancy in women.

Question 11

Describe the epidemiology of fibroadenomas.

Answer 11

Can occur at any age in reproductive period but often when 30 and younger.

Question 12

When are phyllodes tumours most common?

Answer 12

In the 6th decade of life.

Question 13

Describe the epidemiology of breast cancer.

Answer 13

Rare before 25 years old (apart from if family background).
Incidence rises with age.
Most occur when older than 55.
Average 64yo.

Question 14

How do we classify pathological conditions of the breast?

Answer 14

1. Disorders of development: milk line remnants, accessory axillary breast tissue.
2. Inflammatory conditions: acute mastitis, fat necrosis.
3. Benign epithelial lesions.
4. Stromal tumours.
5. Gynaceomastia.
6. Breast carcinoma.

Question 15

What is the commonest microorganism responsible for acute mastitis?

Answer 15

Staphylococcus aureus.

Question 16

How does the microorganisms get in to infect in acute mastitis?

Answer 16

From nipple cracks and fissures.

Question 17

How will a patient with acute mastitis present?

Answer 17

Erythematous painful breast with pyrexia.

May produce breast abscess.

Question 18

How do you treat acute mastitis?

Answer 18

Expressing milk and antibiotics.

Question 19

How does fat necrosis present?

Answer 19

Mass, skin changes or mammographic abnormality, often with history of trauma/surgery. Thus can mimic carcinoma clinically and mammographically.

Question 20

What benign epithelial lesions can be seen?

Answer 20

Fibrinocystic change: commonest breast lesion, may present as a mass/mammographic abnormality.
Mass can disappear after fine needle aspiration.

Question 21

Describe the histology of fibrocystic change.

Answer 21

Cyst formation, fibrosis and apocrine metaplasia.

Question 22

What stromal tumours can be identified histologically?

Answer 22

1. Fibroadenomas.
2. Phyllodes tumours.
3. Lipoma.
4. Leiomyoma.
5. Hamartoma.

Question 23

Describe the presentation of fibroadenomas.

Answer 23

Present with a mobile mass or mammographic abnormality.

Seen as a breast mouse as it is mobile and elusive. Can be multiple and bilateral.

Question 24

Describe fibroadenomas macroscopically.

Answer 24

Well circumscribed, rubbery, greyish/white.

Question 25

Describe the histology of a fibroadenomas.

Answer 25

Composed of a mixture of epithelial and stromal elements.

Localised hyperplasia rather than true neoplasm.

Question 26

What are phyllodes tumours?

Answer 26

Rare before 40.
Present as masses/mammographic abnormalities.
Benign, borderline and malignant types (most benign, only 5% malignant).
Can be very large and involve the entire breast.

Question 27

How do you manage phyllodes tumours?

Answer 27

Excised with wide margin.

Question 28

What is the histological appearance of phyllodes tumours?

Answer 28

Nodules of proliferating stroma covered by epithelium.

Stroma more cellular and atypical than that in fibroadenomas.

Question 29

What are the risk factors for breast cancer?

Answer 29

1. Female.
2. Uninterrupted menses.
3. Early menarche (<11yo).
4. Late menopause.
5. Reproductive history.
6. Breast feeding.
7. Obesity and high fat diet.
8. Exogenous Oestrogen.
9. Geographic influence.
10. Atypical changes on previous biopsy.
11. Previous breast cancer.
12. Radiation.
13. Genetics: BRCA1/2.

Question 30

What 2 ways do we classify breast carcinoma?

Answer 30

1. In situ and invasive.

2. Ductal and lobular.

Question 31

What is in situ carcinoma?

Answer 31

Neoplastic population of cells limited to ducts and lobules by basement membrane. Myoepithelial cells are preserved.
Does not invade into vessels and thus cannot metastasise and kill the patient.

Question 32

What is DCIS?

Answer 32

Ductal Carcinoma In Situ.
It is a precursor of invasive carcinoma.
Can spread through ducts and lobules and be very extensive.

Question 33

What does DCIS show histologically?

Answer 33

Central necrosis with calcification.

Question 34

What does DCIS show on a mammogram?

Answer 34

Mammographic calcifications (clusters/linear and branching)/mass.

Question 35

What is Paget’s disease?

Answer 35

Cells can extend to nipple skin without crossing basement membrane.
Unilateral red and crusting nipple.
Eczematous/inflammatory conditions of the nipple should be concerning.

Question 36

Compare invasive carcinoma from DCIS.

Answer 36

Neoplastic cells invade beyond bm into stroma in invasive.
In invasive it can invade into vessels and thus metastasise into lymph nodes and other sites.
Usually presents as a mass or mammographic abnormality.
By time cancer is palpable in invasive 50% will have axillary metastasis.
Peau d’orange suggests involvement of lymphatic drainage of skin.

Question 37

How is invasive breast carcinoma classified?

Answer 37

1. Invasive ductal carcinoma (70-80%). 35-50% 10 year survival.
   A: Well differentiated: tubules lined with atypical cells.
   B: Poorly differentiated type: sheets of pleomorphic cells.
2. Invasive lobular carcinoma (5-15%). Infiltrate cells in a single file, cells lack cohesion.
   Other types include tubular and mucinous.

Question 38

How does Breast Cancer spread?

Answer 38

1. Lymph nodes via lymphatic: usually in ipsilateral axilla.
2. Distant metastasis via bv: bone, lungs, liver and brain.
3. Invasive lobular carcinoma spread to peritoneum,retroperitoneum , leptomeninges, GIT, ovaries, uterus.

Question 39

What factors determine prognosis in breast cancer?

Answer 39

1. In situ vs invasive.
2. Tumour stage (TNM).
3. Tumour grade.
4. Histologic subtype: IDC NST has poorer diagnosis.
5. Molecular classification and gene expression profile.

Question 40

What is gene expression and why is it important in breast cancer?

Answer 40

Microfarads used to examine the expression patterns of lots of genes in tissues from breast cancer patients.
Computer cluster analysis of patterns led to identification of about 17 marker genes that can correctly identify about 90% of women who eventually develop metastasis.

Question 41

How do we investigate and diagnose breast cancer?

Answer 41

Triple approach:

1. Clinical: history, family history and examination.
2. Radiographic imaging: mammogram and USS.
3. Pathology: core biopsy and fine needle aspiration cytology (FNAC).

Question 42

What is mammographic screening?

Answer 42

A screening programme inviting women ages 47 to 73 to 2 view mammograms every 3 years in an aim to detect small impalpable cancers and pre-invasive cancer before it gets worst.
Looks for asymmetric densities, parenchyma deformities and calcifications. Any abnormalities are assessed using further imaging, core biopsy and FNAC.

Question 43

What are the therapeutic approaches in breast cancer?

Answer 43

Local and regional control:

1. Breast surgery: mastectomy, breast conserving surgery (patients choice etc).
2. Axillary surgery: extend depending on whether there are involved nodes.
3. Post-op radiotherapy to chest and axilla.

Question 44

What is sentinel lymph node biopsy?

Answer 44

Reduces the risk of postoperative morbidity.

Intraoperative lymphatic mapping with dye to see where breast lymph drainage is and thus where likely metastasis are.

Question 45

What are the therapeutic approaches to breast cancer?

Answer 45

1. Chemotherapy – if benefits thought to outweigh
   the risks; if given before surgery = neoadjuvant – 2. 2. Hormonal treatment, e.g. tamoxifen – depending
   on oestrogen receptor status (approximately 80% of
   cancers are ER positive)
2. Herceptin treatment – depending on 3. Her2 receptor
   status (approximately 20% of cancers are Her2
   positive). Herceptin = trastuzumab = humanised
   monoclonal antibodies against the Her2 protein

Question 46

What is Her2?

Answer 46

Member of human epidermal growth factor receptor family.

Encodes a transmembrane tyrosine kinase receptor.

Question 47

How do we improve survival from breast cancer?

Answer 47

1. Early detection.
2. Neoadjuvant chemotherapy.
3. Herceptin.
4. Gene expression profiles.
5. Prevention in familial cases: genetic screening, prophylactic mastectomy.