Breast Pathology

Question 1

Describe the normal structure of the breast

Answer 1

The breast is made up of glands in a background of connective tissue and adipose tissue. There are 15-20 main ducts which open into the nipple. Each main duct branches off into many terminal ducts. Each terminal duct ends at a lobule. Each lobule is composed of numerous acini. Each acini is lined by an inner secretory layer made of columnar or cuboidal epithelium and an outer layer of myoepithelial cells which contain actin and can contract

Question 2

Where do most breast lesions arise from?

Answer 2

the epithelium of the terminal duct lobular unit

Question 3

What are the different clinical presentations of breast pathology?

Answer 3

lump, general lumpiness, discomfort or pain, nipple changes, nipple discharge, change in shape of breast, breast asymmetry, skin changes/tethering, mammographic screening detected

Question 4

How does mammography work?

Answer 4

mammography looks at the radiographic density in the breast tissue - fibrous tissue is more dense than adipose and breast pathology looks more dense than normal breast tissue - also looks at patterns of calcification

Question 5

How is breast cancer diagnosed?

Answer 5

a biopsy - either an FNA (cytology) or a tru cut biopsy (piece of tissue)

Question 6

What is fibrocystic change?

Answer 6

a common benign breast disease that involves bilateral multifocal dilation of ducts with or without cyst formation, fibrosis, adenosis (proliferation of acinous structures) and apocrine metaplasia (where epithelial cells become pink and granular)

Question 7

What is a fibroadenoma?

Answer 7

a solitary well circumscribed benign mass - a stromal tumour with an epithelial component - usually presents as a lump

Question 8

What are the risk factors for breast cancer?

Answer 8

age, genetic factors (sporadic and familial), high oestrogen, environmental and dietary influences, past history of certain breast diseases, radiation and ethnicity

Question 9

Which genes are commonly mutated in sporadic cases of breast cancer?

Answer 9

p53 and HER2

Question 10

What is HER2?

Answer 10

A gene for an epidermal growth factor receptor. If there is too much expression of HER2 then it will result in abnormal cell proliferation. This occurs in about 20% of breast cancer cases.

Question 11

What percentage of breast cancer cases have a specific mutation in BRCA1, BRCA2 or p53?

Answer 11

5%

Question 12

Why does a mutation in BRCA1, BRCA2 or p53 lead to breast cancer?

Answer 12

these genes are tumour supressor genes which are involved in cell cycle arrest - if there is a mutation in the other allele then it will lead to a lack of DNA repair so mutations will be passed on to daughter cells

Question 13

What else is BRCA1 associated with?

Answer 13

ovarian cancer

Question 14

How else can breast cancer be inherited?

Answer 14

through the interaction of multiple low risk susceptibility genes and environmental factors

Question 15

What are some causes of increased oestrogen which may predispose to breast cancer?

Answer 15

early menarche, late menopause, no pregnancies, use of HRT, postmenopausal obesity

Question 16

Why is breast feeding protective against breast cancer?

Answer 16

because breast feeding supresses ovulation so reduces oestrogen

Question 17

Why is oestrogen a risk factor for breast cancer?

Answer 17

because oestrogen stimulates proliferation in breast which increases the risk for DNA mutations

Question 18

What is breast hyperplasia and is it a risk for breast cancer?

Answer 18

non neoplastic proliferation of breast epithelium - only a risk if there is atypia

Question 19

What is in situ carcinoma of the breast?

Answer 19

Malignant population of cells confined to ducts and/or acini, no invasion through basement membrane - leads to increased risk of developing invasive tumour

Question 20

What are the two types of in situ carcinoma of the breast?

Answer 20

ductal carcinoma in situ and lobular carcinoma in situ

Question 21

What is Paget’s disease of the nipple?

Answer 21

when ductal carcinoma in situ goes up to the nipple where it causes erythema, inflammation and exudate of the nipple

Question 22

What is peau d’orange?

Answer 22

where the skin of the breast looks dimpled like an orange - it is due to invasion of the lymphatics and is a possible presentation for an invasive carcinoma

Question 23

What are the two main types of invasive carcinoma?

Answer 23

invasive ductal and invasive lobular

Question 24

Which is the most common type of invasive carcinoma?

Answer 24

invasive ductal

Question 25

In which part of the breast is the breast cancer most commonly found?

Answer 25

the upper outer quadrant

Question 26

Where does breast cancer commonly metastasise to?

Answer 26

lymphatics (axillary, supraclavicular, internal mammary nodes), and via the blood spreads to the lungs, bone, liver and brain

Question 27

How are breast cancers graded?

Answer 27

scores for acinar/tubule formation, nuclear pleomorphism and mitotic index - grade as low, intermediate or high

Question 28

Why are breast cancers immunohistochemically stained for oestrogen receptors?

Answer 28

because if there are oestrogen receptors on the tumour then tamoxifen can be used in treatment

Question 29

Why is HER2 amplification assessed in breast cancers?

Answer 29

because if there is HER2 amplification then herceptin (transtuzumab) - a monoclonal antibody that blocks the HER2 receptor can be used in treatment

Question 30

How is breast cancer staged?

Answer 30

TNM - tumour size, lymph nodes and metastases