Repro 11.2.2 Breast Cancer

Question 1

How common is breast cancer?

Answer 1

Accounts for 20% of all malignancies in women
1 in 12 women develop breast cancer in their life
1% occurs in men
95% are adenocarcinomas (other malignant tumours of the breast are very rare

Question 2

What increases mens risk of breast cancer?

Answer 2

Klinefelter’s syndrome
Male to female transexuals
Men treated with oestrogen for prostate cancer

Question 3

Where are breast cancers most common?

Answer 3

Upper outer quadrant (50%)

Question 4

What are the risk factors for development of breast cancer?

Answer 4

Gender
Uninterrupted menses
Early menarche (<11)
Late menopause
Obesity and high fat diet
Exogenous oestrogens (HRT, OCP) 
Liver cirrhosis
(All to do with hormones)
Atypical changes on previous biopsy (4-5 times)
Previous breast cancer (x10)
Radiation

Question 5

What factors reduce risk of breast cancer?

Answer 5

Reproductive history - parity and age at first full term pregnancy and amount of pregnancies
Breast-feeding

Question 6

How does geography influence the risk of development of breast cancer?

Answer 6

Higher incidence in US and Europe. Possible explanation in diet, physical activity, breast-feeding and environmental factor

Question 7

What % of breast cancers are hereditary?

Answer 7

10%

Question 8

What genes are most commonly implicated in breast cancer?

Answer 8

3% of all breast cancers and 25% of hereditary breast cancers are attributed to mutations in BRCA1 or BRCA2
p53

Question 9

Which BRCA gene is also implicated in ovarian cancer?

Answer 9

BRCA2

Question 10

What are BRCA genes?

Answer 10

Tumour supressor genes - their proteins repair damaged DNA

Question 11

What % of the population have BRCA germ line mutations?

Answer 11

0.1%

Question 12

What is the lifetime breast cancer risk for female carriers of BRCA1?

Answer 12

60-85%

May undergo prophylactic mastectomy

Question 13

When are familial breast cancers usually diagnosed in comparison to sporadic cases?

Answer 13

20 years earlier on average

Question 14

What are the classification of breast carcinoma?

Answer 14

In situ or invasive

Ductal or lobular

Question 15

What are carcinomas in situ?

Answer 15

Neoplastic population of cells limited to ducts and lobules by basement membrane, myoepithelial cells are preserved
Does not invade into vessels and therefore cannot metastasise

Question 16

How do most DCIS present?

Answer 16

Mammographic calcifications (clusters or linear and branching) but can also present as a mass

Question 17

How does DCIS appear microscopically?

Answer 17

Often shows central necrosis with calcification

Question 18

How might DCIS spread?

Answer 18

Can spread through ducts and lobules and be very extensive

Question 19

What is DCIS?

Answer 19

Ductal carcinoma in situ. Non-obligate precursor of invasive carcinoma

Question 20

How can Paget’s disease present in the breast?

Answer 20

Unilateral red crusting nipple

Question 21

What might Paget’s disease of the nipple be mistaken for?

Answer 21

Eczematous or inflammatory conditions of the nipple - should be regarded as suspicious and biopsy performed

Question 22

What is the pathophysiology of Paget’s disease in the nipples?

Answer 22

Malignant cells can infiltrate epidermis via the mammary duct epithelium. The cells proliferate leading to thickening of the affected skin

Question 23

Define an invasive carcinoma.

Answer 23

Invaded beyond BM into stroma. Can invade into vessels and can therefore metastasise to lymph nodes and other sites

Question 24

How does an invasive carcinoma present?

Answer 24

Usually as a mass or mammographic abnormality. By the time a cancer is palpable more than half the patients will have axillary lymph node metastases

Question 25

What is peau d'orange?

Answer 25

Involvement of lymphatic drainage of the skin gives rise to a dimpled affect by the hair follicles as oedema swells the skin surrounding them. A clinical appearance of breast cancer

Question 26

What are the most common types of invasive carcinoma of the breast?

Answer 26

Invasive ductal carcinoma, no special type (IDC NST) (70-80%) Invasive lobular carcinoma (5-15%) Tubular, mucinous etc

Question 27

What is the appearance of well/poorly differentiated IDC NST?

Answer 27

Well-differentiated - tubules lined by atypical cells | Poorly-differentiated - sheets of pleomorphic cells

Question 28

What is the 10 year survival rate for IDC NST?

Answer 28

35-50%

Question 29

What is the microscopic appearance of invasive lobular carcinoma?

Answer 29

Infiltrating cells in a single file | Cells lack cohesion

Question 30

What is the prognosis of invasive lobular carcinoma?

Answer 30

35-50% 10 year survival rate

Question 31

What are the patterns of metastasis of breast cancer?

Answer 31

Lymph nodes via lymphatics (usually ipsilateral axilla) | Distant metastases via blood vessels - bone, lung, liver, brain

Question 32

Where might invasive lobular carcinoma spread?

Answer 32

``` Peritoneum Retroperitoneum Leptomeninges Gastrointenstinal tract Ovaries Uterus ```

Question 33

What factors determine the prognosis of breast cancer?

Answer 33

``` In situ v invasive Histological subtype - IDC NST has poorer prognosis Tumour grade Tumour stage Gene expression profile ```

Question 34

What is the basis of tumour staging?

Answer 34

Tumour size Locally advanced disease - invading into skin or skeletal muscle Lymph node metastases Distant metastases

Question 35

How is breast cancer investigated and diagnosed?

Answer 35

Triple approach: 1. Clinical - history, fx, examination 2. Radiographic imaging - mammogram and ultrasound scan 3. Pathology - fine needle aspiration cytology (FNAC) and core biopsy

Question 36

What is looked for in mammographic screening?

Answer 36

Asymmetric desities Parenchymal deformities Calcifications

Question 37

How are abnormalities seen in mammographic screening further assessed?

Answer 37

Further imaging FNAC Core biopsy

Question 38

What are the local treatment options for breast cancer?

Answer 38

Breast surgery - mastectomy or breast conserving surgery Axillary surgery - extent depending on whether there are involved lymph nodes (sentinel node sampling or axillary dissection) Post-operative radiotherapy to chest and axilla

Question 39

How is the type of breast surgery required determined?

Answer 39

Patient choice Size Site of tumour Size of breast

Question 40

What is sentinel lymph node biopsy?

Answer 40

Intraoperative lymphatic mapping with dye and/or radioactivity of the draining or 'sentinel' lymph node(s) - this is the one most likely to contain breast cancer metastases If the sentinel node(s) is negative axillary dissection can be avoided

Question 41

What is the systemic therapeutic approach to treatment of breast cancer?

Answer 41

Chemo (only if benefits thought to outweigh risks) | Hormonal/herceptin treatment (depending on hormone/Her2 receptor status)

Question 42

What is neoadjuvant chemotherapy?

Answer 42

Given before surgery

Question 43

What is Her2?

Answer 43

A member of the human epidermal growth factor receptor family Encodes a transmembrane tryosine kinase receptor

Question 44

What is herceptin?

Answer 44

humanised monoclonal antibodies against the Her 2 protein

Question 45

How do oestrogen receptors appear under the microscope?

Answer 45

Brown stained nuclei

Question 46

How do Her2 receptors appear under the microscope?

Answer 46

Blue stained nuclei, brown cytoplasm

Question 47

How is the survival for breast cancer improved?

Answer 47

``` Early detection Neoadjuvant chemo Use of newer therapies Gene expression profile Prevention of familial cases ```