Physiology of the breast

Question 1

There are 3 main parts of the breast:

- Glandular tissue

Answer 1

a. 15-20 lobules, responsible for producing milk
b. Within the lobules there are alveoli – modified sweat glands – that secrete milk.
c. Glandular tissues have receptors for oestrogen & progesterone (released by the ovaries) and prolactin (released by the pituitary gland)

Question 2

Glandular tissue

Answer 2

i. Oestrogen and progesterone cause alveolar cells to divide and increase in number, enlarging the lobule
ii. Without hormones, glandular cells undergo apoptosis – after menstruation, alveolar cells die and breast tissue is replaced by fat.

Question 3

Other parts of the breast:

Answer 3

2. Stroma, containing adipose (fat tissue), is the majority of the breast.
3. Lymphatic vessels are found just below the skin covering the breast. They drain lymph – cellular waste & WBCs.

Question 4

Breast Cancer (BRCA)

Answer 4

Breast cancer is uncontrolled growth of epithelial cells in the breast, forming a tumour.

Question 5

Subtypes

Answer 5

1. Ductal carcinoma in-situ (DCIS) – tumours grow from the wall of the ducts into the lumen. If left untreated, they cross basement membrane. DCIS does invade surrounding tissues.
2. Lobular carcinoma in-situ (LCIS) – clusters of tumour cells grown within lobules, causing alveoli to enlarge – ducts are not invaded. LCIS does not invade surrounding tissues.

Question 6

Some breast cancers have hormone receptors, allowing them to grow in the presence of hormones:

Answer 6

ER or PR-receptor involvement indicates that the tumour is hormone-dependant tumour, so is more likely to respond to hormonal treatments. The prognosis is more favourable.
HER2 is a transmembrane tyrosine kinase which regulates growth, survival & migration. If a cancer is HER2+, it will be more aggressive, so prognosis is poorer.

Question 7

ER and HE2

Answer 7

ER = oestrogen receptor, PR = progesterone receptor, HER2 = human epidermal growth factor receptor type 2 (aka ErbB2)

Question 8

Carcinoma in situ:

Answer 8

Carcinoma in situ is proliferation of cancer cells within the epithelial tissue without invasion of the surrounding tissue. In contrast, invasive carcinoma invades the surrounding tissue. Perineural and/or lymphovascular space invasion = associated with more aggressive disease.

Question 9

Luminal A

Answer 9

• DCIS
• ER +
  PR +
  HER2 -
• 15% with p53 mutation
• Chemo
  Radiation
  Hormone

Question 10

Luminal B

Answer 10

• DCIS
• ER +
  PR +
  HER2 +
• 30% with p53 mutation
• Chemo
  Radiation
  Hormone

Question 11

Triple negative (basal like)

Answer 11

• DCIS
• ER -
  PR -
  HER2 -
• Most with p53 mutation
  BRCA 1 involvement
  High levels of Ki-67 protein
• Chemo
  Radiation
  Biological (Non-HER2 targeted)

Question 12

HER2 type

Answer 12

• DCIS
• 70% - HER2 +
  30% - HER2 -
• 75% with p53 mutation
• Biological (HER-2 targeted)

Question 13

Risk factors-11

Answer 13

• 60-years-old (as median age of diagnosis is 60-65)
• Oestrogen exposure (e.g. late menopause, use of oral contraceptives and early menstruation
• Genetics
o BRCA 1 & 2 genes play a rule in DNA repair; mutations in these genes confer 80-90% lifetime risk
o TP53 – tumour protein 53
o ERBB2 (HER-2) – receptor tyrosine-protein kinase
• Ethnicity may be classed as a risk factor – more common in white populations
• Obesity, smoking and alcohol use
• Nulliparity – not having children
• Stress (initiates DNA damage)
• Socio-economic status – actually less common if living in deprived areas
Avoiding the above (where possible), breastfeeding and engaging in physical activity are protective – reducing the risk of developing BC.

Question 14

Screening

Answer 14

Mammography is an X-Ray, offered to all women aged 50-70 every 3 years. 1/100 screened women in the UK have cancer detected through breast screening. Around 8 in 10 of these are invasive cancers. See radiography for further details.
1% of women have breast cancer (and therefore 99% do not).
80% of mammograms detect breast cancer when it is there; 20% of mammograms miss signs of cancer
10% of mammograms detect breast cancer when it’s not there (and therefore 90% correctly return a negative result).

Probability of a 40-50-year old with breast cancer = 7.47%

Question 15

Presentation

Answer 15

C may present in a variety of ways, including:
Hard, painless lump or swelling
Swelling under armpit (indicates spread to lymph nodes)
Breast immobile
Dimpling, thickening & change in colour (orange) of skin (indicates blockage of lymphatic vessels and involvement of skin)
Retraction/ inversion of the nipple (caused by fibrosis of lactiferous ducts)
Discharge from nipple (paget disease)

Question 16

Diagnosis

Answer 16

Breast cancer does not cause pain, until it spreads to surrounding tissues.
Median age of diagnosis is 60-65.
• Feeling of a breast lump
• Mammography is also used to confirm diagnosis. About 20% of all cancers of the breast detected by mammographic screening are ductal carcinoma in situ (DCIS).
• Breast biopsy, using methods such as needle aspiration/ ultrasound guided/ stereotactic or open
o Needle biopsy – fluid and tissue from lump is drawn
o Open biopsy (lumpectomy) – all/ part of a lump is removed & tested for malignancy
• Breast MRI helps better identify the breast lump or evaluate an abnormal change on a mammogram
• Breast ultrasound shows whether the lump is solid or fluid-filled
• FBC, LFT, bone profile may help ensure diagnosis, and evaluate invasive nature of cancer
• CT, CAP and bone scan if high risk, to show whether the breast cancer has spread elsewhere

Question 17

When Diagnosed…

Answer 17

When diagnosed at its earliest stage, around all women with breast cancer will survive their disease for five years or more, compared with 3 in 20 women when the disease is diagnosed at the latest stage.

The following groups are more likely to be unhappy with their care: Long term/multiple conditions other than cancer; ethnic minorities; young patients (16 – 35 years); those attending London Hospitals; LGBT community. 

Question 18

Classification -TNM staging - • Tumour size (& extent, of the main tumour)

Answer 18

o T1= <2cm
o T2= 2-5cm
o T3= >5cm
o T4= direct extension to chest wall or skin

Question 19

Lymph Nodes (the number of nearby lymph nodes that have cancer)

Answer 19

o N1 = mobile ipsilateral lymph nodes
o N2 = fixed to one another or other structures
o N3 = infraclavicular or ipsilateral internal mammary and axillary nodes

Question 20

Metastasis (the development of secondary malignant growths at a distance from a primary site of cancer)

Answer 20

oM0 = no metastasis 
oM1= contralateral lymph nodes or any distant metastases
oMx= Distant metastasis cannot be assessed.

Question 21

G3 – grading pathology

Answer 21

• Grade I (well differentiated/low grade)
o cancer cells look similar to normal cells and grow very slowly
o In low grade invasive ductal carcinoma, glands are still seen
• Grade II (moderately differentiated)
o cancer cells look more abnormal and are slightly faster growing
• Grade III (poorly differentiated/high grade)
o cancer cells look very different from normal cells and tend to grow quickly
o In high grade invasive ductal carcinoma, a sheet of cells is seen, where nuclei are pleomorphic (varies in shape and size); no glands can be seen