Breast Cancer 2

Question 1

Why do breast cancers occur often?

Answer 1

High amount of growth factor and hormone stimulation received by the breast

Question 2

What are the stages that can change the breast?

Answer 2

Foetal, puberty, pregnancy, lactation, post lactation

Question 3

Ductal carcinoma in situ (DCIS) characteristics?

Answer 3

milk ducts are filled with carcinoma cells

Question 4

Lobular carcinoma in situ (LCIS) characteristics?

Answer 4

overfilling of the terminal duct lobular units in the atypical epithelial cells

Question 5

Different systems of subtyping breast cancers?

Answer 5

Histologic, clinical, intrinsic

Question 6

Histological subtyping of breast cancers?

Answer 6

morphology, includes in situ & invasive
looking at tissue histology it is possible to categorise the cancer according to where it is occurring

Question 7

Clinical subtyping of breast cancers?

Answer 7

expression of oestrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor (HER2).
Linked to treatment options
Some overlap

Question 8

Intrinsic subtyping of breast cancers?

Answer 8

genome-wide transcriptome analysis allows classification into 4 subtypes. Linked to prognosis & mechanistic characteristics
Links to prognosis and mechanisms of how the cancers are caused

Question 9

Most commonly mutated gene in BC?

Answer 9

TP53

Question 10

Gene mutation interaction in BC?

Answer 10

Multiple mutations can act cumulatively

Question 11

Role of p53 protein?

Answer 11

Detects DNA damage and regulates the cell cycle

Question 12

Which BC involved gene is not to do with DNA repair/proliferation?

Answer 12

GATA3

Question 13

Role of GATA3?

Answer 13

Normal development of breast tissue

Question 14

What are the two gene expression signatures that the intrinsic classification categorises BC into?

Answer 14

High grade-like pathway and pow grade-like pathway

Question 15

Two subtypes of low grade-like pathway?

Answer 15

Luminal A-like and luminal B

Question 16

Two subtypes of high grade-like pathway?

Answer 16

HER2-enriched, basal like

Question 17

WHich genes do the luminal A and B subtypes have?

Answer 17

Genes involved with eostrogen receptor

Question 18

WHich subtypes have the worse prognosis?

Answer 18

Those in the high grade-like pathway

Question 19

What % of BC cases have overexpression of oestrogen receptor?

Answer 19

70%

Question 20

What are ER+ BCs?

Answer 20

Ones that have an overexpression of the oestrogen receptor

Question 21

Result of oestrogen receptor activation?

Answer 21

Proliferation

Question 22

What are nuclear receptors?

Answer 22

Ligand activated gene regulators

Question 23

Inactive nuclear receptor?

Answer 23

Inhibitory proteins bound, preventing them from binding to DNA and controlling transcription

Question 24

Immediate result of nuclear receptor ligand binding?

Answer 24

Removal of the inhibitory complex and allows binding of coactivator proteins

Question 25

What are the coactivator proteins that can bring to the ER after oestrogen has bound?

Answer 25

FoxA1 and GATA3

Question 26

What are the defining signature genes consistently observed in ER+ breast cancers?

Answer 26

ER, FOXA1, GATA3

Question 27

Two hypotheses of how oestrogen causes cancer?

Answer 27

During menstrual cycle, oestrogen binding stimulates proliferation of mammary cells and may cause DNA damage accumulation Oestrogen metabolism produces genotoxic waste

Question 28

What is genotoxic waste?

Answer 28

waste that can cause DNA daamge

Question 29

What % of BC cases are PR+ve?

Answer 29

65%