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CAN > L22: Hormone Driven Cancers > Flashcards

L22: Hormone Driven Cancers Flashcards

1
Q

What are the risk factors for breast cancer

A 
Age 
High fat diet 
High BMI 
Shorter duration of breastfeeding 
Previous breast disease
Family history 
Oestrogen exposure 
Early menarche 
Late menopause 
No children 
Alcohol smoking 
Radiation
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2
Q

How can you have exposure to oestrogen

A

Oral contraceptive pill

Hormonal replacement therapy

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3
Q

What happens to the risk of breast cancer when you stop taking OCPs/HRT

A

Decreases

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4
Q

What is the treatment for local disease

A

Lumpectomy
Mastectomy
Adjuvant radiotherapy
Adjuvant systemic therapy

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5
Q

What is the treatment for invasive breast cancer

A

Wide local excision with lymph nodes
Radiotherapy
Neo adjuvant chemotherapy
Adjuvant systemic therapy

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6
Q

What is the purpose of systemic therapy

A

Prevent metastasis to other organs

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7
Q

What does the systemic therapy depend on

A

The nature of cancer:

I.e if hormone dependent or not

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8
Q

If the cancer is oestrogen dependent what therapy can we use

A

Taxomifen
Aromatase inhibitors
Gonodotrophin releasing hormone analogue

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9
Q

Who is aramotase inhibitors used on

A

Post menopausal woman

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10
Q

Who is gonodotrophin releasing hormone used on

A

Pre menopausal woman

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11
Q

If the cancer is not hormone dependent i.e oestrogen dependent what therapy would we use

A

Chemotherapy

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12
Q

When we take the tumour out via surgery what is done to the lump

A

Histology

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13
Q

What is luminal a breast cancer

A

Oestrogen receptor positive
Progesterone positive
HER2 negative

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14
Q

Where is oestrogen receptor present

A

In the nucleus

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15
Q

What bins to oestrogen receptors

A

Oestrogen

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16
Q

What is oestrogen receptor in the nucleus stabilised by

A

HSP90

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17
Q

What happens to oestrogen receptor (ER) when oestrogen binds to it

A

Dimerises and phosphorylated

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18
Q

What happens to HSP90 protein when oestrogen binds to ER

A

Loses its effect

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19
Q

When we have dimerised ER what bind to it

A

Co activator molecules in

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20
Q

What does the co-activator bound form of ER have exposed

A

Transcriptional actor factor - TAF 1+2

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21
Q

What is the role of TAF 1 & 2

A

Binds to DNA and causes the transcription of genes of progesterone receptor, IGF, TGF-alpha

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22
Q

What happens to IGF and TGF-alpha that is released

A

Binds to insulin growth receptors (IGF) and TGF-alpha receptors on the surface of the cell in a autocrine fashion

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23
Q

What type of receptor is TGF-alpha receptor

A

Tyrosine kinase receptor

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24
Q

When the receptors are activated what pathway becomes activated

A

MAP pathway

PI-3 kinase pathway

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25
Q

What does the MAP and PI-3 Kinase pathway result in

A

Proliferation

Cell growth

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26
Q

Name an example of a selective oestrogen receptor modulator (SERM)

A

Tamoxifen

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27
Q

How does tamoxifen work

A

1) It binds to oestrogen receptors
2) ER cannot be dimerised and become phosphorylated
3) this stop co-activator molecules from binding
4) TAF 2 regions are blocked so transcription of IGF and TGF-alpha are decreased
5) TAF1 is still active

28
Q

How can tamoxifen be used

A

Neo-adjuvant- to reduce the size of the tumour
Adjuvant systemic therapy- to reduce risk of metastasis
In combination with chemotherapy

29
Q

What are the side effects of tamoxifen

A

Menopausal symptoms of hot flushes, sweats
Deep vein thrombosis
Increased risk of endometrial cancer

30
Q

What can develop when we use tamoxifen long term

A

Resistance

31
Q

What are the 2 types of tamoxifen resistance that can occur

A

De novo: despite ER present there are mutation in the epigenetic region
Acquired resistance

32
Q

What are the resistance mechanism for tamoxifen

A
  • change in balance of corepressor and co-activators (more present) which increases gene transcription
  • mutated ER
  • tamoxifen removed from the cells
33
Q

What are the other pathways involved apart from oestrogen that can activate ER

A

1) EGF can activate the MAP and PI-3 kinase pathway by binding to EGFR
2) In the MAP pathway, ERK1/2 moves to the nucleus to directly phosphorylate ER on serine 118
3) therefore ER is activated without the binding of oestrogen i.e tamoxifen has no effect
4) in the PI-3 kinase pathway, AKT, can phosphorylate ER

34
Q

Name a drug that is an aromatase inhibitor

A

Letrozole

35
Q

What is the normal role of aramatase enzyme

A

Covert testosterone into oestrogen (2-cell hypothesis)

36
Q

What is the role of aromatase enzymes

A

Inhibit the production of oestrogen

37
Q

Why is aromatase enzyme used in post menopausal woman

A

Because oestrogen is not released in the ovaries, it is made in the local tissue by testosterone conversion

38
Q

What are the side effects of aromatase inhibitors

A 
Hot flushes
Vagina dryness
Nausea
Rashes
Osteoporosis
39
Q

What can happen if you use letrozole long term

A

Resistance

40
Q

If you develop resistance with both tamoxifen and letrozole what is the 3rd line of therapy

A

Fulvesterant

41
Q

What is fulvesterant

A

A pure anti-oestrogen

42
Q

Name a gonodotrophin releasing hormone analogue used in pre-menopausal woman

A

Goserelin

43
Q

Describe how goserelin works

A

1) goserelin is an analogue of Luteinising hormone releasing hormone receptor (LHRHR) in the pituitary gland
2) this stimulates the LH/FSH release in the short term
3) a continuing exposure causes the down regulation of receptors so FSH production is decreased via a feedback loop
4) less stimulation to the ovaries via FSH
5) less oestrogen is produced

44
Q

What is luminal b breast cancer criteria

A

ER positive

Either HER2 Positive or high Ki-67+ progesterone negative

45
Q

What mutations are present in luminal b

A 
Cyclin d 
EGFR
PI-3 kinase
PTEN
Tp53
46
Q

Are luminal b breast cancer responsive to endocrine therapy

A

Yes more aggressive form so chemotherapy may be required

47
Q

How do we decide if we should add chemotherapy

A

Oncotype DX: a pool of genes identified to be associated with progressive disease e.g luminal B cancer.
There are 15 genes associated with breast cancer you can look for the 15 genes and generate a score and give chemotherapy to high scorers.

48
Q

What are the other types of breast cancer

A

HER2 over expressing

Basal like

49
Q

What is HER2 breast cancer

A

When HER2 is overexpresed

50
Q

What is the treatment for HER2 over expressing breast cancer

A

Herceptin

51
Q

What is basal like breast cancer

A

ER negative
PR negative
HER2 negative
Associated with BRAC1

52
Q

What is the treatment for basal like breast cancer

A

Chemotherapy

PARP inhibitors

53
Q

What is the role of BRCA1 and BRCA2

A

DNA repair

54
Q

What type of penetrance does BRCA1/2 have

A

High penetrance

55
Q

What are the other genes that can be associated with basal like breast cancer

A 
Tp53
ATM
Chek2
Palb2
RAD51
56
Q

What are the risk factors for endometrial cancer

A 
Bleeding after menopause 
Early menarche 
Late menopause 
Irregular menstruaton 
HRT
57
Q

What is endometrial cancer stimulated by

A

Unopposed oestrogen i.e if you have oestrogen but not progesterone

58
Q

Why is tamoxifen a risk factor for endometrial cancer

A

1) tamoxifen blocks TAF2 but TAF1 is active

2) the uterus is sensitive to TAF1 receptor stimulation

59
Q

What is the treatment for endometrial cancer

A

Hysterectomy

60
Q

What are the risk factors for prostate cancer

A

Age
Family history- BRCA2
High fat and diet

61
Q

What are the early signs and symptoms of prostate cancer

A

Difficulty to pass urine
Nocturia
Pain in urination
Blood in urine

62
Q

What are the advanced symptoms of prostate cancer

A 
Impotence 
Tiredness
Loss of appetite 
Pain in hips and spine- due to bone metastasis 
Spinal nerve compression
63
Q

How is prostate cancer diagnosed

A

PSA test
Digital rectal examination
Transrectal biopsy

64
Q

What are the treatment options for prostate cancer

A

Active survelliance- regular psa and biopsy to see if cancer is advancing
Radical prostectomy- surgery
Radiotherapy: external bias or brachytherapy (planting radiation near prostate)
Hormone treatment- for metastatic disease

65
Q

What are the hormone treatments for prostate cancer

A

Goserelin
Anti-androgen e.g abireterone
Orchidectomy

CAN (25 decks)

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