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CAN > Hormones and cancer > Flashcards

Hormones and cancer Flashcards

1
Q

Non- modifiable risk of breast cancer

A
  • Strongest = age (peak = 50-70)
  • Previous breast disease (e.g. benign)
  • Family history (BRCA and others)
  • Hormone-related factors
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2
Q

Modifiable risks of Bc

A

High socio-economic group
(obesity, alcohol, high feat diet, smoking)
-less pregnancies
-less likley to breastfeed

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3
Q

What are the hormone related risks of breat cancer

A

Oestrogen and breast cancer

  • early menarche before 12
  • late menopause
  • or no child or first child over 30

breast feeding reduces the risk of breast cancer

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4
Q

How do we test for the oestrogen receptor

A

-get a sample of tumor from biopsoy
-if postive 1% of cells need to express receptor

determines risk of reoccurance of if sutible for hormone therapy

oestrogen receptor positive cancer are more susceptible to hormone therapy

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5
Q

What does treatment depend on

A

how aggressive cancer is

does it have mets

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6
Q

Where can BC métastase

A
  • in organs like
    • skeleton bone
    • liver
    • lung
    • brain
    • skin
    • ovaries
    • GI system
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7
Q

How would you treat BC

A

Hormone therapy
- SERM such as Tamoxifen
- Aromatase Inhibitor (post menopausal)
- Gonadotrophin-releasing hormone analogue (pre- menopausal)

+ chemotherapy

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8
Q

When would you do chemotherapy to reduce metastic spread

A

-if tumor is poorly differenated (grade 3 or above)
-if theres lymph node involvement
-if oestrogen receptor negative

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9
Q

What is luminal A breast cancer

A
  • HER2 negative
  • ER (oestrogen receptor) and pgR positive
  • reoccurrence is low
  • few mutated genes
  • responds to endocrine therapy and less to chemotherapy
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10
Q

How does the oestrogen receptor E2 effect cells

what binds, what happens after binding etc

A

Set the scene
-oestrogen is located on the nucleus surface and is associated with HSP90

  1. E2 (oestrodiol) passes through cell membrane
  2. binds onto oestrogen receptor
  3. causes dimmersation + phosphyrlation and lose association with HSP90
  4. the receptor is now on, the change in shape exposes TAF 1 band 2 reigons
  5. these reigons bind onto DNA
  6. causing the transcription of genes like insulin growth factor, progestrone receptor, TGF alpha
  7. these will then leave the cell, and bind back onto the cell to cause proliferation -> stimulating tumor growth

Asssuming: Co-actiavator is TAF 1+2, repressor is HSP90

IGF for example would bind onto MAP kinase pawthays, or PI3 kinase to increase expression of cyclins

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11
Q

Hormone therapy

SERM

what does it mean, example, risk reduction

A

stands for Selective oestrogen receptor modulators e.g. Tamoxifen
-reduces reoccurance by 42% with 5 years of tretment
-reduces risk of developing contralateral primary tumor
-improves survival by 22% in early cancers

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12
Q

Tamoxifen

dosage,use

A

-its SERM
-tablet 20mg daily
uses
– can be used
- neo-adjuvant -. to decrease size of tumor before surgery
- adjuvant systemic therapy: reduces metastsic spread
- can be used with chemo or alone

need to check if they have the oestrogen receptor

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13
Q

How do SERMs like tamoxifen work

A
  • competitive inhibitor for oestrogen at the receptor
  • it blocks the TAF-2 region on OR
    • prevents recurritemnt of co-activatiors
    • so no gene transcription so stops cell proliferation (cytotastic)
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14
Q

What is the problem with tamoxifen

A
  • TAF 1 is still active
    • long term problem
    • can cause risk of endomterial cancer
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15
Q

What are the side effects of tamoxifen

A
  • essitently putting person through menopause
  • Menopausal symptoms such as hot flushes and sweats (40% of women)
  • Fatigue (25%)
  • Painful joints (25%)
  • Nausea (20%)- usually only at first

Less common

  • vaginal discharge/ discomfort, water retention, weight gain, headaches, depression, hair thinning

Rare

  • Increased risk of deep vein thrombosis, pulmonary embolism
  • Increased risk of endometrial cancer
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16
Q

Tamoxifen resistance

How does resistant to tamoxifen occur

there are two ways

A

**EGFR upregulation
**- the cells begin to upreguates EGFR on surface
- these increase the EGFR signalling pathways (MAPK)
- ERK 1/2 directly phosphyrlates OR at serine residues
- allowing for transcription of genes
- we dont need oestrogen in this pathway, so who would tamoxifen compete with
- so we become resistant

**Tamoxifen can amplify cyclin D
**-cyclin D expression is amlified
-cyclin D acts as co-activator for receptor
-this happens because of cyclin D not oetsrogen so tamoxifen has nothing to compete with

some success in blocking cdk inhibitors in conjunction with tamoxifen has improved survival

17
Q

Where does most oestrogen production come from post menopausal women

A

adipose tissue

mechanism
-oestrogen levels controlled by conversion of testosterone to oestradiol in the adipose tissues by aromatase enzymes
-Androgens are converted in adipose tissue by aromatase enzyme into E2. This enters cell binds to ER

18
Q

How do aromatase inhibtiors work

A

they prevent the enzyme aromatase from coverting testosterone into oestrogen in adiopcytes
therefore decreasing oestrogen levels
can’t activate OR like that anymore

19
Q

Why is it preferential to give post menopausal women armostase inhibitors compared to tamoxifen

A

ATAC trial found

  • found armostase is just as effective as tamoxiifen
  • with less side effects
  • so aromatase more prefernetial for post menopausla women
20
Q

What are the side effects of aromatase inhibitors

A

Hot flushes and Vaginal dryness

  • Nausea
  • Rashes
  • Joint stiffness
  • Raised cholesterol
  • Osteoporosis
  • Neurological effects on extremities
    • pins and needles in hands and feet
21
Q

What is the NHS guidance with SERMs

A
  • we use tamoxifen first, for a couple years so not too long, when there’s resistance …
  • use aromatase inhibitors
  • then aromatase inhibitors will develop resistance → Eventually chemo
22
Q

What drug is used if premenopausal

A

Goserelin
is a LHRH agonisnt

23
Q

How does groselin work

A
  • binds to LHRH recpetors in pituitary
  • initially stimulates FSH/LH then after continuous exposure, causes downregulation of receptors and lower FSH production
  • without FSH/LH production im guessing ovaries can’t make oestrogen
24
Q

How often is groselin administered

A

1 a month injection

25
Q

What is the luminal type B Bc

A
  • OR positive
  • HER 2 postove or high Ki-67 (cells proliferate more), or have PR positive
  • often aneuploid
  • mutations in D1, EGFR1 and PTEN, TP53
  • can respond to endocrine therapy but more sensitive to chemo
26
Q

What is onoctype DX

A

-21 genes tested to wotk out whether person would benefit more from chemo or hormone therapy
-generates a reoccurqance score
– higher reoccurrence means more likely to return
- they have lots of mutations
- would want to give chemo
- if they have a lower score
- can give endocrine therapy

27
Q

What is the second common cause of death in men after lung cancer

A

prostate cancer

6th most common cancer, diagnosed at older age, third most diagnosed

28
Q

What are the causes of prostate cancer

A
  • age
    • as you increase age risk increases
  • strong genetic link
    • things like BRCA2, GSTP1
  • hugh fat and meat diet
29
Q

What is early prosate disease defined as

A
  • Tumour still confined to prostate
  • Symptoms limited as tumour so small
30
Q

What are the signs and symptoms of early stage prostate cancer

A

Signs & symptoms mainly urinary

  • Difficulty passing urine
  • Nocturia
  • Pain on urination
  • Haematuria
31
Q

What are the signs and symptoms of advanced prostate disease

A

Signs & symptoms include:

  • Impotence
  • Tiredness
  • General feelings of unwellness
  • Loss of appetite
32
Q

What symptoms can bone metatise+ spinal nerve compression cause in prostate cancer

A

Bone metastases can cause:

  • Pain in the hips and spine
  • increased fractures

Spinal nerve compression

  • Paraesthesia or weakness
  • Incontinence
33
Q

How do we diagnose prostate cancer

A
  • PSA
    • Gamma Seminoprotein or Kallikrein-3
    • goes up when you have benign prostatic hyperplasia
      • a lot of men will have a positive test
    • not traced in some men who don’t have cancer (20% of men)
  • digital rectal examination
  • these days we use MRI
34
Q

How do we treat prostate cancer

A

Treatment options for non-metastatic prostate cancer include:

  • Deferred treatment/ active surveillance: (low grade tumours + PSA <10ng/ml): PSA every 3 months & repeat
    • biopsy after 2y
  • Radical prostatectomy: (tumour localised to gland)
  • Radiotherapy (disease in pelvis or higher PSA)
  • External beam (Intensity modulated - IMRT)
  • Brachytherapy
35
Q

When do we use hormone treatment for prostate cancer

A
  • patients are too frail or cannot do radiotherapy
  • they have metatsisis
  • or use neoadjuvant → to reduce tumour size
36
Q

What hormone treatment can we use to treat prostate cancer

A

goserelin

36
Q

How does goserelin work in prostate cancer treatment

A
  • binds to LHRH in the hypothalamus
  • cause tumour flare, → have breast pain
  • long term reduce testosterone
  • so reduce the amount of metastasis
  • reduce the size of the prostate gland
37
Q

We can also use anti-androgen based therapy for prostate cancer

How does that work?

A
  • compete with androgen receptor with binding with testosterone
  • examples include Abiraterone

  • best way is to go for both treatments
    • do maximum androgen blockades used both therapies

CAN (10 decks)

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