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MCD > Cancer 12: breast cancer > Flashcards

Cancer 12: breast cancer Flashcards

1
Q

How many cancer deaths is breast cancer accountable for?

A

1 in 5

It is the leading female cancer

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2
Q

Where does a majority of breast cancer originate?

A

luminal epithelium (>90%)

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3
Q

What is the structure of the mammary gland?

A
  • between tubules you have fatty stromal cells
  • epithelial cells line the lumen of the tubules
  • there are TWO types of epithelial cell

luminal epithelial cells
myoepithelial cells

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4
Q

What do myoepithelial cells do?

A
  • they have a contractile phenotype and will contract in response to the correct signals
  • they are responsible for the formation of tubules
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5
Q

what cell are oestrogen receptors ONLY present on?

A

-luminal epithelial cells

they respond to oestrogen to stimulate growth in adjacent cells

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6
Q

What happens to the effect of oestrogen receptors in cancer?

A

the cells directly respond to oestrogen as a growth factor and therefore stimulates their growth

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7
Q

What occurs with a benign tumour?

A

there is proliferation of luminal cells but there is still myoepithelium surrounding it

it then develops into either LOBULAR CARCINOMA or MEDULLARY CARCINOMA or just a CARCINOMA

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8
Q

What type of carcinoma accounts for almost 80% breast cancers?

A

infiltrating ductal carcinoma

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9
Q

What type of staining is useful in diagnosing the breast cancer?

A

immunohistochemical staining using antibodies against the ER

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10
Q

What percentage of breast cancers are estrogen-receptor positive?

A

about 80%

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11
Q

How does the estrogen receptor lead to breast cancer?

A

oestrogen binds to the ER inside the cell, two ER come together to form a dimer which is then able to enter the nucleus

  • once in the nucleus gene expression is induced by binding to specific DNA sequences called estrogen response elements
  • this increases cell proliferation resulting in breast cancer
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12
Q

What are the most important estrogen regulated genes?

A
  • progesterone receptor
  • cyclin D1
  • c-myc
  • TGF-alpha
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13
Q

What therapy’s do pre and post menopausal women respond to?

A

1/3 premenopaousal women respond to oophorectomy

postmenopausal women respond to high-dose therapy with synthetic estrogens

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14
Q

What are the major treatment approaches on breast cancer?

A
  • surgery
  • radiation therapy
  • chemotherapy
  • endocrine therapy
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15
Q

How is endocrine therapy achieved?

A
  • ovarian suppression
  • blocking estrogen production by enzymatic inhibition
  • inhibiting estrogen responses
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16
Q

Where does oestrogen come from in pre and post menopausal women?

A
  • in premenopausal women the ovaries are the main site of oestrogne production
  • in postmenopausal women aromatisation of androgens in peripheral tissue is the main source
17
Q

How can ovarian ablation be carried out?

A
  • surgical oophorectomy

- ovarian irradiation

18
Q

How can reversible ovarian ablation occur?

A
  • luteinising hormone releasing hormone (LHRH) agonist
  • this binds to the LHRH receptor leading to a down regulation of the receptors

this suppresses LH release and inhibits ovarian function

19
Q

Give FOUR examples of LHRH agonists

A
  • goserelin
  • buserelin
  • leuprolide
  • triptorelin
20
Q

How can aromatase be inhibited?

A

aromatase inhibitors

prevent the conversion of androgens to oestrogen

21
Q

Give an example of an anti-estrogen

A

taxoxifen is a competitive inhibitor

  • they negate the stimulatory effects of estrogen by blocking the ER causing it tp be held in the G1 phase
22
Q

When is tamoxifen chosen as endocrine treatment?

A
  • metastatic disease in postmenopausal patients

- few side effects are reported with hot flushes being the most common

23
Q

What class of drug is tamoxifen?

A

SERM - selective estrogen receptor modulator

it is oestrogenic in bone so can help with post menopausal osteoporosis

it is also oestrogenic on the cardiovascular system so can decrease atherosclerosis risk in women

24
Q

What is tormifene?

A

-structural derivative of tamoxifen with similar antiestrogenic and estrogenic properties

25
Q

What is faslodex?

A

-pure anti-oestrogen

decreases tumur cell invasion

26
Q

What is raloxifene?

A

antitumour agent in animal

used in the treatment of osteoporosis in post menopausal women

27
Q

What are the problems associated with tamoxifen?

A
  • endometrial cancer
  • stroke
  • DVT
  • cataracts

to overcome these problems, prevention trials are being conducted with

  • faslodex
  • aromatase inhibitors
28
Q

What does aromatase do?

A
  • catalyses three separate steroid hydroxylations involved in the conversion of androstenedione to estrone
  • contains a cytochrome P450 heme
29
Q

What types of aromatase inhibitors are there?

A
  • suicide inhibitors

- reversible inhibitors

30
Q

What are suicide inhibitors?

A

-it initially competes with the natural substrate for the binding site, once bound the enzyme acts on the inhibitor causing it to form covalent bonds

31
Q

Give an example of a suicide inhibitor?

A

exemetase

32
Q

What are competitive inhibitors and give an example?

A

-bind reversibly to the active site

anastrozole

33
Q

What does progestin in the breast influence?

A

proliferation and differentiated function

34
Q

what are progestins used for?

A
  • endocrine treatment of uterine and breast cancer

- metastatic breast cancer as a second or third line treatment following selective estrogen

35
Q

What happens with endocrine treatment over time?

A

all patients become resistant to endocrine therapies and they relapse

therefore endocrine therapies must be used require additional therapeutic agents

36
Q

What are the risk factors of breast cancer?

A
  • early age of onset of merarche
  • late age to menopause
  • age at first full term pregnancy
  • some forms of the contraceptive pill
  • hormone replacement therapy
  • obesity
  • diet
37
Q

What does breast cancer therapy involve?

A

-mammography
between 50-64
-attend a screen once every three years
-90% of breast tumours are first spotted by women themselves

MCD (13 decks)

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