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YR2: MCD Cancer > Cancer as a Disease – Breast Cancer > Flashcards

Cancer as a Disease – Breast Cancer Flashcards

1
Q

What is special about the breast as an organ?

A

It’s the only organ that develops after birth

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2
Q

Where do the vast majority of breast cancers originate?

A

Luminal epithelium of the breast (> 90%)

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3
Q

Describe the two layers of epithelial cells in the mammary gland.

A

Luminal epithelium

Myoepithelium

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4
Q

What is found between the tubules in the mammary gland?

A

Fatty stromal cells

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5
Q

What is special about the myoepithelial cells?

A

They have a contractile property, thus can squeeze the luminal epithelial cells when full of milk globules in lactation

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6
Q

Where are oestrogen receptors expressed in the breast?

A

ONLY expressed by luminal cells

Not all luminal cells express oestrogen receptors (only ~ 10)

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7
Q

Describe the response to oestrogen in a normal breast.

A

Response to oestrogen is to stimulate growth
Cells that express oestrogen receptors do NOT grow in response to oestrogen
Act as a beacon + produce growth factors that stimulate the growth of nearby cells

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8
Q

How is the response to oestrogen different in breast cancer?

A

Cells displaying oestrogen receptors directly respond to oestrogen as a growth factor + stimulate their own growth

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9
Q

What is the difference between lobular and medullary carcinoma?

A

Lobular: tumour has some resemblance of the architecture of the gland (tubules of some form)
Medullary: tumour cells don’t look anything like the epithelial cells from the mammary gland

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10
Q

What specific type of breast cancer accounts for almost 85% of breast cancers?

A

Infiltrating ductal carcinoma

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11
Q

What percentage of breast cancers is ER positive?

A

80%

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12
Q

State 7 risk factors for breast cancer.

A 
Early age of onset of menstruation  
Late age to menopause  
Age to 1st full-time pregnancy  
Some contraceptive pills  
Some HRT
Obesity
Diet
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13
Q

Where is the oestrogen receptor normally located?

A

Cytosolic receptor

Bound to a heatshock protein

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14
Q

What happens when oestrogen binds to ER?

A

Oestrogen binds to ER + then 2 ERs dimerise + translocate to the nucleus (with oestrogen bound)
Dimer binds to oestrogen response elements in the DNA sequence + regulates transcription

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15
Q

What are the 4 most important target genes for the ER transcription factor?

A

Progesterone receptor
Cyclin D1
c-myc
TGF-alpha

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16
Q

Why does high dose therapy with synthetic oestrogens cause breast tumour regression in post-menopausal women with breast cancer?

A

High-dose therapy overstimulates the hormonal system leading to downregulation of ER so the cells are no longer responsive to oestrogen

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17
Q

How does the presence of ER affect prognosis?

A

GOOD prognosis in women

Worse prognosis in male breast cancer

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18
Q

What are three methods of reducing oestrogen action in the breast?

A

Ovarian suppression
Blocking oestrogen production by enzymatic inhibition
Inhibiting oestrogen responses

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19
Q

At what point during the menstrual cycle is oestrogen at its highest?

A

End of the follicular phase

20
Q

How do post-menopausal women make oestrogen? Where does this occur?

A 
Aromatisation of androgens
Fatty tissue (+ liver + muscles)
21
Q

What are 2 methods of ovarian ablation?

A

Surgical oophorectomy

Ovarian irradiation

22
Q

What are the problems associated with Surgical oophorectomy and Ovarian irradiation?

A

They are irreversible

23
Q

Describe a reversible and reliable medical ovarian ablation technique.

A

LHRH agonists bind to LHRH receptors in the pituitary leading to receptor downregulation + suppression of LH release + inhibition of ovarian function, including oestrogen production

24
Q

Name an important ER receptor blocker.

A

Tamoxifen

25
Q

What is a SERM?

Why is tamoxifen considered a SERM?

A

Selective oestrogen receptor modulator
Anti-oestrogenic in the breast
Oestrogenic in bone + cardiovascular system

26
Q

Name a drug that is a pure anti-oestrogen, showing no oestrogen like activity at all. What are the negatives of this drug?

A

Faslodex

Blocks oestrogen everywhere in the body, thus increases risk of osteoporosis + CVD

27
Q

What is raloxifene?

A

A SERM: it is oestrogenic in bone + anti-oestrogenic in the breast + uterus

28
Q

What are the problems associated with tamoxifen?

A

Increased incidence of endometrial cancer (oestrogenic in the uterus)
Increased risk of stroke, DVT, cataracts

29
Q

Which adrenal hormones are aromatised in post-menopausal women?

A

Androstenedione (+ testosterone, to a lesser extent)

30
Q

What does the aromatase complex produce from androstenedione?

A

Oestrone Sulphate

31
Q

What does the aromatase complex consist of?

A

cytochrome P450 heme containing protein

NADPH cytochrome P450 reductase

32
Q

What are the two types of aromatase inhibitor?

A

Irreversible

Reversible

33
Q

How do Irreversible aromatase inhibitors work?

A

Bind to active site of aromatase complex
Causes formation of alkylating species + covalent bonds
Irreversibly inactivates the enzyme

34
Q

Give an example of an aromatase inhibitor

A

Exemestane

35
Q

Give an example of a reversible aromatase inhibitor.

A

Anastrozole

36
Q

What can progestin therapy be used for?

A

Metastatic breast cancer

37
Q

What is the main progestin used for metastatic breast cancer?

A

Megestrol acetate

38
Q

What is a big problem with endocrine therapy?

A

Resistance develops

Relapse occurs

39
Q

Women in which age range are targeted for breast cancer screening? How often are they asked to go for screening?

A

50-64 yrs

Every 3 years

40
Q

What proportion of breast tumours are first spotted by the women themselves?

A

> 90%

41
Q

What may have contributed to the rising incidence but falling mortality of breast cancer?

A

Early diagnosis (public health message to self examine)
Chemo/ Radiotherapies can now be more focussed + effective
Availability of hormonal therapies

42
Q

What is the major treatment approach to breast cancer?

A

Surgery

Followed by chemo/ radiotherapy

43
Q

What is given as adjuvant therapy for breast cancer?

A

Endocrine therapy

Kills any tumour cells that broke away from the tumour mass/ weren’t removed in surgery

44
Q

What are the 3 pathways of endocrine therapy?

A

Ovarian suppression (pre-menopausal)
Blocking oestrogen production by enzymatic inhibition
Inhibiting ER

45
Q

How is oestrogen primarily made? (pre-menopausal)

A

Hypothalamus stimulates the pituitary through LHRH
Causes release of LH + FSH
Stimulates ovary to make large quantities of oestrogen

46
Q

What is the most common side effect of Tamoxifen therapy?

A

Hot flushes

47
Q

How do reversible aromatase inhibitors work?

A

Bind reversibly to active site, competing with androstenedione

YR2: MCD Cancer (18 decks)

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