Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Molecular Basis of Disease > Breast cancer > Flashcards

Breast cancer Flashcards

1
Q

What is the most frequent cancer in women?

A

Breast cancer (1/3 female cancer in UK)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How common in breast cancer?

A

Quite common

  • 1.67M new cases world wide in 2012
  • 55,000 new cases annually in UK
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What percentage of breast cancers are hereditary and what gene mutations cause them?

A

7-10%

BRCA1/2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the rest of breast cancer (which aren’t hereditary)?

A

Sporadic (about 90% are)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What % of breast cancers are preventable?

A

27%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the >10 yr survival for breast cancer (female only) in UK?

A

78%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Why can breast cancer in men be worse than for women?

A

It is diagnosed late because they dont expect it and most cases are sporadic –> worse prognosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What decreases breast cancer risk in post menopausal women?

A

Physically active
fewer menstrual cycles (when they start and when menopause starts)
increased parity
breastfeeding >6 months

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What hormone is involved in breast cancer development?

A

oestrogen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the earliest evidence of oestrogen’s importance in breast cancer?

A

In Italian villages in 1700s it was shown that nuns had higher incidence of cancer than villagers (who had kids)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What has been happening to breast cancer incidence in the UK since 1980s?

A

It has been increasing

  • partially due to mammographic screening being introduced in 1988
  • also had a spike due to a hormone replacement therapy
  • we like to think it is leveling off now
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What oncogenic events lead to cancer development

A

DNA damage
Proto-oncogenes
Tumour suppressor gene damage –> decreased apoptosis
Angiogenic factors release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What can cause DNA damage?

A

UV light

irradiation (e.g. women who had TB X-rays after war)

chemicals (e.g. alcohol)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is a proto-oncogen?

A

A normal gene which, when altered by mutation, becomes an oncogene that can contribute to cancer.

Tend to drive cell cycle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Give an example of a tumour suppressor gene

A

p53

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Where do the growth factors for cancer and its supporting blood vessels come from?

A

Cancer cells and surrounding cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Give examples of proto-oncogens

A

C Myc

Ras

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What pattern of expression do oncogenes have?

A

Dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What cause most breast cancer deaths?

A

Metastases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the seed and soil theory of cancer?

A

Cancer cells will only metastasize to sites depending on the primary cancer (selectivity of sites)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the main breast cancer metastasis sites?

A

Through blood and lymph: brain, liver, bone (due to specific chemoattractant molecles)

Creeping across breast: lung

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the ‘golden standard’ test for diagnosing metastases?

A

Check if it has spread to lymph node

Sentinal lymph node status

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are stage 1 metastases?

A

local

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are stage 2 metastases?

A

loco-regional

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are stage 3 metastases?

A

regional/distant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What are stage 4 metastases?

A

regional and distant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Obviously early diagnosis is important to prevent metastasis. But why shouldn’t we do mammographic screenings?

A

Because we don’t want false postives (including people who have cancer which will never kill them)

Because since we do not know how serious it is we may over-treat the patient

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What has been happening to breast cancer mortality since 1975 and why?

A

It has significantly decrease by about -38% due to improved treatment and introduction of tamoxifen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Quickly go over the different cell types and what they do in the normal breast

A

Luminal epithelial cells: produce milk

Myoepithelial cells: contract to eject milk

Intralobular fibroblasts sit around these

All of this is regulated hormonally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Which cell type do most solid tumours (not just breast) come from?

A

Epithelial cells

Breast: luminal epithelial cells (95% of cancers)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Why are women more sussceptible to breast cancer

A

Oestrogen

It helps cell division- e.g. Monthly increase in cellularity to prep for pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What kind of tumours are those that arise from myoepithelial cells?

A

benign

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What kinds of tumours are those that arise from intralobular fibroblasts?

A

Fibrocystic diseases - common and benign

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What do you see in histological slide of cancer cells?

A

De-differentiation
increased mitoses
pleomorphic neuclei

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Are most diagnosed breast cancers in situ or invasive?

A

In situ

This is why we might be over treating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

How is breast cancer diangosed?

A

Found during screening
Symptomatic disease diagnosis
Checked with triple assessment
Further checking of receptor biology

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is pleomorphism?

A

variable size/ shape of nuclei, increased nuclear size, hyperchromasia (increased DNA content)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What is the triple assessment?

A

Clinical
Imaging: X ray/ MRI
Pathology (checking histology)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Do we see the same pathological changes in all cancers?

A

No

40
Q

What receptors are checked for in breast cancers and with what?

A

Oestrogen receptor: Immunohistochemistry

Progesterone receptor: Immunohistochemistry

HER2: Immunohistochemistry and FISH

41
Q

Are there any breast cancers that can’t be diagnosed with receptor biology?

A

Yes, triple negative breast cancer (there are other subtypes)

42
Q

What kind of hormone is oestrogen?

A

steroid

43
Q

How is oestrogen made?

A

By aromatase enzyme system from cholesterol

44
Q

Where is oestrogen made?

A

pre-menopause: ovaries

Post menopause: mainly adipose tissue (like to obesity and breast cancer)

45
Q

What does oestrogen do (role in cancer)?

A

regulates growth and differentiation in breasts, ovaries, skeleton and cardiovascular system

46
Q

What kinds of oestrogen are there and which ones are more relevant to breast cancer?

A

Oesterone (E1) binds to ERalpha - least abundant, post-menopausal

Oestrodiole (E2) binds to ERa and ERb - most potent and abundant in both men and women

Oestriol (E3) binds to ERb during pregnancy and in fetus; adult levels v. low

47
Q

What are the hypotheses for oestrogen induced carcinogenesis?

A

E binds to oestrogen receptor–> increased proliferation of mammary cells –> increased likelihood of mutations during DNA synthesis

E metabolites bind DNA : produce (depurinating) DNA adducts (this leads to genotoxicity and possible mutations)

48
Q

Are E metabolites carcinogenic?

A

Yes

49
Q

Describe the structure of the oestrogen receptor

A

Two types:
Intracellular nuclear hormone receptors
Homo- or hetero- dimerise (i.e.αα or ββ or αβ)

G protein coupled receptor GPR30 (less well understood)

50
Q

What kind of oestrogen receptor has most breast cancer research been done on?

A

nuclear hormone receptors

ERα
(ESR1 gene product, breast and ovary)

ERβ
(ESR2 gene product, diverse tissue distribution)

51
Q

What are the structural domains of the oestrogen receptor?

A

AF-1 and AF-2: transcription factors (activation domain)

DBD: DNA binding domain

LBD:ligand binding domain

52
Q

What do the AF1/2 domains do?

A

bind regulatory regions of DNA and control transcription. May act independently or in combination

53
Q

What does DBD do?

A

anchors the receptor on the DNA at sites known as ‘hormone response elements’ or oestrogen response elements

54
Q

What does the LBD do?

A

binding site for oestrogen

55
Q

Why do we have trouble studying the ER protein?

A

the protein is so big that we can only crystallize parts of the domain

56
Q

How does ER activation lead to cell proliferation?

A

E binds ER at LBD

ER moves to nucleus

Receptor dimerisation (homo and /or hetero)

Dimers bind DNA via DBD

Recruitment of co- regulatory proteins

Gene transcription

57
Q

How does the oestrogen receptor activate cell proliferation?

A

it may complex with EGFR and on-receptor tyrosine kinases (e.g. Src) - increased Ca2+ and nitric oxide production

MAPK/ERK pathway

PI3K/AKT pathway

may activate G protein coupled GPR30

58
Q

What are the treatments for breast cancer?

A 
Surgery
Radiotherapy
Chemo
Hormone therapy
Biological therapy
59
Q

What is the log and kill hypothesis?

A

states that a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells.

60
Q

How can the log and kill hypothesis be applied to treatment after surgery?

A

After significant debulking via surgery, chemo is used to kill a certain number of cells in each round, decreasing total tumour mass (despite regrowth between treatments).

The surgical debulking gives the constant log and kill process an added advantage (like a start line moved forward)

61
Q

So, why is surgery important for breast cancer?

A

Surgery is important for preventing metastases and improving the effect of chemotherapy

62
Q

TRUE or FALSE? A much lower dose of radiation is used for radiotherapy than for imaging

A

FALSE

A much higher dose is used

63
Q

What is the mechanism of radiotherapy?

A

Photons from high energy radiation enter the tissue and exit and cause damage to DNA - therefore causes cell death

64
Q

Radiotherapy is delivered in a fractionated manner

A

The total treatment is divided up into several, smaller doses

65
Q

Is radiotherapy effective if done alone?

A

No you must do it in combination with other things like cancer

66
Q

Does radiotherapy cause cancer?

A

No

67
Q

How does ionising radiation work?

A

Electrons are released from the atoms of the molecules in the tissue causing formation of ions

68
Q

When and how was chemotherapy discovered?

A

A reduction in WBCs (especially B cells) noted in soldiors exposed to mustard gas - nitrogen mustard

2 doctors used nitrogen mustard to treat lymphomas

69
Q

How does nitrogen mustard work?

A

alkylating agent

70
Q

How do most chemotherapies work?

A

Damaging or preventing DNA synthesis

71
Q

What kind of cells does chemo work best on?

A

Rapidly dividing ones

72
Q

How do alkylating agents work?

A

They form cross links between DNA strands and stop them from unwinding

Especially making covalent cross link on N7 of guanine in DNA –> cytotoxicity

73
Q

How does cyclophsphamide work?

A

More complicated than nitrogen mustard

activated by P450 –> alkylating agent

74
Q

What are antimetabolites?

A

Analogs of naturally occuring metabolites of RNA and DNA synthesis which lead to nucleotide depletion/incorporation in DNA and thus lead to cell death

75
Q

What are plant alkaloids

A

Enter the cell–> bind to tubulin and inhibit beta and alpha tubulin assembly –> cannot make mitotic spindle in M phase

76
Q

Name types of chemo

A 
Alkylating agents (cyclophosphamide, nitrogen mustard)
Antimetabolites
Plant alkaloids
antitumour antibiotics
Topiramase inhibitors
77
Q

What are antitumour antibiotics?

A

natural products made by streptomyces bacteria which block cell growth by interfering with DNA and genetic material in cell

78
Q

Where was vinca alkaloid found?

A

Pacific Yew tree

79
Q

Give examples of antitumour antibiotics

A

Doxorubicin and derivative epirubicin, bleomycin, mitomycin C, actinomycin, topiramase inhibitors, etoposidem mitoxantrone

80
Q

What do topiramase 1 and 2 inhibitors do?

A

Topiramase 1 and 2 inhibitors (slop unwinding during replication and transcription –> causes breaks in DNA–> apoptosis)

81
Q

What are chemo side effects?

A 
Nausea
Vomitting
Dyspepsia
Loss of appetite
Tinnitus
Blurred vision
Fever
Hypersensitive skin rash
WBCs can't divide - infections
Gut cells don't divide - GI problems
Loss of hair
Effects on fingernails
82
Q

What treatment did Beatson give patients with advanced breast cancer (pre-menopausal)?

A

Remove ovaries (start menopause)

83
Q

What proportion of breast cancer patients were found to respond to endocrine manipulations?

A

one-third

84
Q

What are some methods of hormonal manipulation

A

Ovarian ablation
Selective ER modulators(SERMS)
Aromatase inhibitors

85
Q

What was the first precision med in cancer?

A

SERMS

86
Q

Name a SERM and how it works?

A

Tamoxifen
metabolised by P450 in liver (similar to E2) and made into active form –> competes with E2 at ER –> binding leeds to G0/1 arrest

87
Q

What is the active form of tamoxifen?

A

4-hydroxytamoxifen

88
Q

TRUE or FALSE Tamoxifen looks like E2 and thus binds to the same place in the ER

A

FALSE it looks completely different and binds to a different bit

89
Q

How effective are SERMs?

A

Very
Tamoxifen 5yr post-op: 50% less recurrences, 25% increased survival
10yrs post-op 16% difference in breast cancer recurrence

90
Q

Why are SERMs so effective?

A

70% of breast cancers are ER +ve

91
Q

What are the side effects of tamoxifen and why do they occur?

A

Good: Protects post-menopausal women from osteoporosis - acts as ER agonist in bone

Bad:

  • significantly increases uterine cancer risk - partial agonist in endometrium
  • Increased CVD risk due to increased triglyceride component in serum
  • cancer cell resistance
92
Q

Does tamoxifen work in most meopausal women?

A

Sometimes

93
Q

Who are aromatase inhibitors for?

A

Post-menopausal women

94
Q

Give examples of aromatase inibitors

A

anastrazole, letrozole and exemestane

95
Q

How do aromatase inhibitors work?

A

Bind to aromatase and prevent synthesis of oestrogens from parent compounds (e.g. androgens)

96
Q

How are aromatase inhibitors different from SERMs?

A

They work upstream to prevent synthesis of endogenous oestrogens

Molecular Basis of Disease (28 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions