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BS3003 > 9th March - Early Detection > Flashcards

9th March - Early Detection Flashcards

1
Q

What are the survival rates for breast cancer and cervical cancer in comparison with if it is detected late?

A

Cervical - 93% – 15%

Breast - 93% – 6%

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2
Q

What are the three main methods of early detection?

A

Being aware of the symptoms
Self examination
Screening

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3
Q

What are the two main types of screening?

A

Universal, Mass Population - i.e. everyone within a certain age range

Selective - targeting specific groups of people e.g. those with BRCA1 mutations

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4
Q

Outline the main method of breast screening

A

Mammography - 2 X-rays are taken of each breast
Looking for lumps and calcification
Reduces the number of deaths from breast cancer by about 1300 a year

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5
Q

What are the two main forms of bowel screening?

A

DIY kits - take feacal sample

Sigmoidoscopy

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6
Q

Why screen?

A

For early detection of disease
For early detection of disease recurrence
For early detection of acquired resistance to treatment

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7
Q

What is a biomarker?

A

A biological marker found in blood, other body fluids, or tissues that is a sign of normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for disease or condition

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8
Q

What are the three main uses of biomarkers?

A

Diagnostic
Prognostic
Predictive

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9
Q

What are the traits of an ideal biomarker?

A 
Specific
Sensitive
Predictive
Clincal importance
Minimally invasive
Reflect kinetics
Robust
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10
Q

What are the genetic biomarkers for brain cancer?

A

Abnormal methylation of p16, CDKN2B, p14ARF

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11
Q

What are the genetic biomarkers for cervical cancer?

A

Hypermethylation of MYOD1, CDH1, and CDH13

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12
Q

What are the genetic biomarkers for oral cancer?

A

Hypermethylation of p16, p14 and RB1

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13
Q

What are the genetic biomarkers for colorectal, oesphageal, liver and pancreatic cancer?

A

EGFR, KRAS, TP53 and ERBB2 mutations

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14
Q

What are the genetic biomarkers for breast and ovarian cancer?

A

BRCA1 and BRCA2

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15
Q

What is prostate specific antigen?

A

A biomarker of cancer, produced by epithelial cells of the prostate and detected in the ejaculate

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16
Q

How is cancer diagnosed?

A

Using a tissue biopsy using immunohistochemistry and pathological evaluation

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17
Q

What is the diagnostic biomarker for prostate cancer?

A

Alpha-foetoprotein

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18
Q

What is the diagnostic biomarker for ovarian cancer?

A

Cancer antigen 125

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19
Q

What is the diagnostic biomarker for colorectal cancer?

A

Carbohydrate antigen 19-9

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20
Q

What are prognostic biomarkers?

A

Biomarkers which indicate the likely course of the disease in an untreated individual

21
Q

what are predictive biomarkers?

A

Biomarkers which identify subpopulations of patients who are not likely to respond to a given therapy

22
Q

What is a biomarker for highly aggressive multiple myeloma?

23
Q

Why do we need predictive biomarkers?

A

Therapy cost-effectiveness
Improved clinical benefit and safer drugs due to more targeted therapy
Reduces unnecessary treatment and adverse effects
Highlighting acquired resistance to therapy

24
Q

What is a biomarker for aggressive breast cancer?

A

ERBB2 amplification

25
Q

What is a predictive biomarker for metastatic melanoma?

A

BRAF mutation - indicates responsiveness to Vemurafenib

26
Q

What are the main advantages of circulating biomarkers over solid biopsy?

A

In a solid biopsy you only sample a section of the tumour therefore there is no indication of mutations in other regions and therefore have no idea of resistance. In a liquid biopsy it represents tumour heterogeneity and is much less invasive

27
Q

What are the different methods of liquid biopsies?

A

Cell free DNA
Exosomes
Circulating tumour cells

28
Q

When was cell free DNA discovered?

29
Q

What is cell free DNA?

A

Circulating DNA derived by apoptosis/necrosis/active secretion

30
Q

Why is cell free DNA a useful biomarker?

A

There are elevated levels in cancer due to tumour cell turnover and shows mutations

31
Q

What are the advantages of using cell free DNA as a biomarker?

A

Very easy to obtain and measure
Can be extracted from anyone
Extremely useful predictive, prognostic, and diagnostic marker
Represents tumour heterogeneity
Easy to track the acquisition of new mutations/CNA
Information on any stage of cancer

32
Q

What are the disadvantages of using cell free DNA as a biomarker?

A

Results are hugely affected by haemolysis
Low yields
No RNA/protein data
Not always the best option e.g. sometimes CSF is more useful in brain cancer

33
Q

Is cfDNA useful as an early diagnostic marker?

A

Currently in clinical trials for breast cancer - for those with suspicious mammograms

34
Q

Is cfDNA useful as a prognostic biomarker?

A

ESR1 mutations in metastatic breast cancer who had prior exposure to aromatic inhibitors to AI therapy, have reduced progression free survival. This can be detected by both mutations and copy number alterations in cfDNA.

35
Q

Is cfDNA useful as a predictive biomarker?

A

Yes, certain genes which are amplified in cfDNA indicates likelihood of relapse

36
Q

What are circulating tumour cells?

A

CTC’s are the ‘seeds’ of metastasising tumours

37
Q

Why are CTCs a useful treatment monitoring tool?

A

Changes in CTC levels will reflect tumour progression

38
Q

What are the advantages of CTCs?

A 
Can be stained 
FISH
qRT-PCR
Expression analysis
Cell culture
39
Q

What are the disadvantages of CTCs?

A

No consensus on how a CTC is defined
Rare (1:100000)
Difficult to isolate

40
Q

What are the different types of CTCs?

A

Traditional - viable nucleus, CK positive, CD45 negative and large with an irregular shape

CK negative - thought to be cancer ‘stem cells’

Apoptotic - traditional CTCs undergoing cell death

Small - CK positive, CD45 negative, similar in size to white blood cells

CTC clusters - groups of CTCs clustered together, may contain all of the above

41
Q

Are CTCs useful as early diagnostic markers?

42
Q

What are exosomes?

A

Circulatory mirNA packaged in microvesicles

43
Q

What are the advantages of exosomes as biomarkers?

A

Easy to obtain - can get straight from blood
Stable in circulation
Dynamically change in cancer
100s of different miRNAs to look for

44
Q

Are exosomes a useful biomarker for treatment response?

A

Yes as they dynamically change in cancer

45
Q

What are the disadvantages of exosomes as biomarkers?

A 
Individual variability
Haemolysis
Anti-coagulant
Requires normalisation
Amount will depend on choice of processing
46
Q

Give an example of a diagnostic prostate cancer miRNA

A

let-7c is decreases in prostate cancer

47
Q

What is the TNM staging system?

A

A formal system of tumour grading which is based exclusively on the anatomical extent of the disease i.e. tumour size/depth, presence of metastasis, lymph node spread

48
Q

When was the TNM staging system developed?

BS3003 (26 decks)

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