9th March - Early Detection

Question 1

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

Answer 1

Cervical - 93% – 15%

Breast - 93% – 6%

Question 2

What are the three main methods of early detection?

Answer 2

Being aware of the symptoms
Self examination
Screening

Question 3

What are the two main types of screening?

Answer 3

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

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

Question 4

Outline the main method of breast screening

Answer 4

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

Question 5

What are the two main forms of bowel screening?

Answer 5

DIY kits - take feacal sample

Sigmoidoscopy

Question 6

Why screen?

Answer 6

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

Question 7

What is a biomarker?

Answer 7

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

Question 8

What are the three main uses of biomarkers?

Answer 8

Diagnostic
Prognostic
Predictive

Question 9

What are the traits of an ideal biomarker?

Answer 9

Specific
Sensitive
Predictive
Clincal importance
Minimally invasive
Reflect kinetics
Robust

Question 10

What are the genetic biomarkers for brain cancer?

Answer 10

Abnormal methylation of p16, CDKN2B, p14ARF

Question 11

What are the genetic biomarkers for cervical cancer?

Answer 11

Hypermethylation of MYOD1, CDH1, and CDH13

Question 12

What are the genetic biomarkers for oral cancer?

Answer 12

Hypermethylation of p16, p14 and RB1

Question 13

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

Answer 13

EGFR, KRAS, TP53 and ERBB2 mutations

Question 14

What are the genetic biomarkers for breast and ovarian cancer?

Answer 14

BRCA1 and BRCA2

Question 15

What is prostate specific antigen?

Answer 15

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

Question 16

How is cancer diagnosed?

Answer 16

Using a tissue biopsy using immunohistochemistry and pathological evaluation

Question 17

What is the diagnostic biomarker for prostate cancer?

Answer 17

Alpha-foetoprotein

Question 18

What is the diagnostic biomarker for ovarian cancer?

Answer 18

Cancer antigen 125

Question 19

What is the diagnostic biomarker for colorectal cancer?

Answer 19

Carbohydrate antigen 19-9

Question 20

What are prognostic biomarkers?

Answer 20

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

Question 21

what are predictive biomarkers?

Answer 21

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

Question 22

What is a biomarker for highly aggressive multiple myeloma?

Answer 22

TIMP1

Question 23

Why do we need predictive biomarkers?

Answer 23

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

Question 24

What is a biomarker for aggressive breast cancer?

Answer 24

ERBB2 amplification

Question 25

What is a predictive biomarker for metastatic melanoma?

Answer 25

BRAF mutation - indicates responsiveness to Vemurafenib

Question 26

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

Answer 26

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

Question 27

What are the different methods of liquid biopsies?

Answer 27

Cell free DNA Exosomes Circulating tumour cells

Question 28

When was cell free DNA discovered?

Answer 28

1948

Question 29

What is cell free DNA?

Answer 29

Circulating DNA derived by apoptosis/necrosis/active secretion

Question 30

Why is cell free DNA a useful biomarker?

Answer 30

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

Question 31

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

Answer 31

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

Question 32

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

Answer 32

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

Question 33

Is cfDNA useful as an early diagnostic marker?

Answer 33

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

Question 34

Is cfDNA useful as a prognostic biomarker?

Answer 34

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.

Question 35

Is cfDNA useful as a predictive biomarker?

Answer 35

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

Question 36

What are circulating tumour cells?

Answer 36

CTC's are the 'seeds' of metastasising tumours

Question 37

Why are CTCs a useful treatment monitoring tool?

Answer 37

Changes in CTC levels will reflect tumour progression

Question 38

What are the advantages of CTCs?

Answer 38

``` Can be stained FISH qRT-PCR Expression analysis Cell culture ```

Question 39

What are the disadvantages of CTCs?

Answer 39

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

Question 40

What are the different types of CTCs?

Answer 40

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

Question 41

Are CTCs useful as early diagnostic markers?

Answer 41

No

Question 42

What are exosomes?

Answer 42

Circulatory mirNA packaged in microvesicles

Question 43

What are the advantages of exosomes as biomarkers?

Answer 43

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

Question 44

Are exosomes a useful biomarker for treatment response?

Answer 44

Yes as they dynamically change in cancer

Question 45

What are the disadvantages of exosomes as biomarkers?

Answer 45

``` Individual variability Haemolysis Anti-coagulant Requires normalisation Amount will depend on choice of processing ```

Question 46

Give an example of a diagnostic prostate cancer miRNA

Answer 46

let-7c is decreases in prostate cancer

Question 47

What is the TNM staging system?

Answer 47

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

Question 48

When was the TNM staging system developed?

Answer 48

1958