cancer the facts

Cancer is not just one diseaseMore than 200 different types of cancer have been identified

What is cancer?

CANCER

Defining cancer

Cancer is an accumulation of abnormal cells that multiply through uncontrolled cell division and spread to other parts of the body by invasion and/or distant

metastasis via the blood and lymphatic system

MetastasisTumour growthNormal cells Abnormal cells

Invasion into surrounding tissues

Uncontrolled cell division

Spread via blood or lymphatic system

Incidence of cancer across the globe (2008, estimate)1

Estimated number of new cancer cases (% of total)

Africa (6%)Asia (48%)Europe (25%)Latin America and Caribbean (7%)Northern (13%)Oceania (1%)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International Agency

for Research on Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 06/06/2013.

Changing prevalence of cancer

Global cancer incidence and mortality rates continue to rise1

21.3 M

12.7 M

13.1 M

7.6 M

CASES DEATHS

2030

2008

20302002

25 M people living

with cancer*2

75 M predicted to be living with

cancer2

*Diagnosed in last 5 years

GROWING AND AGEING POPULATION

ADOPTION OF UNHEALTHY LIFESTYLES

IMPROVEMENT IN DIAGNOSIS/SCREENING

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International

Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 14/01/2013. 2. The International Agency for Research on Cancer. World Cancer Report 2008. Available from:

http://www.iarc.fr/en/publications/pdfs-online/wcr/, accessed on 06/06/2013.

Common cancers in men and women worldwide1

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International

Agency for Research on Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 06/06/2013.

16.5

13.6

109.77.9

4.94.4

3

3

27

Men (%) Lung (16.5)

Prostate (13.6)

Colorectum (10.0)

Stomach (9.7)

Liver (7.9)

Oesophagus (4.9)

Bladder (4.4)

Non-Hodgkin lymphoma (3.0)

Leukaemia (3.0)

Other and unspecified (27.0)

8.5

22.9

9.45.83.78.84.8

3.72.7

29.7

Women (%) Lung (8.5)

Breast (22.9)

Colorectum (9.4)

Stomach (5.8)

Liver (3.7)

Cervix uteri (8.8)

Corpus uteri (4.8)

Ovary (3.7)

Thyroid (2.7)

Other and unspecified (29.7)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM. GLOBOCAN 2008 v2.0, Cancer Incidence and Mortality Worldwide: IARC Cancer Base No.10 [Internet]. Lyon, France: International Agency for Research on

Cancer; 2010. Available from: http://globocan.iarc.fr, accessed on 06/06/2013. 2. American Cancer Society. Global Cancer Facts and Figures 2nd Edition. Atlanta: American Cancer Society; 2011.

Global cancer mortality

Both sexes Men Women0

5

10

15

20

25

Lung

Stomach

Liver

Colorectal

Female breastM

ort

ality

(%

of

all c

ance

r ty

pe

s)

Approximately 7.56 million people died from

cancer in 2008,1 accounting for 13% of all deaths (from any cause)2

Lung, stomach, liver, colorectal and female

breast cancers cause 50% of all cancer deaths1

Common terms

Localisedthe cancer is still confined to the site of origin and has

not yet invaded the surrounding tissues or spread to other sites

Invasivethe cancer has spread

from the site of origin into the surrounding tissues

Metastatic the cancer has spread to distant sites in the body to

form new tumours

Stage classification of the cancer,

important for treatment decisions, based on the

size, presence or absence of metastasis and involve-

ment of lymph nodes

Gradehow abnormal cancer cells appear in comparison to normal cells and how aggressive the cancer is

Low grade – nearly normal in appearance; slow rate of growth and metastasis

High grade – very abnormal-looking cells; high rate of growth and metastasis

Cancer categories

Carcinomacancer of the skin or tissues that line or cover the internal

organs

Sarcomacancer of bone,

cartilage, muscle, fat, blood vessels, and connective tissues

Leukaemia cancer of the bone

marrow affecting the white blood cells

Lymphoma cancer arising in the

lymph glands

Central nervous system cancerscancer of the brain or

spinal cord

Making sense of cancer names

Artwork originally created for the National Cancer Institute. Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.

Risk factor definitions

013

RISK FACTOR

Something that increases the chances of getting

a disease

Intrinsic risk factor

…is an integral part of the individual and

cannot be changed (genetics, age, etc.)

Extrinsicrisk factor

…is related to an individual’s own actions

and environment(tobacco, pollution,

diet, etc.)

Risk factors are multiple and differ according to the cancer type

RISK FACTORS

Age

ObesityBacteriaH.pylori

Hormones

Radiation

Diet

Smoking tobacco

General health

Hereditary

Chemicals

VirusesHPV

HBV

EBV

Sunexposure

Absolute risk vs. Relative risk

Absolute risk

The risk of an individual

developing cancer during

their entire lifetime

Relative risk

The risk of a group of people

developing cancer in

comparison to another group

Benefits of assessing risk

Allows the individual at risk to undertake prevention strategies (e.g. stop smoking, avoid radiation)!

Alerts physicians to those individuals at risk of developing cancer!

Early detection enables physicians to initiate treatment, whist the tumour is still in the initial stages!

Enables screening procedures to detect cancer at an early stage!

1. Nowell, PC. The clonal evolution of tumor cell populations. Science (1976) 194:23-28. 2. Cavenee, WK & White, RL. The genetic basis of cancer. Scientific American (1995) 272:72-79.

Emergence of a cancer cell

Malignant cell

Cancers originate from a single cell1,2

A series of mutations accumulate in successive generations of the cell in a process known as

clonal evolution

Eventually, a cell accumulates enough mutations to become

cancerousFirst

mutationSecond mutation

Third mutation

Fourth orlater mutation

Genetic mutations, i.e. changes to the normal base sequence of DNA, contribute to

the emergence of a cancer cell

In order for cancerous cells to develop and form a tumour, mutations and other alterations that allow the cell to acquire a succession of the

following biological capabilities must occur:1,2

The hallmarks of cancer

1. Hanahan D & Weinberg RA. The hallmarks of cancer. Cell (2000) 100:57-70. 2. Hanahan D & Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144:646-674

Sustaining proliferative signalling

Evading growth suppressors

Activating invasion & metastasis

Enabling replicative immortality

Inducingangiogenesis

Resisting cell death

Normal cells rely on positive growth signals from other cellsCancer cells can reduce their dependence on growth signals by:1,2

- Production of their own extracellular growth factors -- Overexpression of growth factor receptors -

- Alterations to intracellular components of signalling pathways -

Sustaining proliferative signalling

Cell wallIntracellular signalling

Growth factor receptors

Growth factors


• Normal cells rely on antigrowth signals to regulate cell growth1,2

• Cancer cells can become insensitive to these signals

• One way that this can happen is by disruption of the retinoblastoma protein (pRb) pathway1

• pRb prevents inappropriate transition from the G1 phase of the cell cycle to the synthesis (S) phase1

• In cancer cells, pRB may be damaged, allowing the cell to divide uncontrollably1

Celldivision

cycleG1

S

G2M


Evading growth suppressors

Resisting cell death

Hanahan D & Weinberg RA. The hallmarks of cancer. Cell (2000) 100:57-70. 2. National Cancer Institute, What is Cancer, 2010. 3. Hanahan D & Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144:646-674. Artwork originally created for

the National Cancer Institute. Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.

An important hallmark of many cancers is resistance to apoptosis,

which contributes to the ability of the cells to divide uncontrollably1,2

When normal cells become old/damaged, they go through

apoptosis (programmed cell death)

Normal celldivision

Cell damage –no repair

Apoptosis

Cancer celldivision

First mutation

Second mutation

Third mutation

Fourth orlater mutation

Uncontrolledgrowth

Another important hallmark of cancer is the ability of the cell to overcome the boundaries on how many times a cell can divide1

These limits are usually set by telomeres (the ends of chromosomes):1,2

• In normal cells, telomeres get shorter with each cell division until they become so short that the cell can no longer divide

• In cancer cells, telomeres are maintained, allowing the cell to divide an unlimited number of times

Enabling replicative immortality

Normal cells Cell division Cancer cells

Telomeres

No apoptosis

Apoptosis

Chromosomes


1.Folkman J. Clinical applications of research on angiogenesis. N Engl J Med (1995) 333:1757-63. 2. Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer (2008) 8:579-591.

Inducing angiogenesis

The formation and maintenance of new blood vessels (angiogenesis) plays a critical role in tumour growth.1,2

New blood vessels supply the cancer cells with oxygen and nutrients, allowing the tumour to grow.

Angiogenesis is mediated principally through vascular endothelial growth factor (VEGF)

Other growth factors also play a role, e.g.:

• Fibroblast growth factor (FGF)

• Platelet-derived growth factor (PDGF)

Nearby blood vessels grow into the tumour.

Oxygen and nutrients Blood vessel

Blood vessel

Pericyte

Endothelial

Smooth muscle

Cell wall

VEGFRFGFR PDGFR

Activating invasion & metastasis

1. Hanahan D & Weinberg RA. The hallmarks of cancer. Cell (2000) 100:57-70. 2. Gupta GP & Massagué J. Cancer metastasis: Building a framework. Cell (2006) 127: 679-695

Eventually, tumours may spawn pioneer cells that can invade adjacent tissues and

travel to other sites in the body to form new tumours

(metastasis)1

This capability allows cancerous cells to colonise

new areas where oxygen and nutrients are not

limiting1

Metastasis causes 90% of deaths from solid tumours2

Nearby blood vessels grow into the tumour.

Oxygen and nutrients

Cells escape and metastasiseBlood vessel

There is evidence that a further two emerging hallmarks are involved in the pathogenesis of cancer1

The acquisition of these hallmarks of cancer is made possible by two enabling characteristics1

Enabling characteristics and emerging hallmarks

1. Hanahan D & Weinberg RA. Hallmarks of cancer: the next generation. Cell (2011) 144:646-674

Evading immune destruction

Enabling characteristics

Genome instability and mutation

Deregulating cellular energetics

Tumour-promoting inflammation

Emerging hallmarksThe immune system is responsible for

recognising and eliminating cancer cells, and therefore preventing tumour

formation. Evasion of this immune surveillance by weakly immunogenic cancer cells is an important emerging

hallmark of cancer.

Cancer cells achieve genome instability by increasing their mutability, or rates

of mutation, through increased sensitivity to mutagenic agents or

breakdown of genomic maintenance machinery.

The uncontrolled growth and division of cancer cells relies not only on the

deregulation of cell proliferation, but also on the reprogramming of cellular

metabolism, including increased aerobic glycolysis (known as the

Warburg effect)

Immune cells infiltrate tumours and produce inflammatory responses, which

can paradoxically enhance tumourigenesis, helping tumours acquire the hallmarks of cancer

Click on each hallmark or enabling characteristic for more information

Diagnostic tests include:

• Physical examination

• Laboratory tests

• Imaging

• Endoscopic examination

• Biopsy

• Surgery

• Molecular testing

How is cancer diagnosed?

‘Cancer’ is an umbrella term for a broad group of diseases

There is no single test that can diagnose all cancers1

1. Stanford Cancer Institute, Cancer Diagnosis, 2012

If there are symptoms suggestive of cancer a broad range of tests allow HCPs to make an accurate and detailed diagnosis

Laboratory tests

Assess the general health of the body and levels of certain compounds

Typically, blood and/or urine samples

Blood is assessed for its composition, and can give an indication of liver and renal function

Blood, proteins and other compounds in the urine indicate there could be a problem

Tumour markers detected in blood or urine are substances created by the body in response to cancer cells

• Currently, markers are used to monitor treatment efficacy and recurrence

• May become more important in diagnosis in the future

1. Stanford Cancer Institute, Cancer Diagnosis, 2012.

CEA, carcinoembryonic antigen, several cancers can raise CEA levels; AFP, alpha-fetoprotein; HCG, human chorionic gonadotropin; CA 15-3 and CA 27-29 are most useful in assessing advanced breast cancer treatment

Marker Cancer

CA 125 Ovarian

CEA Colorectal

AFP Liver, ovarian, testicular

HCGTesticular, ovarian, liver,stomach, pancreatic, lung

CA 19-9 Colon, stomach, bile duct

CA 15-3 Ovarian, lung, prostate

CA 27-29Colon, stomach, kidney, lung, ovarian, pancreatic, uterus, and liver

Imaging


Produce images of the organs and structures

Reveal location and extent of disease

Three main types:

• Transmission imaging: high-energy photons beamed through body – the ‘opacity’ of different structures/tissues varies > X-ray, CT scan, bone scan, mammogram, lymphangiogram

• Reflection imaging: high frequency sound reflected differentially depending on structures/tissues > Ultrasound

• Emission imaging: atoms excited to emit energy waves detected by a scanner > MRI, PET

magnetic field direction

Imaging

Transmittedradio waves

Emittedradio waves

Endoscopy

1. Stanford Cancer Institute, Cancer Diagnosis 2012.

• BronchoscopyUsed to examine the airways and obtain tissue samples from the lungs

• Colonoscopy and sigmoidoscopyUsed to view the large intestine or just the sigmoid colon

• Endoscopic retrograde cholangiopancreatography (ERCP)Combined with X-ray to examine the liver, gallbladder, bile ducts, and pancreas

• Oesophagogastroduodenoscopy (upper endoscopy)Used to view the inside of the oesophagus, stomach, and duodenum

• Cystoscopy (cystourethroscopy)Device inserted through the urethra to examine the bladder and urinary tract

Oesophagus

Endoscope

Stomach

Light

Interior of stomach

Endoscope

Light

Stomachlining

Biopsy sample

An endoscope is a small, flexible tube with a light, lens and tools

Biopsy


Biopsy type Description

Endoscopic Tissue sample removed via an endoscopy

Bone marrow

Bone chip or cells aspirated from the sternum or hip

Excisional or incisional

Full thickness of skin even whole tumour removed

Fine needle aspiration (FNA)

Tiny pieces of tumour extracted via a thin needle

PunchShort cylinder of tissue taken

Shave Top layer of skin removed

Skin Small sample of skin taken

Tissue or cells from the body for examination under a microscope

Performed in the doctor’s office or hospital, depending on the type of biopsy and location of the tumour

Pathology

1. National Cancer Institute, Understanding Cancer, 2009.Artwork originally created for the National Cancer Institute.

Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.

Tests on biopsies and samples of patient tissue or body fluids reveal a great deal about the cancer

Microscopic examination can reveal the presence of cancer cells, the origin of the cancer cells (sub-type), and information on stage, etc.

Biopsy

Blood sampleor

tissue sample

Pathology

Proteomic profile

Genomic profile

What is TNM?

TNM is a system for classifying malignant tumours!

It is a cancer staging system, which describes the extent of a person's cancer!

Most medical facilities use this system as their main method for cancer reporting1!

Most types of cancer have TNM designations, but some do not1!

1. National Cancer Institute, Cancer Staging, 2010

How does the TNM system work?

The 3 parameters of the TNM system1:

T = extent of the tumour

N = the extent of spread to the lymph nodes

M = presence of distant metastases

A number is added to each letter

to indicate1:

the size or extent of the primary tumour

the extent of cancer spread


T = extent of primary tumour

organlocal tissues

T0 T1 T2 T3

T is classified as follows:1

Tx: Primary tumour cannot be evaluated | T0: No evidence of primary tumour

Tis: Carcinoma in situ (CIS)2 | T1, T2, T3, T4: Size and/or extent of the primary tumour

1. National Cancer Institute, Cancer Staging, 20102. CIS – abnormal cells are present but have not spread to neighbouring tissue; although not cancer, CIS

may become cancer and is sometimes called pre-invasive cancer

N = extent of spread to lymph nodes

distant nodes

local nodes

N0

N is classified as follows1:

Nx: Regional lymph nodes cannot be evaluated | N0: No local lymph node involvement

N1: Tumour has spread to local lymph nodes | N2, N3: Involvement of local and distant lymph nodes (number of lymph nodes and/or extent of spread)


N1 N2

M0

M = presence of distant metastases

M is classified as follows1:

Mx: Distant metastasis cannot be evaluated | M0: No distant metastasis

M1: Distant metastasis is present


bone

lung

liver

M1 Mx

?

Intrinsic vs. extrinsic factors

Cancer caused by intrinsic factors, i.e. inherited mutations, can only be prevented by screening and appropriate early intervention

Cancer Prevention

1. National Cancer Institute, Understanding Cancer, 2009.

Cancer caused by extrinsic factors can be prevented by reducing or eliminating exposure to these factors (e.g. chemicals, tobacco, radiation, viruses)

Radiation

Viruses or bacteria

Carcinogenicchemicals

Tobacco products

1. National Cancer Institute, Understanding Cancer, 2009. 2. WHO Fact Sheet 339, 2012.Artwork originally created for the National Cancer Institute.


The use of tobacco products is implicated in ~33% of all cancer deaths1

~1 person dies every 6 seconds due to tobacco2

The combination of tobacco and alcohol products appears to be particularly dangerous1

As well as lung cancer, tobacco products have also been implicated in cancer of the mouth, larynx, oesophagus, stomach, pancreas, kidney, and bladder1

Avoiding tobacco is the single most important factor in reducing cancer risk

Lung Cancer Risk Increases with Cigarette Consumption1

15x

10x

5x

0 15 30

LungCancerRisk

Cigarettes Smoked per DayNon-smoker

Excessive exposure to UV radiation

1. WHO Fact Sheet 305, 2009.

Excessive UV exposure, particularly in fair-skinned individuals can cause:1• cutaneous malignant

melanoma• squamous cell carcinoma• basal cell carcinoma

In 2000, >200,000 cases of melanoma were diagnosed worldwide1

Stratosphere

Sunexposure

Ozone

Epidermis

Dermis

Hypodermis

UV-A

UV-B

UV-C

Diet

National Cancer Institute, Understanding Cancer, 2009. Artwork originally created for the National Cancer Institute.


Unlike tobacco products, UV radiation and alcohol, dietary components that influence cancer risk have been difficult to determine1

Limiting fat and calorie intake appears to reduce cancer risk1

A diet rich in meat increases cancer risk, especially colon cancer1

Nu

mb

er o

f C

ases

(p

er 1

00,

00 P

eop

le)

Correlation Between Meat Consumption and Colon Cancer Rates in Different Countries1

40

30

15

Grams (per person per day)

N.Z.

20

10

0 80 100 200 300

U.S.A.

DEN. CANG.B.

SWENOR NETH

GERMANYICE

ISRJAMFIN P.R.

HUNGROM

COLNIG

JAPAN

YUG POL

CHILE

HPV Infection Increases Risk for Cervical Cancer2

Viruses

1. Liao JB. Viruses and Human Cancer. YJBM 2006 (79);115-122. 2.National Cancer Institute, Understanding Cancer, 2009. Artwork originally created for the National Cancer Institute. Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.

Worldwide, 15% of all cancers may be caused by viruses, including:1

• Epstein-Barr virus

• Human papilloma virus (HPV)

• Hepatitis B virus

• Human herpes virus-8

• Human T lymphotrophic virus type 1

• Hepatitis C virus

Reducing exposure to these viruses reduces cancer risk

In the case of HPV, avoiding unprotected sex with many partners reduces the risk of contracting this virus2

High

LowNon-infected

women

CervicalCancerRisk

Women infected with HPV

Strategies for prevention

about cancer and risk factors (warnings on cigarette packets, campaigns about sun and exposure to UV radiation)

pink ribbons for breast cancer, world cancer day

don’t smoke, stay out of the sun, avoid toxic chemicals and polluted areas

cervical smear, mammography, colonoscopy

HPV vaccine to reduce risk of cervical cancer; Hep B vaccine to reduce risk of liver cancer

normal weight, healthy diet, exercise

regular check-ups, seek medical attention early

Education

Awareness campaigns

Risk avoidance

Screening

Vaccines

Lifestyle

Healthcare

Breast Cancer Screening

What is screening?

Screening is the name given to a range of tests that can detect cancer at an early stage before symptoms appear

Finding cancer early usually means it is easier to treat/cure

By the time symptoms appear, the cancer may have grown and spread and therefore be more difficult to treat/cure

1. National Cancer Institute, Cancer Screening Overview, 2012.

Screening: the rationale

For screening to be effective, two requirements must be met:

A test or procedure must be available to detect cancers earlier than if the cancer were detected as a result of the development of symptoms

!

Evidence must be available that treatment initiated earlier as a consequence of screening results in an improved outcome

!

1. National Cancer Institute, Cancer Screening HCP, 2012.

Cervical Cancer Screening

Screening tests

National Cancer Institute, Cancer Screening Overview, 2012. Artwork originally created for the National Cancer Institute. Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.

A variety of tests are used in cancer screening:

• Physical exam and history: check general health and review medical history

• Laboratory tests: investigate samples of tissue, blood, urine, etc.

• Imaging: visualise the insides of the body using e.g. x-ray, ultrasound, CT, MRI, etc

• Molecular tests: look for specific mutations that are linked to some types of cancer

Biopsy

NormalPap smear

AbnormalPap smear

Patient‘s blood sampleor

tissue sample

Pathology

Proteomic profile

Genomic profile

Screening: pros and cons

Pros• Reduction in cancer deaths

• 3–35% of premature deaths due to cancer could be avoided with screening

• Improved outcomes (does not apply in all cases)

Cons• Some screening

procedures carry their own risks

• False negative results – patient wrongly assured there is no problem

• False positive results – patient may receive treatment they do not need

1. National Cancer Institute, Cancer Screening HCP, 2012.

Heredity and cancer

Screening and high risk populations

By focusing on high-risk populations, screening resources can be better applied

Patients with a personal history/strong family history of cancer are deemed to be high-risk

The ability to test for specific genetic mutations has further refined the identification of high-risk patients

National Cancer Institute, Cancer Screening HCP, 2012. Artwork originally created for the National Cancer Institute. Reprinted with permission of the artist, Jeanne Kelly. Copyright 2013.

All Breast Cancer Patients

Inherited factor(s) Other factor(s)

Genes and Cancer

RadiationViruses

Chemicals

Heredity

Chromosomesare DNA molecules

cancer the facts

Health & Medicine

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