Reshaping cancer care through genomics: current challenges and

future opportunities

David ThomasDirector, The Kinghorn Cancer Centre

Head, Cancer Division

Garvan Institute of Medical Research

The burden of cancer in Australia

• Incidence– 2009: 114,137 new cases of cancer (excluding non-melanoma skin cancer)

• 2013: predicted 124,910 • 2020: predicted 149,990

– 1 in 2 men; 1 in 3 women– 1982-2009: cancer incidence doubled

• Mortality– 2010: 42,844 deaths– 3 in 10 total deaths– 1 in 4 men; 1 in 6 women– Overall 5 year survival is 66.1% (2006-10)

• Community burden– 2012: leading cause of disease burden– 551,300 years of healthy life lost

http://canceraustralia.gov.au/affected-cancer/what-cancer/cancer-australia-statistics

AIHW, Australia’s Health 2010; John Goss, 2008, Projected Australian health care expenditure 2003-2032

Cancer and GDP

GDP on track for 286 billion in 2032/33, 12.4% of GDP

Cancer accounts for 19% of disease burden, 29% of deaths and 7.2% of health expenditure

Projected cancer expenditure in 2032/33 $10.1 billion

The cancer journey

Prevention Diagnosis Death

Survivorship

Treatment

100,000s 10,000s 1,000s

Co

mm

un

ity

The cancer journey

Prevention Diagnosis Death

Survivorship

Treatment

100,000s 10,000s 1,000s

Co

mm

un

ity

Diagnostic (r)evolution

Stephen Fox

7

Heatmap of mutations

Cancer 2015; Stephen Fox, Andrew Fellowes

Rare & less common cancers

• Individual incidence of 6-12 per 100,000 Australians

• In 2009, 42,000 diagnoses in Australia

• 22,000 deaths (45% of all cancer deaths)

– 25% under age 50

• 12.6% of research funding

• No progress in survival 1990-2009

Personalized medicine

Tsimberidou et al J Clin Oncol 29: 2011 (suppl; abstr CRA2500)

Personalized medicine

Tsimberidou et al J Clin Oncol 29: 2011 (suppl; abstr CRA2500)

100

90

80

70

60

50

40

30

20

10

0

Pro

gre

ssio

n-f

ree s

urv

ival

(%)

No. of patients in follow up

Dacarbazine

Vemurafenib

0 1 2 3 4 5 6 7 8 9 10 11 12

Hazard Ratio 0.26

(95% CI; 0.20 - 0.33)

Log-rank P<0.0001

Months

274

275

213

268

85

211

48

122

28

105

16

50

10

35

6

16

3

4

0

3

Dacarbazine

(N=274)

Vemurafenib (N=275)

Progression-free survival

Median 1.6 mos Median 5.3 mos

The cancer journey

Prevention Diagnosis Death

Survivorship

Treatment

100,000s 10,000s 1,000s

Co

mm

un

ity

Cancer is curable if detected early

Cancer risk is not random

Knowing your cancer risk

Clinically identified risk

Genomically identified risk

Familial cancer patterns

Referral patterns at the Peter Mac Familial Cancer Centre

0

500

1000

1500

2000

2500

3000

2009/10 2011/12 2010/11 2012/13 2013/14

Other

Bowel cancer

Breast cancer

The Angelina Jolie effect

Genetic architecture of cancer risk

0

10

20

30

40

50

60

1 2 4 6 10

Pop

ula

tio

n a

llele

fre

qu

en

cy

Relative risk

FGFR2CASP8

PTENPALB2

ATMCHEK2

TP53, BRCA1/2, RB1

Genetic architecture of cancer risk

0

10

20

30

40

50

60

1 2 4 6 10

Pop

ula

tio

n a

llele

fre

qu

en

cy

Relative risk

FGFR2CASP8

PTENPALB2

ATMCHEK2

TP53, BRCA1/2, RB1

GWAS

Genetic architecture of cancer risk

0

10

20

30

40

50

60

1 2 4 6 10

Pop

ula

tio

n a

llele

fre

qu

en

cy

Relative risk

FGFR2CASP8

PTENPALB2

ATMCHEK2

TP53, BRCA1/2, RB1

GWAS

Family linkage

Fraction of explained heritable risk

Orli Bahcall | doi:10.1038/ngicogs.1

Breast

Ovarian

Prostate

Combined data on 44,788 pairs of mono- and dizygotic twins from the Swedish, Danish, and Finnish twin registries to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer

Clinically identified risk= 5-10% of cancers

Genomically identified risk= 10-25% of cancers

= 15,000-35,000 Australians in 2020

Knowing your cancer risk

Whole genome sequencing

1.8 Terabases/3d run(= 16 human genomes)

US$1000/genome

“It is a major human accomplishment on par with the development of the telescope or the microprocessor. If there was any doubt to if genomics would ever be able to reach the everyday man, at this price point and efficiencies it is absolute certainty.”

Michael Schatz, Cold Spring Harbor Laboratory, Nature, 15 January 2014

Cancer burden in Australia

Prostate(C61)

Colorectal(C18–C20)

Lung,bronchus&trachea(C33–C34)

Melanomaofskin(C43)

Lymphoma(C81–C85,C96)

Unknownprimarysite(C26,C39,C76–C80)

Bladder(C67)

Leukaemia(C91–C95)

Kidney(C64)

Stomach(C16)

Other

Breast(C50)

Colorectal(C18–C20)

Melanomaofskin(C43)

Lung,bronchus&trachea(C33–C34)

Lymphoma(C81–C85,C96)

Uterus,body(C54)

Unknownprimarysite(C26,C39,C76–C80)

Ovary(C56)

Thyroid(C73)

Leukaemia(C91–C95)

Other

Females Males

Inci

den

ceM

ort

alit

yPo

ten

tial

yea

rs o

f lif

e lo

st

Genetic architecture of cancer risk

0

10

20

30

40

50

60

1 2 4 6 10

Pop

ula

tio

n a

llele

fre

qu

en

cy

Relative risk

FGFR2CASP8

PTENPALB2

ATMCHEK2

TP53, BRCA1/2, RB1

GWAS

Family linkage

PopulationWES/WGS

Genomics and more efficient and cost-effective cancer care

Tabar et al., Lancet, 2003

Lancet, 2012

Lancet, 2014

Genomics and more efficient and cost-effective cancer care

Lower than average risk

Paul James

Cost of mammographic screening

• In Australia, all women 50-74 years of age should receive mammograms every 2 years

• $141/woman in breast screen (2006/7 data)• 900,000 women screened in 2008• Total cost of BreastScreen Australia = $120M in

2006/7• If 10% women with the lowest cancer risk were

not screened it would save $10M– Later start date?– Or not as frequently?