carpe diem: time to seize the opportunity for cancer prevention

Carpe Diem: Time to Seize the Opportunity for Cancer

Prevention

Graham A. Colditz, MD, DrPHASCO: June 1, 2014

Department of SurgeryDivision of Public Health Sciences


No Relevant Financial Relationships with Commercial Interests

Graham A. Colditz, MD DrPH


Goals of talkFocus = future and potential for preventionLocal and global burdenReview obstacles to prevention

• Skepticism cancer can be prevented• Societal factors adding to complexity of prevention• Time frame

Breast cancer example to integrateTools and support to move forward

Online tools and resources http://tinyurl.com/l4a4g2j

http://tinyurl.com/l4a4g2j




Aging US population Over 65 rising from 13% in 2012 to more than 20% of pop. in 2050

Cancer burden• Assume incidence per 100,000 holds steady at

each age• Number of new cancer cases will double by 2050

simply due to aging population


Edwards, et al. Cancer 2002

Projected number of cases, USA


Estimated new cancer cases, World, 1975 to 2050: Region

Bray and Moller Nat Rev Cancer 2006

New Cases

2012 already at 14M new cases diagnosed


Global burden, 2012

14 million new cases of cancer diagnosed

7.4M men; 6.6M women

1.7 Million new cases of breast cancer

25% of all cancer diagnosed in womenGlobocan 2012, IARC


Cancer careCost – billions ($US 125b in 2010)Breast cancer: $US 16.6 b, or 13% in 2010• 36% of this cost in the last year of life

Increasing burden direct and indirect costs of cancerLost productivity due to breast cancer $US 10.9b• Competition among drug manufacturers,

surgical, radiation oncology, etc• What are system perspectives and patient

perspectives? Hassett & Elkin, 2013


United States: New cases, women, 2014

Cancer New CasesBreast 232,670Lung 108,210 50%Colorectal 65,000 Uterus 52,630Lymphoma 36,650Thyroid 47,790Melanoma 32,210Kidney 24,780Ovary 21,980TOTAL 810,320

Cancer Facts and Figures, 2014


Why aren’t we preventing cancer now?

Multiple barriers:• Skepticism that cancer can be prevented• Short term focus of cancer research• Interventions deployed too late in life• Research focused on treatment not prevention• Debates among scientists• Societal factors ignored• Lack of transdisciplinary training • Complexity of implementation

Colditz et al Sci Transl Med 2012: March 28http://tinyurl.com/l4a4g2j



Why aren’t we preventing cancer now?Multiple barriers:• Skepticism that cancer can be prevented• Short term focus of cancer research

Colditz et al Sci Transl Med 2012: March 28http://tinyurl.com/l4a4g2j



Overcoming obstacles of skepticism and time frame • Must counter skepticism that cancer can

be prevented Arguments about endpoints of prevention: risk

marker, premalignant lesion, invasive disease, death

Avoid exposure vs. remove later in life Can we intervene if we don’t have the

pathway defined?• Take into account time frame of cancer

development


What PotentiallyInfluences Cancer?

Macro-level factorscrime

povertyavailability of services

Demographic factorsage

genderancestry

Genetic factorstelomere lengthInherited mutationssporadic mutations

Individual-level factorsdiet

health behaviors


Public health benefitsLie in the future

Beneficiaries generally unknown

Public has no idea what public health programs do. Thus, when people benefit from prevention they don’t recognize they have been helped

Opposition to public health approaches that require societal change

Hemenway D. Why we don’t spend enough on public health. NEJM 2010


What are the causes of cancer in society and which ones can be prevented?


Trends in smoking and lung cancer, USA

0

1000

2000

3000

4000

5000

1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000Year

0

20

40

60

80

100

Num

ber o

f cig

aret

tes

per c

apita

Lung

can

cer d

eath

rate

per

100

,000Cigarette consumption

Lung cancerMen

Lung cancerwomen


Time course: lung & total mortalityCurrent smoker:continuing


Preventing Cancer: Tobacco• Killed 100 million people globally in last

century• Projected to kill 1 billion by end of this

century• Causes at least 11 different types of cancer• Yet, single biggest public health success

story of past 50 years• Smoking rates in United States more than

cut in half since 1964.• Nearly 20% of people in US still smoke


Source: New York Times, 2012


Preventing Cancer

• Work toward an “Endgame”• Maintain and expand current tobacco

control polices• Initiate innovative new policies• Continue to promote and support

cessation• Regulate electronic cigarettes as

tobacco products

Tobacco - Approaches


Source: Institute of Medicine, Accelerating Progress in Obesity Prevention, 2012


Preventing Cancer

• Provide reimbursement and incentives for better integrating weight counseling into primary care delivery

• Improve access to high-quality food in communities, schools, and workplaces

• Improve education and self-efficacy on healthy weight issues

• Create infrastructure and surroundings that support physical activity

Overweight & Obesity - Approaches


Why aren’t we preventing cancer now?Multiple barriers:• Skepticism that cancer can be prevented• Short term focus of cancer research

Ignores decades-long time course for cancer development

Colditz et al Sci Transl Med 2012: March 28


Model of breast cancer evolutionWellings-Jensen Model (JNCI 55:231, 1975)

Time (decades)

TDLUADH DCIS IBC

GrowthCCH

s Adhesion& Polarity Diversity

Invasion

LCIS

ALH


Lifestyle: high income countriesCause % cancer

causedMagnitude possible reduction

Time (yrs)

Smoking 33Overweight/obesity

20

Diet 5Lack of exercise

5

Occupation 5Viruses 5-7Family history 5Alcohol 3UV/ionizing radiation

2

Reproductive 3Pollution 2

Colditz, Wolin, Gehlert. Sci Trans Med 2012




Time (yrs)

Smoking 33 75%Overweight/obesity

20 50%

Diet 5 50%Lack of exercise

5 85%

Occupation 5 50%Viruses 5-7 100%Family history 5 50%Alcohol 3 50%UV/ionizing radiation

2 50%

Reproductive 3 0Pollution 2 0




Time (yrs)

Smoking 33 75% 10-20Overweight/obesity

20 50% 2-20

Diet 5 50% 5-20Lack of exercise

5 85% 5-20

Occupation 5 50% 20-40Viruses 5-7 100% 20-40Family history 5 50% 2-10Alcohol 3 50% 5-20UV/ionizing radiation

2 50% 2-10

Reproductive 3 0 N/APollution 2 0 N/A


Medical interventions proven to prevent cancer

Intervention Target Magnitude of reduction

Time (yrs)

Aspirin Colon mortality 40% 20+SERMs Breast incidence 40-50% 5+Salpingo oophorectomy

Familial breast ca 50% 3+

Screening for colorectal ca

Colon ca mortality 30-40% 10

Viruses Cervical ca incidence

50-100% 20+

Liver ca incidence 70-100% 20+Mammography Breast ca mortality 30% 10-20Serial CT lung Lung ca mortality 20% 6+


Time course of benefits:Cost effectiveness considerationsUniversal Hepatitis B vaccination saves lives and dollars through reducing sequalae of infection• Primary prevention saves dollars!

Hung, Taiwan 2009 China data show same benefit, extend life & save

dollars, Lu 2013

• Hung and Chen. Vaccine 2009;27:6770-6• Lu SQ, et al. Vaccine 2013;31:1864– 1869

The Value of Childhood Vaccination:Benefits Accrue across Time

Health gains

Health care cost savings

Care-related productivity gains

Outcome-related productivity gains

Behavior-related productivity gains

Community externalities

Time since VaccinationNarrow

BroadImproved outcomes in unvaccinated community members

Improvement of child health and survival changes household behavior

Increased productivity due to improved cognition, physical strength, and school attainment

Parents’ productivity increases because need to take care of sick child is avoided

Savings of medical expenditures because illness is prevented

Reduction in morbidity and mortality

Scop

e of

ben

efits

Adapted from Barnighausen, T., et al. "Accounting for the full benefits of childhood vaccination in South Africa: SAMJ forum." South African Medical Journal 98.11 (2008): 842-844.


What works: beyond smoking cessation and vaccines?• ACS guidelines NPA:

not overweight, eat a plant based diet, limit alcohol, be active

• Avoid alcohol between adolescence and first birth

Reduced cancer incidence by: • Breast 22% • Colon 52%Reduced mortality

Thomson et al 2014

• Reduce premalignant and invasive breast cancer

Liu Y, et al JNCI 2013


Breast Cancer incidence:Pike model – Nature 1983

To accommodate the higher incidence with late first birth, we add a constant representing an increase in risk with FFTP (+b) in figure

Pike, et al. Nature 1983


Breast Cancer:Multiple birth model

Rosner, Colditz, Willett, Am J Epidemiology 1994;139:826

9% /yr

2.5% /yr

Menarche First birth Menopause


Norway

Finland

Sweden

Change in age at menarche


Change in menarche, Korea

Cho Eur J Pediatr 2009

30 years


Trends in Fertility

Calendar year Ito et al NEBR, 2008


Mean age at first birth OECD, 2009


Breast Cancer Incidence, Korea

1998 4o, born 19582008 40, born 1968

Jung et al, J Breast Ca, 2011


Risk factors account for 76% discrepancy China vs. USA• Compared age specific incidence in Shanghai

prospective cohort vs. SEER.• Then fit Rosner-Colditz model to account for risk

factors Age at menarche, age at first and subsequent births, height,

weight at 18 and through adult life, alcohol, menopause, type of menopause (natural, surgical), use of postmenopausal hormone therapy (E alone, E+P), benign breast disease, family history breast ca.

• 76% of the US excess incidence controlled away with the established risk factors.

• Leaves 24% not included in our modelsLinos,…,Colditz JNCI 2008;100:1352-60


Lewington Int J Epi 2014

Age at menarche, China



Parity, China



Age at first birth, China


Model of breast cancer evolutionWellings-Jensen Model (JNCI 55:231, 1975)

Time (decades)

TDLUADH DCIS IBC

GrowthCCH

s Adhesion& Polarity Diversity

Invasion

LCIS

ALH


Adolescent fiber & BBD: NHSII

Su et al, Cancer Causes Control, March 2010


Ontario, Canada: Population-based case-control study

Recall of adolescent diet (55 food items)

High participation (2865 cases, 3299 controls)

Top vs. bottom quintile of intake Fiber mvOR = 0.66 (0.55 - 0.78) Vegetable protein mvOR = 0.80 (0.68 – 0.95) Nuts mvOR = 0.76 (0.61 - 0.95)

Liu, Y., et al. (2014). Adolescent Dietary Fiber, Vegetable Fat, Vegetable Protein, and Nut Intakes and Breast Cancer Risk. Breast Ca Res Treat.


-13%Regular physical activity

-25%Having children (4)

-18%Avoiding alcohol

-16%Breast feeding

No children Breast Cancer Risk ReductionStarting in Early Life

Risk

Ac

cum

ulat

ion

Births(20, 23, 26, 29)

Menopause

Age

10 20 30 40 50 60 70

Colditz and Bohlke 2014


Children (4) No chil

dren No post-menopausal

hormones

Physical activity No alcohol

Medications to lower risk (for high risk women)

Healthy weight Average woman – overweight

Obesity

Breast Cancer Risk ReductionStarting in Mid Life

Risk

Ac

cum

ulat

ion

Births(20, 23, 26, 29)

MenopauseAge

10 20 30 40 50 60 70

Colditz & Bohlke 2014


Using data to guide and sustaining social change• Common agenda• Shared measurement system• Mutually reinforcing activities• Continuous communication and• A backbone support organization

Kania et al 2011 Stanford Social Innovation Review

Delivering Prevention

Through policy – federal, state, local, hyperlocal

Through health care providers Through social norms and interactions Through community engagement Through individuals


Implementing prevention

“Plan A” should be prevention and early detection

“Plan B” (therapy) should be necessary only when plan A fails

But we need to implement Plan A!--Vogelstein, Science, 2013

http://tinyurl.com/l4a4g2j Online tools and resources:



Source: USDHHS 2004, 2006, 2012. Note: The condition in red is a new disease that has been causally linked to smoking in this report.

SG 2014

carpe diem: time to seize the opportunity for cancer prevention

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