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
Department of SurgeryDivision of Public Health Sciences
No Relevant Financial Relationships with Commercial Interests
Graham A. Colditz, MD DrPH
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
Department of SurgeryDivision of Public Health Sciences
Edwards, et al. Cancer 2002
Projected number of cases, USA
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
What PotentiallyInfluences Cancer?
Macro-level factorscrime
povertyavailability of services
Demographic factorsage
genderancestry
Genetic factorstelomere lengthInherited mutationssporadic mutations
Individual-level factorsdiet
health behaviors
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
What are the causes of cancer in society and which ones can be prevented?
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
Time course: lung & total mortalityCurrent smoker:continuing
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
Department of SurgeryDivision of Public Health Sciences
Source: New York Times, 2012
Department of SurgeryDivision of Public Health Sciences
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
Department of SurgeryDivision of Public Health Sciences
Source: Institute of Medicine, Accelerating Progress in Obesity Prevention, 2012
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
Model of breast cancer evolutionWellings-Jensen Model (JNCI 55:231, 1975)
Time (decades)
TDLUADH DCIS IBC
GrowthCCH
s Adhesion& Polarity Diversity
Invasion
LCIS
ALH
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
Lifestyle: high income countriesCause % cancer
causedMagnitude possible reduction
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
Department of SurgeryDivision of Public Health Sciences
Lifestyle: high income countriesCause % cancer
causedMagnitude possible reduction
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
Department of SurgeryDivision of Public Health Sciences
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+
Department of SurgeryDivision of Public Health Sciences
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.
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
Breast Cancer:Multiple birth model
Rosner, Colditz, Willett, Am J Epidemiology 1994;139:826
9% /yr
2.5% /yr
Menarche First birth Menopause
Department of SurgeryDivision of Public Health Sciences
Norway
Finland
Sweden
Change in age at menarche
Department of SurgeryDivision of Public Health Sciences
Change in menarche, Korea
Cho Eur J Pediatr 2009
30 years
Department of SurgeryDivision of Public Health Sciences
Trends in Fertility
Calendar year Ito et al NEBR, 2008
Department of SurgeryDivision of Public Health Sciences
Mean age at first birth OECD, 2009
Department of SurgeryDivision of Public Health Sciences
Breast Cancer Incidence, Korea
1998 4o, born 19582008 40, born 1968
Jung et al, J Breast Ca, 2011
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
Lewington Int J Epi 2014
Age at menarche, China
Department of SurgeryDivision of Public Health Sciences
Lewington Int J Epi 2014
Parity, China
Department of SurgeryDivision of Public Health Sciences
Lewington Int J Epi 2014
Age at first birth, China
Department of SurgeryDivision of Public Health Sciences
Department of SurgeryDivision of Public Health Sciences
Model of breast cancer evolutionWellings-Jensen Model (JNCI 55:231, 1975)
Time (decades)
TDLUADH DCIS IBC
GrowthCCH
s Adhesion& Polarity Diversity
Invasion
LCIS
ALH
Department of SurgeryDivision of Public Health Sciences
Adolescent fiber & BBD: NHSII
Su et al, Cancer Causes Control, March 2010
Department of SurgeryDivision of Public Health Sciences
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.
Department of SurgeryDivision of Public Health Sciences
-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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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
Department of SurgeryDivision of Public Health Sciences
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:
Department of SurgeryDivision of Public Health Sciences
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