1. Cancer Prevention and Screening
Mauricio Burotto MD
National Cancer Institute
National Institutes of Health

3. Rudolph Ludwig Karl Virchow

4. Virchow’s Accomplishment
Defined cancer as a disease involving uncontrolled cell growth
The initial description of leukemia
Defined cancer using a light microscope on specimens obtained on autopsy

5. Adenocarcinoma

6. Cancer is uncontrolled cell growth, uncontrolled mitoses

8. Virchow’s Accomplishments
The definition of cancer used in 2015 is largely that of Virchow with minor modifications More than 160 years later, we still use his definitions using a light microscope. There is clear evidence that some early detected cancers do not pose a threat and do not need to be treated

9. Hallmarks of Cancer

10. Different approches Integrative or complex perspective
For basic and translational cancer research
Operational perspective
For medical (public health, provider) intervention

11. Operational perspective

12. Operational perspective

13. Definitions Primary prevention Prevention
Secondary prevention Screening
Tertiary prevention Treatment

14. Concept Message
The number of new cancer cases is expected to rise by more than 50% in US and more than double worldwide by 2030, it is estimated that more than half of all cancers can be prevented by applying what we already know.

15. Prevention in Cancer Avoid exposures Interventions Tobacco Behavioral
Alcohol
Interventions
Behavioral
Decrease obesity
Pharmacological
Vaccines

16. Prevention in Cancer Avoid exposures Interventions Tobacco***
Alcohol
Interventions
Behavioral
Decrease obesity**
Pharmacological
Vaccine

17. Copyright 1964, U.S. Department of Health, Education, and Welfare

18. Copyright 1964, U.S. Department of Health, Education, and Welfare
Basis of more than 7,000 articles relating to smoking and disease already available at that time in the biomedical literature, the Advisory Committee concluded that smoking is:
A cause of lung and laryngeal cancer in men
A probable cause of lung cancer in women
The most important cause of chronic bronchitis
Copyright 1964, U.S. Department of Health, Education, and Welfare

19. Tobacco
Tobacco accounts for approximately one third of all cancer deaths, more than any other risk factor
Obesity is now the risk factor with the highest attributable cancer mortality (14% to 20%) after tobacco

23. Overweight and obesity By the evidence
Definitively associated with an increased risk of six cancers
Breast, CRC, Esophagus (ADC), Pancreas, Endometrial and RCC
Associated with increased death rates in
The same as before plus ovarian and prostate cancers

24. Diet modification and vitamins for cancer prevention

25. Diet and Cancer Prevention

26. Evidence in cancer prevention
Observational studies
More
Publication Bias to positives findings
Randomized studies
Less
Expensive
Longer follow-up

27. American Cancer Society Recommendations
Presented By Jeffrey Meyerhardt at 2014 ASCO Annual Meeting

28. Toxicity: What does it take to recognize small increases in risk
Toxicity: What does it take to recognize small increases in risk? -carotene
-ATBC
29,133 smokers
-CARET
18,314 at-risk
NEJM 330:1029, 1994

29. Prevention acting on infectious risk factor

30. Prevention acting on infectious risk factor

31. Approved agents for cancer chemoprevention

32. Approved agents for cancer chemoprevention

33. Ideal target for chemoprevention
Requires:
Abnormal level of expression in early, preinvasive human neoplasia relative to normal epithelium
Clear biological contribution to the initiation, maintenance, or progression of a preinvasive neoplasm to cancer

34. Ideal target for prevention
Pharmacologic accessibility :
Its modulation cause reductions in neoplastic incidence
Cancer mortality
Pathological evidence of improvement
Specificity for neoplasia, rather than the normal tissue from which cancers arise

35. Oral Oncology 2014

36. Effect of PPARγ Agonists on NSCLC: Treatment Animal Models (Lung)
-tumor volume ↓ 66.7%
-growth delay 104 days
Keshamouni et al. Oncogene 2004 36

37. Principles of Screening The basics

38. Cancer Screening
Screening is doing a test to determine if cancer might be present in an asymptomatic individual.
Diagnostic tests are used when there are symptoms to cause a clinical suspicion of disease.

39. Principles of Screening
Finding disease is not a measure of success in screening* Increased survival is not a legitimate measure of success outside of a randomized clinical trial Reduction of cancer specific mortality in a randomized trial is the only true proof of effective screening

40. Cancer Screening A series of tests with some uncertainties:
some known proven harms
some possible benefits
some proven benefits

41. Lead-time bias

42. Length Bias
Cancer diagnosed in between scheduled screens is more aggressive than those diagnosed at scheduled screenings. Those diagnosed at initial screening are least aggressive of all.

43. Screening Recommendations
By Cancer Site
Comments

44. Cancer Screening
Well designed clinical studies have consistently demonstrated the mortality reduction through:
Mammography for Breast Cancer
Stool Blood Testing, Sigmoidoscopy and Colonoscopy for Colorectal Cancer
Pap and Visual Screening for Cervical Cancer
Low Dose Spiral CT for those at high risk of Lung Cancer

45. Cervical Cancer

46. A Comment about Cervical Screening
American Cancer Society recommends annual cytological screening (Pap testing) beginning at age 21 and women who have three consecutive normal should be screened every three years. HPV testing is becoming common in US practices Visual Examination of the Cervix with Vinegar is effective especially in third world countries.

47. Colon Cancer

48. Colorectal Cancer Mortality 1975-2010
Age Adjusted Mortality Rate per 100,000
NCI SEER 2012

49. Colon Cancer Mortality
Decline due to:
Improvements in treatment
Screening with stool blood examination, sigmoidoscopy, colonoscopy
Awareness of symptoms and early presentation

50. Lung Cancer (NSCLC)

52. The National Lung Screening Trial
Nearly 54,000,
age 55 and above.
30 pack year or greater history of smoking. If quit, did so less than 15 years prior to trial entry.
Reasonable health.
Prospectively randomized to PA Chest Xray or Low Dose spiral CT yearly x 3.
Done at 30 sites with lung cancer expertise.
Analysis 10 years from start of screening showed 20% relative risk reduction.

53. The National Lung Screening Trial (one view of the 20 percent reduction in mortality)
Comparing the two groups (ten years from the start of screening)
80 to 90 lung cancer deaths were prevented in the screened group (87 less deaths).
About 350 still died of lung cancer.
16 died due to interventions caused by screening (six did not have cancer).

54. Science January 2015

55. “Here we show that the lifetime risk of cancers of many different types is strongly correlated (0.81) with the total number of divisions of the normal self-renewing cells”
“The majority is due “bad luck”, that is, random mutations arising during DNA replication of normal stem cells”
Science January 2015

57. What about cervix and gastric ???

59. Message
Avoiding exposures tobacco and “healthy life” are the most effective measure of cancer control
We are still learning which are the best screening methods
Which is better for US or Europe is not necessarily the best for our countries
Be critical about scientific and medical literature

60. Clinical Research Center
NCI-NIH
Clinical Research Center