Contents Allocating Cancer-Directed Expenditures: Tensions Between Prevention, Early Detection and Treatment is Unnecessary

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1 Contents 1 Allocating Cancer-Directed Expenditures: Tensions Between Prevention, Early Detection and Treatment is Unnecessary Bruce E. Hillner and Thomas J. Smith 1.1 Introduction Our Life Expectancy and Cancer Success Stories No Cure in Sight: Costs of Drugs, Gadgets, Genomics and Technology Bending the Cancer Cost Curve Conclusion... 8 References Lessons Learned from Prevention Programs: Different Endpoints Should Be Used in Secondary and Tertiary Prevention Franz Porzsolt 2.1 Introduction Methods Results Traditional Outcomes of Treatment and of Prevention Programs Proposal for the Evaluation of Prevention Programs Discussion The Risk of Interpretation in Prevention Programs The Resulting Need for Evaluation of Preventive Medicine Recommendations for Future Preventive Research References v

2 vi Contents 3 Biomarkers for Early Detection and as Surrogate Endpoints in Cancer Prevention Trials: Issues and Opportunities Barbara K. Dunn, Karin Jegalian, and Peter Greenwald Abbreviations Biomarkers: What They Are and How They Are Applied Screening Biomarkers for Early Detection Biomarkers as Surrogate Endpoints in Cancer Prevention Trials Breast Precancer and Cancer Prevention Ductal Carcinoma In situ Tissue Stroma and Mammographic Density Biomarkers, ER-Positive Breast Cancer, and Breast Cancer Prevention Trials Biomarkers and Estrogen Receptor-Negative Breast Cancers Access to Breast Tissue for Biomarker Evaluation Biomarkers in Phase 2 Chemoprevention Trials Prostate Cancer Prevention PSA Screening and Early Detection of Prostate Cancer Phase 3 Prostate Cancer Prevention Trials Discovery of New Biomarkers for Early Detection of Prostate Cancer Colorectal Cancer Prevention Lung Cancer Prevention Molecular Markers for Early Detection and Prognosis Treating Nicotine Addiction Fluorescence Bronchoscopy Conclusions References Targeting Polyamines and Inflammation for Cancer Prevention Naveen Babbar and Eugene W. Gerner 4.1 Introduction Polyamines, Inflammation, and Cancer Polyamine Metabolism Polyamines and Cancer Roles of Inflammation and Polyamines in Prostate Cancer Polyamines and Prostate Cancer Polyamines, Inflammation, and Prostate Cancer Targeting Polyamines and Inflammation in Prostate Cancer Roles of Inflammation and Polyamines in Colon Cancer Polyamines and Colon Cancer Polyamines, Inflammation, and Colon Cancer Targeting Polyamines and Inflammation in Colon Cancer... 56

3 Contents vii 4.5 Roles of Inflammation and Polyamines in Other Cancers Conclusions References Thinking About the Role (Largely Ignored) of Heavy Metals in Cancer Prevention: Hexavalent Chromium and Melanoma as a Case in Point Frank L. Meyskens and Sun Yang 5.1 Background The Evolution of the Idea Substances That Bind Melanin Major Risk Factors for Cutaneous Melanoma Epidemiology Metals Chemistry and Genetic Damage Chromium Chemistry Upregulation of Metallothioneins (MTs) Some Preliminary Experimental Data Future Prospects References Hepatitis B Virus and Cancer Prevention Mei-Hwei Chang 6.1 Infection and Cancer Disease Burden of Liver Cancer Hepatitis B Virus Infection and Hepatocellular Carcinoma Cancer Prevention Against Hepatocellular Carcinoma Hepatitis B Vaccination Program Effective Reduction of Chronic HBV Infection by Universal Hepatitis B Immunization The Effect on Liver Cancer Prevention by Vaccination Problems and Strategies of Successful HCC Prevention by Hepatitis B Vaccination Implications and Future Prospects References Chemoprevention of Hepatocellular Carcinoma in Chronic Hepatitis C Timothy R. Morgan 7.1 Hepatitis C Hepatocellular Carcinoma Prevention of Hepatocellular Carcinoma Curative Treatment... 87

4 viii Contents Treatments That Suppress Hepatitis C Virus Noncurative Chemoprevention Prospective Randomized Trials: Carotenoids and Phytochemicals Secondary Chemoprevention of HCC Nonrandomized, Uncontrolled and/or Retrospective Clinical Trials Epidemiologic Studies Drugs Used to Treat Hepatocellular Carcinoma Prevention of Hepatocellular Carcinoma in Cell Lines and Animal Models Phase II Trial of S-Adenosylmethionine in Hepatitis C Cirrhosis Conclusions References Nutritional Aspects of Primary Prostate Cancer Prevention Hans-Peter Schmid, Claus Fischer, Daniel S. Engeler, Marcelo L. Bendhack, and Bernd J. Schmitz-Dräger 8.1 Introduction Dietary/Nutritional Factors Dietary Fat Obesity Micronutrients Vitamins Minerals Phytoestrogens Diabetes Mellitus American Cancer Society (ACS) Guideline A: Try to Maintain a Healthy Weight B: Take Regular Physical Exercise C: Maintain a Healthy Diet with a Focus on Fruit and Vegetables D: Reduce Alcohol Intake Conclusions References Prostate Cancer Prevention with 5 Alpha-Reductase Inhibitors Dipen J. Parekh 9.1 Rationale for the Chemoprevention of Prostate Cancer The Prostate Cancer Prevention Trial Pathologic Characteristics of the Cancers in the Prostate Cancer Prevention Trial

5 Contents ix 9.4 Finasteride Increases Sensitivity of Prostate-Specific Antigen, Digital Rectal Examination and Biopsy Detection for Prostate Cancer Decreased Prostate Volume with Finasteride Increases Cancer Detection Side Effects of Finasteride Conclusion References Hormone Replacement Therapy and Breast Cancer Anthony Howell and Gareth D. Evans 10.1 Background HRT Use in Women Diagnosed with Breast Cancer Observational Studies Randomised Trials Effects of Withdrawal of HRT in Women with Breast Cancer HRT and Risk of Breast Cancer Observational Studies Randomised Studies Withdrawal of HRT in Women Without Breast Cancer Summary HRT After Oophorectomy in Women Less Than 50 Years of Age Observational Studies Coronary Heart Disease Potential Biological Explanations Conclusions References Physical Activity and Breast Cancer: Review of the Epidemiologic Evidence and Biologic Mechanisms Christine M. Friedenreich 11.1 Epidemiologic Evidence Background Methodologic Issues in Studies of Physical Activity and Cancer Overall Associations Between Physical Activity and Breast Cancer Risk Type, Dose, and Timing of Activity Population Subgroups Summary of Epidemiologic Findings Biologic Mechanisms Adiposity Sex Hormones

6 x Contents Insulin-Related Factors Adipokines and Inflammation Other Mechanisms Conclusion References Prevention of Breast Cancer by Newer SERMs in the Future Trevor Powles 12.1 Introduction Arzoxifene Lasofoxifene Discussion Conclusions References Chemoprevention of Hormone Receptor-Negative Breast Cancer: New Approaches Needed Iván P. Uray and Powel H. Brown 13.1 Introduction Endocrine Preventive Agents Selective Estrogen Receptor Modulators Aromatase Inhibitors New Strategies to Prevent Hormone-Independent Breast Cancer PARP Inhibitors Cell Growth Inhibitors Statins Metformin Retinoids PPAR Agonists COX-2 Inhibitors Tyrosine Kinase Inhibitors The IGF System Conclusions and Future Directions References

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