Risk factors for Breast Cancer Risk factors for Breast Cancer

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  • 1. Diet, Lifestyle andBreast Cancer Risk Barbour S Warren, PhD Program on Breast Cancer &Environmental Risk Factors Sprecher Institute for Comparative CancerResearch

2. 3. 1) Biology of the development of breast cancer 2) Risk factors for breast cancer (in light of the biology) 3) Potential for modification of breast cancer risk Overview 4. 5. Initiation Promotion Progression

  • Proliferation
  • Independence

Stages of Cancer Formation Unspecialized Cell Initiated Cell Benign Tumor Malignant Tumor Latency Period, 20 years or more

  • Mutation
  • Cancer Gene
  • Mutation
  • Invade & Spread

6. 7. Development of the Breast Ductal Tree Differentiation Occurs With Pregnancy 2 years AfterPuberty After Pregnancy Proliferation Proliferation Differentiation Proliferation Birth 8. Proliferation and Differentiation A Ying-Yang Relationship in Breast Cancer Formation Proliferation Differentiation 9. Proliferation Cell Multiplication Essential for normal growth & development of the breast Important factor in breast cancer

  • Allows less time for mutation repair
  • The key event during tumor promotion

10. Proliferation Decreases Mutation Repair Time For Repair Before DNA Duplication Little Time For Repair Before DNA Duplication Within a Cell In Each Daughter Cell In Each Daughter Cell 11. Proliferation Cell Multiplication Essential for normal growth & development of the breast Important factor in breast cancer

  • Decreases time for mutation repair

Estrogen and other reproductive hormones cause proliferation of breast cells

  • Key event during the tumor promotion

Proliferating cells at risk to undergo initiation, promotion and progression stages of cancer formation 12. Proliferation and Differentiation A Ying-Yang Relationship in Breast Cancer Formation Proliferation Differentiation 13. Development of the Breast Ductal Tree Differentiation Occurs With Pregnancy 2 years AfterPuberty After Pregnancy Birth Lobules 14. Puberty Sexual Maturity Pregnancy Lactation Terminal End Bud Lobule Type 1 Lobule Type 2 Lobule Type 3 Lobule Type 4 60 22 4 1 Level of Proliferation Differentiation ofABreast Lobule Growth to a Functioning Entity 15. 16. 17. Cells at Risk Are Analogousto a Targets Bulls-eye

  • A larger number of cells at risk produces a larger (and easier to hit) bulls-eye.

Carcinogens 18. Interaction of a Cell at Riskwith a Carcinogen Can Producean Initiated Cell

  • An initiated cell is thefirst stepin formation of a tumor
  • For an initiated cellto become a tumorboththe Promotion and Progression stages have to occur
  • Thelargerthe number of initiated cells thehigherthe breast cancer risk

19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. Estrogen

  • Estrogen acts with other reproductive to increase proliferation in the breast
  • Proliferation is linked to:
  • Tumor promotion
  • Decreased mutation repair
  • Increases in the number of cells at risk

Estrogen may be metabolized to form a carcinogen which could cause mutations and form initiated cells Relation to Breast Cancer Risk 31. How Is The Risk OfBreast Cancer Increased?

  • Larger number ofmutations
  • Increased initiation & progression

2) Greater level ofproliferation Increased promotion & progression 3) Increase number ofcells at riskto become breast cancer 4) Increase thetime of high riskfor tumor initiation 32. 33. 34. Vegetables and Fruits

  • Eating large amounts of vegetables, in general, may be linked to a small decrease in breast cancer risk
  • Supplements do not appear to offer the same protection as food
  • Evidence is stronger for a decrease in risk with dark green and yellow vegetables
  • Eating fruit, in general, is unrelated to breast cancer risk
  • Vegetables may have a greater effect for women with a family history of breast cancer

35. Anti-cancer Agents in Vegetables & Fruits Inhibition of Initiation Stage of Cancer Formation 36. Initiation Promotion Progression

  • Proliferation
  • Independence

Stages of Cancer Formation Unspecialized Cell Initiated Cell Benign Tumor Malignant Tumor Latency Period, 20 years or more

  • Mutation
  • Cancer Gene
  • Mutation
  • Invade & Spread

37. Anti-cancer Agents in Vegetables & Fruits Inhibition of Initiation Stage of Cancer Formation

  • Block carcinogen activation
    • Flavonoids and isoflavonoids
    • Coumarins
    • Isothiocyanates in cruciferous vegetables
    • Organosulfur compounds in garlic & onions
  • Enhance carcinogen detoxification
    • Antioxidants in plants
    • Isothiocyanates in cruciferous vegetables
    • Organosulfur compounds in garlic & onions
  • C) Increase DNA repair
    • Polyphenols in green tea
    • Selenium

38. Initiation Promotion Progression

  • Proliferation
  • Independence

Stages of Cancer Formation Unspecialized Cell Initiated Cell Benign Tumor Malignant Tumor Latency Period, 20 years or more

  • Mutation
  • Cancer Gene
  • Mutation
  • Invade & Spread

39. Anti-cancer Agents in Fruits & Vegetables Inhibition of Promotion Stage of Cancer Formation

  • Scavenge reactive oxygen species
    • Antioxidants in plants
  • Alter proliferation & differentiation
    • Phytoestrogens (+/-)
    • Retinoids

40. 41. 42. 43. 44. 45. Physical Activity

  • May be associated with decreased breast cancer risk for women of all ages
  • Thought to possibly act by changing:
  • Menstrual activity
  • Exercise may increase age at menarche
  • 2) Body characteristics
  • Exercise can decrease body fat
  • 3) Hormone levels
  • Exercise may decrease estrogen levels

46. Smoking Tobacco

    • Effect of adult smoking (active & passive) is unclear
    • Age beginning smoking may be important
      • Heavy smokers below age 20 have a 30% to 80% increase in breast cancer risk
      • Cigarette smoke contains numerous chemical which can initiate and promote cancer
      • Breast fluids of smokers contain chemicals from cigarette smoke

47. Alcohol Use

    • Adult use associated with risk (about 10% increase for each drink per day)
    • All studies have reported impact of early age alcohol use on breast cancer risk
    • About twice the risk of breast cancer for women below 35 years
    • Alcohol use increases estrogen levels
    • Adequate folic acid (B vitamin) may decrease risk in women who have more than 1 drink per day

48. Obesity

    • Associated withdecreasedpremenopausal breast cancer risk (25% decrease)
      • Interferes with regular menstrual cycling
      • Less proliferation in breast
    • Associated withincreasedpostmenopausal breast cancer risk (about 200% increase)
      • Increases estrogen exposure
      • Fat cells form estrogen from other hormones

49. Initiation Promotion

  • Proliferation
  • Independence

Unspecialized Cell Initiated Cell Benign Tumor Decrease Initiation Process 1) Minimize Exposures 2) Childbirth 3) Diet 4) Avoid radiation exposure

  • Decrease cells at risk
  • Childbirth
  • Diet?
  • Eliminate Initiated Cells
  • Childbirth?
  • Diet?
  • Decrease Promotion Process
  • Decrease estrogenic exposures
  • Childbirth
  • Diet
  • Physical Activity
  • Mutation
  • Cancer Gene

Modifying the Stages of Cancer Formation