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Diet, Lifestyle and Breast Cancer Risk. Barbour S Warren, PhD Program on Breast Cancer & Environmental Risk Factors Sprecher Institute for Comparative Cancer Research. Overview. 1) Biology of the development of breast cancer 2) Risk factors for breast cancer (in light of the biology)

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slide1

Diet, Lifestyle and

Breast Cancer Risk

Barbour S Warren, PhD

Program on Breast Cancer & Environmental Risk Factors

Sprecher Institute for Comparative Cancer Research

slide3

Overview

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

slide5

Mutation

  • Invade & Spread
  • Mutation
  • Cancer Gene

Latency Period, 20 years or more

Malignant

Tumor

Unspecialized

Cell

Initiated

Cell

Benign

Tumor

Promotion

Progression

Initiation

  • Proliferation
  • Independence

Stages of Cancer Formation

slide7

Development of the Breast Ductal Tree

Differentiation Occurs With Pregnancy

After

Puberty

After

Pregnancy

Birth

2 years

Proliferation

Differentiation

Proliferation

Proliferation

slide8

Proliferation

Differentiation

Proliferation and Differentiation

A Ying-Yang Relationship in Breast Cancer Formation

slide9

Proliferation – Cell Multiplication

Essential for normal growth & development of the breast

Important factor in breast cancer

  • The key event during tumor promotion
  • Allows less time for mutation repair
slide10

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

slide11

Proliferation – Cell Multiplication

Essential for normal growth & development of the breast

Important factor in breast cancer

  • Decreases time for mutation repair
  • Key event during the tumor promotion

Proliferating cells at risk to undergo initiation, promotion and progression stages of cancer formation

Estrogen and other reproductive hormones cause proliferation of breast cells

slide12

Proliferation

Differentiation

Proliferation and Differentiation

A Ying-Yang Relationship in Breast Cancer Formation

slide13

Development of the Breast Ductal Tree

Differentiation Occurs With Pregnancy

After

Puberty

After

Pregnancy

Birth

2 years

Lobules

slide14

Differentiation of A Breast Lobule

Growth to a Functioning Entity

Sexual Maturity

Pregnancy

Lactation

Puberty

Terminal End Bud

Lobule

Type 1

Lobule

Type 2

Lobule

Type 3

Lobule

Type 4

Level of Proliferation

60

22

4

1

slide17

Carcinogens

Cells at Risk Are Analogous

to a Target’s Bull’s-eye

  • A larger number of cells at risk produces a larger (and easier to hit) bull’s-eye.
slide18

Interaction of a Cell at Risk

with a Carcinogen Can Produce

an Initiated Cell

  • An initiated cell is the firststep in formation of a tumor
  • For an initiated cell to become a tumor both the Promotion and Progression stages have to occur
  • The larger the number of initiated cells the higher the breast cancer risk
estrogen
Estrogen

Relation to Breast Cancer Risk

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

slide31

How Is The Risk Of

Breast Cancer Increased?

  • Larger number of mutations
  • Increased initiation & progression

2) Greater level of proliferation

Increased promotion & progression

3) Increase number of cells at risk to become breast cancer

4) Increase the time of high risk for tumor initiation

slide34

Vegetables and Fruits

  • Eating large amounts of vegetables, in general, may be linked to a small decrease in breast cancer risk
  • Evidence is stronger for a decrease in risk with dark green and yellow vegetables
  • Vegetables may have a greater effect for women with a family history of breast cancer
  • Eating fruit, in general, is unrelated to breast cancer risk
  • Supplements do not appear to offer the same protection as food
slide35

Anti-cancer Agents in Vegetables & Fruits

Inhibition of Initiation Stage of Cancer Formation

slide36

Mutation

  • Invade & Spread
  • Mutation
  • Cancer Gene

Latency Period, 20 years or more

Malignant

Tumor

Unspecialized

Cell

Initiated

Cell

Benign

Tumor

Promotion

Progression

Initiation

  • Proliferation
  • Independence

Stages of Cancer Formation

slide37

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
slide38

Mutation

  • Invade & Spread
  • Mutation
  • Cancer Gene

Latency Period, 20 years or more

Malignant

Tumor

Unspecialized

Cell

Initiated

Cell

Benign

Tumor

Promotion

Progression

Initiation

  • Proliferation
  • Independence

Stages of Cancer Formation

slide39

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
slide45

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
smoking tobacco
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
alcohol use
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
obesity
Obesity
  • Associated with decreased premenopausal breast cancer risk (25% decrease)
    • Interferes with regular menstrual cycling
    • Less proliferation in breast
  • Associated with increased postmenopausal breast cancer risk (about 200% increase)
    • Increases estrogen exposure
    • Fat cells form estrogen from other hormones
slide49

Mutation

  • Cancer Gene

Modifying the Stages of Cancer Formation

  • Decrease cells at risk
  • Childbirth
  • Diet?
  • Eliminate Initiated Cells
  • Childbirth?
  • Diet?

Benign

Tumor

Initiated

Cell

Unspecialized

Cell

Initiation

Promotion

  • Proliferation
  • Independence

Decrease Initiation Process

1) Minimize Exposures

2) Childbirth

3) Diet

4) Avoid radiation exposure

  • Decrease Promotion Process
  • Decrease estrogenic exposures
  • Childbirth
  • Diet
  • Physical Activity