Diet, Lifestyle and

1
Diet, Lifestyle and Breast Cancer Risk
Barbour S Warren, PhD Program on Breast Cancer
Environmental Risk Factors Sprecher Institute
for Comparative Cancer Research
2
(No Transcript)
3
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
4
(No Transcript)
5
Latency Period, 20 years or more
Malignant Tumor
Unspecialized Cell
Initiated Cell
Benign Tumor
Promotion
Progression
Initiation

• Proliferation
• Independence

Stages of Cancer Formation
6
(No Transcript)
7
Development of the Breast Ductal
Tree Differentiation Occurs With Pregnancy
After Puberty
After Pregnancy
2 years
Birth
Proliferation Differentiation
Proliferation
Proliferation
8
Proliferation and Differentiation A Ying-Yang
Relationship in Breast Cancer Formation
9
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

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

• 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
12
Proliferation and Differentiation A Ying-Yang
Relationship in Breast Cancer Formation
13
Development of the Breast Ductal
Tree Differentiation Occurs With Pregnancy
After Puberty
After Pregnancy
2 years
Birth
Lobules
14
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
15
(No Transcript)
16
(No Transcript)
17
Cells at Risk Are Analogous to a Targets
Bulls-eye

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

18
Interaction of a Cell at Risk with a Carcinogen
Can Produce an Initiated Cell

• An initiated cell is the first step 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

19
(No Transcript)
20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
(No Transcript)
25
(No Transcript)
26
(No Transcript)
27
(No Transcript)
28
(No Transcript)
29
(No Transcript)
30
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
31
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
32
(No Transcript)
33
(No Transcript)
34
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

35
Anti-cancer Agents in Vegetables Fruits
Inhibition of Initiation Stage of Cancer Formation
36
Latency Period, 20 years or more
Malignant Tumor
Unspecialized Cell
Initiated Cell
Benign Tumor
Promotion
Progression
Initiation

• Proliferation
• Independence

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

• Proliferation
• Independence

Stages of Cancer Formation
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
(No Transcript)
41
(No Transcript)
42
(No Transcript)
43
(No Transcript)
44
(No Transcript)
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 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

49

• 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