8/13/2019 BCrisk.warren (1)
1/49
Diet, L ifesty le and
Breast Cancer Risk
Barbour S Warren, PhDProgram on Breast Cancer &Environmental Risk Factors
Sprecher Institute for Comparative CancerResearch
8/13/2019 BCrisk.warren (1)
2/49
- 0.6% of all cases are in men
- 216,600 NEW cases o f breas t cancer
and 40,200 deaths from breast can cer
- Inc idence - 110/10k peop le = 3 m il l ion in US
- L ifetim e risk is 13.48 % (1 in 7)
- 86% o f women w ith breast cancer are al ive
5 years after d iagno sis (76% alive at 10 years )
- Most common cancer (31%) in wom en
Scope o f Breast Cancer
8/13/2019 BCrisk.warren (1)
3/49
1) B iology o f the development o f
b reast cancer2) Risk facto rs for breast cancer (in
l igh t of the biology)
3) Poten t ial for mod if icat ion of b reast
cancer r isk
Overview
8/13/2019 BCrisk.warren (1)
4/49
Breas t Cancer ArisesFrom The In terac t ion o f
Two Processes
1) The Cancer Formation Process
2) The Process o f Developmento f the Breast
8/13/2019 BCrisk.warren (1)
5/49
Initiation Promotion ProgressionMutationCancer Gene
ProliferationIndependence
MutationInvade Spread
Stages of Cancer Formation
UnspecializedCell
InitiatedCell BenignTumor
MalignantTumor
Latency Period, 20 years or more
8/13/2019 BCrisk.warren (1)
6/49
Breas t Cancer ArisesFrom The In terac t ion o fTwo Processes
1) The Cancer Formatio n Process
2) The Process o f Developmento f th e Breast
8/13/2019 BCrisk.warren (1)
7/49
Development o f the Breast Ductal TreeDifferent iat ion Occurs With Pregnancy
2 yearsAfter
Puberty
After
Pregnancy
Proli feration Prol i ferationDifferentiation
Prol i feration
Bir th
8/13/2019 BCrisk.warren (1)
8/49
Prol i ferat ion
Differentiat ion
Prol i ferat ion and Different iat ion
A Ying -Yang Relat ionship in B reast Cancer Form ation
8/13/2019 BCrisk.warren (1)
9/49
Proliferation Cell MultiplicationEssential for normal growth developmentof the breastImportant factor in breast cancer
Allows less time for mutation repairThe key event during tumor promotion
8/13/2019 BCrisk.warren (1)
10/49
Cancer Gene
DNA
Carc inogen
Low
Prol i ferat ion
Normal
Canc er Gene
High
Prol i ferat ion
Permanent ly Mutated
Cancer Gene
Proliferation Decreases Mutation Repair
Time ForRepair Before
DNADuplication
Little TimeFor RepairBefore DNADuplication
Within a Cell
In Each Daugh ter Cell In Each Daug hter Cell
8/13/2019 BCrisk.warren (1)
11/49
Proliferation Cell MultiplicationEssential for normal growth developmentof the breastImportant factor in breast cancer Decreases time for mutation repair
Estrogen and other reproductive hormonescause proliferation of breast cells
Key event during the tumor promotionProliferating cells at risk to undergo initiation,promotion and progression stages of cancerformation
8/13/2019 BCrisk.warren (1)
12/49
Prol i ferat ion
Differentiat ion
Prol i ferat ion and Different iat ion
A Ying -Yang Relat ionship in B reast Cancer Form ation
8/13/2019 BCrisk.warren (1)
13/49
Development o f the Breast Ductal TreeDifferent iat ion Occurs With Pregnancy
2 yearsAfter
Puberty
After
PregnancyBir th
Lobules
8/13/2019 BCrisk.warren (1)
14/49
PubertySexual
Matur i tyPregnancy Lactat ion
TerminalEnd Bud
Lobu leType 1
Lobu leType 2
LobuleTyp e 3
LobuleTyp e 4
60 22 4 1
Level of Prol i ferat ion
Different iat ion of A Breast Lobule
Growth to a Func t ioning Ent ity
8/13/2019 BCrisk.warren (1)
15/49
B reas t Lo bu le Types
Puberty
Pregnancy
Lactat ion
Lobule
Ty pe 2
Lobule
Type 3
Lobule
Type 4
Lobu le
Typ e 1
Cont ains cel ls at
to become breast cancer
h ighes t r is k
- c ells t ha t are
- c ells t ha t are
prol i ferat ing
not d i f ferent iated
Premenopausal Women Have
Dif ferent Lob ule Types
80%-100% type 3 lo bul esChildbearing
30%-35% ty pe 2 lob ules
5%-10% type 3 lob ules
Childless
50%-60% type 1 lobul es
8/13/2019 BCrisk.warren (1)
16/49
Key B iologic al Facto rs for
B reas t Cancer Risk
1) Number of to become
br east tumo rs
- Cells which are not d iffer entiated - Cells which are p ro li ferat ing
Cel l s at Risk
2) and o ther hormo nes
- Levels of th ese horm ones in blood
- Level of recept ors for these hormones
Estrogen
Cel ls Suscept ib l e toBecome Tumors
- Measure of to cancervulnerabi l i ty
8/13/2019 BCrisk.warren (1)
17/49
Cel ls at Risk A re Analogous
to a Targets Bulls-eye
Cellsat
Risk
Cells
at
Risk
Cells
at
Risk
Carcinogens
A larger num ber of cells at r isk p rodu ces a larger
(and easier to hit) bulls-eye.
8/13/2019 BCrisk.warren (1)
18/49
In terac t ion o f a Cel l at Riskw i th a Carcinogen Can Produce
an In it iated Cell
An ini t iated cel l is the first s tep
in format ion o f a tumor
For an ini t iated cel l to become a
tumo r both the Promot ion and
Progression s tages have to
occur
The larger the num ber of
ini t iated cel ls th e higher the
breast cancer r isk
Cells
at
Risk
8/13/2019 BCrisk.warren (1)
19/49
P u b er t y
M e n arc h e M e n o p a u s e P re g n a n c y
Ch i l d b i r t h B i r t h
A g e
Events During A Wom ans Lifetime
Num
bero
fCe
llsa
tRisk
To
Become
Bre
as
tTumors
L i f et im e C h a n g e s i n N um b e r o f
C e l l s a t R i s k to B e c om e B r e as t Tum o r s
i n a T h eo re t i c a l C h i l d b ea r in g Wo m a n
8/13/2019 BCrisk.warren (1)
20/49
P u b er t y
M e n arc h e M e n o p a u s e P re g n a n c y
Ch i l d b i r t h B i r t h
A g e
Events During A Wom ans Lifetime
Num
bero
fCe
llsa
tRisk
To
Become
Bre
as
tTumors
L i f et im e C h a n g e s i n N um b e r o f
C e l l s a t R i s k to B e c om e B r e as t Tum o r s
i n a T h eo re t i c a l C h i l d b ea r in g Wo m a n
8/13/2019 BCrisk.warren (1)
21/49
P u b er t y
M e n arc h e M e n o p a u s e P re g n a n c y
Ch i l d b i r t h B i r t h
A g e
Events During A Wom ans Lifetime
Num
bero
fCe
llsa
tRisk
To
Become
Bre
as
tTumors
L i f et im e C h a n g e s i n N um b e r o f
C e l l s a t R i s k to B e c om e B r e as t Tum o r s
i n a T h eo re t i c a l C h i l d b ea r in g Wo m a n
8/13/2019 BCrisk.warren (1)
22/49
P u b er t y
M e n arc h e M e n o p a u s e P re g n a n c y
Ch i l d b i r t h B i r t h
A g e
Events During A Wom ans Lifetime
Num
bero
fCe
llsa
tRisk
To
Become
Bre
as
tTumors
L i f et im e C h a n g e s i n N um b e r o f
C e l l s a t R i s k to B e c om e B r e as t Tum o r s
i n a T h eo re t i c a l C h i l d b ea r in g Wo m a n
8/13/2019 BCrisk.warren (1)
23/49
P u b er t y
M e n arc h e M e n o p a u s e P re g n a n c y
Ch i l d b i r t h B i r t h
A g e
Events During A Wom ans Lifetime
Num
bero
fCe
llsa
tRisk
To
Become
Bre
as
tTumors
L i f et im e C h a n g e s i n N um b e r o f
C e l l s a t R i s k to B e c om e B r e as t Tum o r s
i n a T h eo re t i c a l C h i l d b ea r in g Wo m a n
8/13/2019 BCrisk.warren (1)
24/49
P u b er t y
M e n arc h e M e n o p a u s e P re g n a n c y
Ch i l d b i r t h B i r t h
A g e
Events During A Wom ans Lifetime
Num
bero
fCe
llsa
tRisk
To
Become
Bre
as
tTumors
L i f et im e C h a n g e s i n N um b e r o f
C e l l s a t R i s k to B e c om e B r e as t Tum o r s
i n a T h eo re t i c a l C h i l d b ea r in g Wo m a n
8/13/2019 BCrisk.warren (1)
25/49
P u b er t y
M e n arc h e M e n o p a u s e P re g n a n c y
Ch i l d b i r t h B i r t h
A g e
Events During A Wom ans Lifetime
Num
bero
fCe
llsa
tRisk
To
Become
Bre
as
tTumors
L i f et im e C h a n g e s i n N um b e r o f
C e l l s a t R i s k to B e c om e B r e as t Tum o r s
i n a T h eo re t i c a l C h i l d b ea r in g Wo m a n
8/13/2019 BCrisk.warren (1)
26/49
P u b er t y
M e n arc h e M e n o p a u s e P re g n a n c y
Ch i l d b i r t h B i r t h
A g e
Events During A Wom ans Lifetime
Num
bero
fCe
llsa
tRisk
To
Become
Bre
as
tTumors
L i f et im e C h a n g e s i n N um b e r o f
C e l l s a t R i s k to B e c om e B r e as t Tum o r s
i n a T h eo re t i c a l C h i l d b ea r in g Wo m a n
8/13/2019 BCrisk.warren (1)
27/49
8/13/2019 BCrisk.warren (1)
28/49
P u b e r t y
M e n a r c h e M e n o p a u s e B i r t h
A g e
E v e n t s D u rin g A W o m a n s L ife ti m e
N
um
bero
fCellsa
tRisk
To
Become
Breas
tTumors
L i f e t i m e C h a n g e s i n N u m b e r o f
C e l l s a t R i s k t o B e c o m e B r e a s t T u m o r s
in a T h e o r e t i c a l C h i l d l e s s W o m a n
8/13/2019 BCrisk.warren (1)
29/49
Key Bio log ical Facto rs for
B reas t Cancer Risk
1) Number of to become
br east tumo rs
- Cells which are not d ifferentiat ed - Cells which are p ro li ferat ing
Cel l s at Risk
2) and o ther hormones
- Levels of th ese horm ones in blood
- Level of recept ors for these ho rmones
Estrogen
Cells Susceptib le toBecome Tumor s
- Measure of to cancervulnerabi l i ty
8/13/2019 BCrisk.warren (1)
30/49
Estrogen
Estrogen acts w i th other reproduct ive to
inc rease pro l i ferat ion in the breast
Prol i ferat ion is l inked to: Tumor promo t ion
Decreased mu tat ion repair
Increases in the number of cells at risk
Estrogen may be metabo l ized to form a
carc inogen which could cause mutat ions and
form ini t iated cel ls
Relat ion to B reast Cancer Risk
8/13/2019 BCrisk.warren (1)
31/49
Estrogen
How Is The Risk Of
Breas t Cancer Increased?
1) Larger number of mu tat ions
Increased ini t iat ion & progressio n
2) Greater level of p ro l i ferat ionIncreased promot ion & progression
3) Inc rease number of cells at r isk to
become breast cancer
4) Inc rease the t ime of h igh risk
for tumor in i t iat ion
8/13/2019 BCrisk.warren (1)
32/49
Age Related>- Age ( 50 vs 30 vs < 20 yr )
Reprod uct ion Related
>
- Age of menarche (
8/13/2019 BCrisk.warren (1)
33/49
Establ is hed Risk Factors
for B reas t Cancer
Enviro nment Related- Exp osure to ion izing radiation
Breast D isease
- Breast B iopsy (any f inding)
- Atypi cal hyperp lasia
Relative RiskRisk Facto r
1.0 - 8.7
1.5 - 1.8
4.0 - 4.4
8/13/2019 BCrisk.warren (1)
34/49
Vegetables and Fruits
Eating large amounts of vegetables, in general,may be l inked to a small decrease in b reast
cancer r isk
Supp lements do no t appear to o f fer the
same protect ion as food
Evidence is stronger for a decrease in r isk
w ith dark g reen and yel low vegetables
Eating fru i t , in general, is unrelated to b reast
cancer r isk
Vegetables may have a greater effect fo r
women wi th a fam i ly h is tory of b reast cancer
8/13/2019 BCrisk.warren (1)
35/49
Ant i -cancer Agents in Vegetables & Frui ts
Inh ibi t ion of Ini t iat ion Stage of Cancer Formation
8/13/2019 BCrisk.warren (1)
36/49
Initiation Promotion ProgressionMutationCancer Gene
ProliferationIndependence
MutationInvade Spread
Stages of Cancer Formation
UnspecializedCell
InitiatedCell BenignTumor
MalignantTumor
Latency Period, 20 years or more
8/13/2019 BCrisk.warren (1)
37/49
Ant i -cancer Agents in Vegetables & Frui ts
Inh ibi t ion of Ini t iat ion Stage of Cancer Formation
A) Block carcinogen act ivat ion
Flavono ids and iso f lavono ids
Coumar ins
Iso thioc yanates in cruc i ferou s vegetables
Organosul fur compounds in gar lic & onions
B) Enhance carcinogen detoxi f icat ion
An t ioxidants in plants
Iso thioc yanates in cruc i ferou s vegetables
Organosul fur compounds in garl ic & onions
C) Increase DNA repair
Polypheno ls in green tea
Selenium
8/13/2019 BCrisk.warren (1)
38/49
Initiation Promotion ProgressionMutationCancer Gene
ProliferationIndependence
MutationInvade Spread
Stages of Cancer Formation
UnspecializedCell
InitiatedCell BenignTumor
MalignantTumor
Latency Period, 20 years or more
8/13/2019 BCrisk.warren (1)
39/49
Ant i -cancer Agents in Frui ts & VegetablesInhibition of Promotion Stage of CancerFormation
A) Scavenge reactive oxygen species Antioxidants in plants
B) Alter proliferation differentiation Phytoestrogens (+/-) Retinoids
8/13/2019 BCrisk.warren (1)
40/49
Phytoestrogens
- Exposure befo re puberty m ay b e necessary for
a pro tect ive effect
- Estrog en-l ike ch emicals in p lan ts
- Soy produc ts
High levels of ph ytoestrogens
Most studi ed ph ytoestrogens
- Stud ies of soy and breast cancer r isk in
A sian popu lat ion are conf l ic t ing
- Concern vo iced because o f estro gen -l ike effects
- A rea o f high interest
8/13/2019 BCrisk.warren (1)
41/49
Whole Grains and Fiber
- A small decr ease in breast c ancer r isk has
been assoc iated with eat ing who le grains
- A small decr ease in b reast c ancer r isk
may be associated w ith dietary f iber
- 4 of 5 co hort no assoc iat ion
- 11 o f 14 case-c ont ro l small d ecrease
- Small decreases in tumo rs in anim als- Effects on c irculat ing est rogens unclear
8/13/2019 BCrisk.warren (1)
42/49
Meat and Fish
- As so ciat ion of eat ing poul t ry and breastcanc er r is k is unclear
- Eat ing m eat may be associated w ith in cr easedrisk o f breast c ancer
- Women wh o eat red meat may have a h igher
inc idence of breast cancer
- Most s tudies saw no asso ciat io n between
eating f ish and b reas t cancer r isk
- Studies examin ing m ethod s of cookin g anddoneness show a relat ion ship to b reast
canc er r is k
8/13/2019 BCrisk.warren (1)
43/49
Dairy Produc ts
- Dairy p rodu cts co ntain conj ugated lin ole ic
acid (CLA) which dec reases mammary tumorformation in rats
- Studies examining dairy product consumpt ion
and b reast cancer r is k are con f l ict ing
- Stud ies of ch ildh ood and ado lesc entconsumpt ion of dai ry products and
b reas t cancer r is k are also conf l ict ing
8/13/2019 BCrisk.warren (1)
44/49
Dietary Fat
Con trad ictory f ind ings
- Pos i t ive as sociat ion (inc reased r isk )
Ecologi cal stud ies, Animal stud ies
- Inc onc lusive assoc iat ion
Case-con trol stud ies of women
- No asso ciat ionCoho rt s tudies of women
8/13/2019 BCrisk.warren (1)
45/49
Physical Act iv i ty
May be associated w ith decreased breast cancer
r isk for women of all ages
Though t to poss ib ly act by changing:1)Mens trual act iv i ty
Exercise may increase age at menarche
2) Body character is t ics
Exerc ise can decrease body fat3) Hormone levels
Exercise may decrease estro gen levels
8/13/2019 BCrisk.warren (1)
46/49
Smok ing Tobacco
Effect o f adu l t smok ing (act ive & passive) is
unclear
Age beginn ing sm oking m ay be impo r tant
Heavy smokers below age 20 have a30% to 80% increase in b reast cancer
r isk
Cigaret te smoke contains numerous
chemical wh ich can in i tiate and promotecancer
Breast f lu ids o f smokers con tain
chemicals f rom cigaret te smoke
8/13/2019 BCrisk.warren (1)
47/49
A lcoho l Use
Adul t use asso ciated with r isk (about 10%
inc rease for each d rink per day) A ll stu dies have repo rted impact of early age
alcoho l use on b reast cancer r isk
About tw ice the r isk o f breast cancer for wom en
below 35 years
Alco hol u se increases estrogen levels
Adequate fol ic acid (B v itamin) may decrease risk
in women who have mo re than 1 dr ink per day
8/13/2019 BCrisk.warren (1)
48/49
Obesi ty
Associated w ith decreased premenopausal
breast cancer risk (25% decrease)
Inter feres w ith regular menstrual cycl ing
Less p rol i ferat ion in breast Assoc iated wi th inc reased postmenopausal
breast cancer risk (about 200% increase)
Inc reases estro gen exposure
Fat cells form estrogen from other hormones
8/13/2019 BCrisk.warren (1)
49/49
Initiation PromotionMutationCancer Gene
ProliferationIndependence
Modifying the Stages of Cancer Formation
UnspecializedCell
InitiatedCell
BenignTumor
Decrease Init iat ion Pro cess
1) Minimize Exposures
2) Chi ldbir th
3) Diet
Decrease cells at risk
1) Chi ldb ir th2) Diet?
Elimin ate Init iated Cells
1) Chi ldb ir th?2) Diet?
Decrease Promotion Process
1) Decrease est rogen ic exposures
2) Chi ldb ir th
3) Diet