1.
Risk factors for Breast Cancer
The role of genetics
Professor Tarek Tawfik Amin
Public Health
Cairo University
amin55@myway.com

2.
Introduction
o A risk factor isanything that affectsthechance
of getting adisease, such ascancer.
o About 70% of women diagnosed with BC did
not haveknown risk factors.
o It ishard to definethecontribution of different
risk factorsin thedevelopment of BC.
o Multiplicity of risk factorsincreasethe
likelihood for diseasedevelopment.

3.
Breast cancerrisk factors
Menses
menopause
Dense breast
tissue
Aging
Personal
Breast cancer
Benign breast
Lesions
Family history
Genetics
Gender
Breast cancer
Physical
Inactivity
Obesity
Alcohol
Radiotherapy
HR
Therapy
Oral
contraception
Breast
feeding
Having
children
Breast
Cancer
Non-modifiable ModifiableControversial /uncertain
Personal behavioral,
environmental
Anti
prespirants
Anti
prespirants
BrasBras
Induced
abortion
Induced
abortion
Breast
implants
Breast
implants
TobaccoTobacco
Night
work
Night
work
Diet
vitamins
Diet
vitamins
Enviro.
chemicals
Enviro.
chemicals

4.
Non-modifiable risk factors
Gender
o Simply being awoman isthemain risk factor
for developing breast cancer (BC).
o BC isabout 100 timesmorecommon among
women than men.
o Breast cellsareconstantly exposed to the
growth-promoting effectsof thefemale
hormonesestrogen and progesterone.

5.
Non-modifiable risk factors
Aging
o Therisk of developing breast cancer increases
with age.
o About 1 out of 8 invasivebreast cancersare
found in women < 45.
o About 2 of 3 invasivebreast cancersarefound
in women age55 or older.

6.
Non-modifiable risk factors
Genetic risk factors
o About 5% to 10% of breast cancer casesare
thought to behereditary, resulting directly
from genedefects(called mutatio ns) inherited
from aparent.

7.
Genes in breast cancer
BRCA1 and BRCA2 mutations:
o Themost common causeof hereditary breast cancer.
o In normal cells, thesegeneshelp prevent cancer by
making proteinsthat keep thecellsfrom growing
abnormally.
o Inheritanceof amutated genesincreasetherisk for BC.
o Therisk may beashigh as80% for membersof some
familieswith BRCA mutations. Cancerstend to occur in
younger women and moreoften affect both breasts, with
increased risk for developing other cancers(ovarian).
o BRCA mutationsarefound most often in Jewish women
of Ashkenazi (Eastern Europe) origin, but they can occur
in any racial or ethnic group.

8.
Genes
• BRCA1: A geneon chromosome17 that normally
helpsto suppresscell growth. A person who inherits
certain mutations(changes) in aBRCA1 genehasa
higher risk of getting breast, ovarian, prostate, and
other typesof cancer.
• BRCA2: A geneon chromosome13 that normally
helpsto suppresscell growth. A person who inherits
certain mutations(changes) in aBRCA2 genehasa
higher risk of getting breast, ovarian, prostate, and
other typesof cancer.

9.
Genes in breast cancer

10.
Changes in othergenes:
 Thesegenemutationsaremuch rarer and often do not increasetherisk
of breast cancer asmuch astheBRCA genes.
 They arenot frequent causesof inherited breast cancer.
ATM:
TheATM genenormally helpsrepair damaged DNA. Inheriting 2
abnormal copiesof thisgenecausesthediseaseataxia-telangiectasia.
Inheriting onemutated copy of thisgenehasbeen linked to ahigh rateof
breast cancer in somefamilies.
p53:
Inherited mutationsof thep53 tumor suppressor genecausethe Li-
Fraumeni syndro me.
Peoplewith thissyndromehavean increased risk of developing breast
cancer, aswell asseveral other cancerssuch asleukemia, brain tumors, and
sarcomas.
Genes in breast cancer

11.
Genes in breast cancer

12.
Genes in breast cancer
CHEK2:
TheLi-Fraumeni syndromecan also becaused by
inherited mutationsin theCHEK2 gene.
Inheritanceof mutated CHEK2 can increasebreast
cancer risk of about twofold.
PTEN:
ThePTEN genenormally helpsregulatecell growth.
Inherited mutationscause Co wden syndro me, arare
disorder with increased risk for both benign and
malignant breast tumors, tumorsof thedigestivetract,
thyroid, uterus, and ovaries.

13.
Genes in breast cancer
CDH1:
Inherited mutationsin thisgenecause hereditary
diffuse gastric cancer.
Women with mutationsin thisgenealso havean
increased risk of invasivelobular breast cancer.
STK11:
Defectsin thisgenecan lead to Peutz-Jeghers
syndro me.
Pigmented spotson their lipsand mouths, polypsin
theurinary and gastrointestinal tracts, and an
increased risk of many typesof cancer, including
breast cancer.

14.
Non-modifiable risk factors
Family history of breast cancer:
o Having onefirst-degreerelative(mother, sister, or
daughter) with breast cancer approximately doublesa
woman'srisk.
o Having 2 first-degreerelativesincreasesher risk
about 3-fold.
o Women with afamily history of breast cancer in a
father or brother havean increased risk of BC.
o Over 85% of women with BC do no t haveafamily
history of disease.

15.
Personal history of breast cancer:
• A woman with cancer in onebreast hasa3- to
4-fold increased risk of developing anew
cancer in theother breast or in another part of
thesamebreast.
Non-modifiable risk factors

16.
Race and ethnicity
o Whitewomen areslightly morelikely to develop
breast cancer than areAfrican-American women, but
African-American women aremorelikely to dieof
thiscancer.
o However, in women < 45 yearsof age, breast cancer
ismorecommon in African- American women.
o Asian, Hispanic, and Native-American women havea
lower risk of developing and dying from breast
cancer.
Non-modifiable risk factors

17.
Dense breast tissue
o Women with denser breast tissue
(mammogram) havemoreglandular tissueand
lessfatty tissue, and haveahigher risk of
breast cancer.
o Unfortunately, densebreast tissuecan also
makeit harder to spot problemson
mammograms.
Non-modifiable risk factors

18.
Certain benign breast conditions
• Women diagnosed with certain benign breast
conditionsmay havean increased risk of
breast cancer.
Non-modifiable risk factors

19.
Proliferative lesions without atypia:
Theseconditionsshow excessivegrowth of cellsin
theductsor lobulesof thebreast tissue.
They seem to raiseawoman'srisk of breast cancer
slightly (1½ to 2 timesnormal).
They include:
• Usual ductal hyperplasia(without atypia)
• Complex fibroadenoma
• Sclerosing adenosis
• Several papillomas(called papillomatosis)
• Radial scar
Benign breast conditions

20.
Proliferative lesions with atypia:
They haveastronger effect on breast cancer risk,
raising it 4 to 5 timeshigher than normal.
Thesetypesof lesionsinclude:
• Atypical ductal hyperplasia(ADH)
• Atypical lobular hyperplasia(ALH)
Women with afamily history of breast cancer and
either hyperplasiaor atypical hyperplasiahavean
even higher risk of developing abreast cancer.
Benign breast conditions

21.
Lobularcarcinoma in situ
• In lobular carcinomain situ (LCIS) (also
called lo bular neo plasia) issometimes
grouped with ductal carcinomain situ (DCIS)
asanon-invasivebreast cancer, but it differs
from DCISin that it doesn’t seem to become
an invasivecancer if it isn’t treated.
• Women with thiscondition havea7- to 11-
fold increased risk of developing invasive
cancer in either breast.
Benign breast conditions

22.
Menstrual periods
o Early menarche(beforeage12) and/or late
menopause(after age55) haveaslightly
higher risk of breast cancer.
o Theincreasein risk may bedueto alonger
lifetimeexposureto thehormonesestrogen
and progesterone.
Non-modifiable risk factors

23.
Previous chest radiation
• Radiation therapy to thechest areaastreatment for
another cancer (such asHodgkin diseaseor non-
Hodgkin lymphoma) haveasignificantly increased
risk for breast cancer.
• Therisk of developing breast cancer from chest
radiation ishighest if theradiation wasgiven during
adolescence, when thebreastswerestill developing.
• Radiation treatment after age40 doesnot seem to
increasebreast cancer risk.
Modifiable risk factors

24.
Having children
o Women who havehad no children or who had
their first child after age30 haveaslightly
higher breast cancer risk.
o Having many pregnanciesand becoming
pregnant at ayoung agereducebreast cancer
risk.
o Pregnancy reducesawoman'stotal number of
lifetimemenstrual cycles, which may bethe
reason for thiseffect.
Modifiable risk factors

25.
Recent oral contraceptive use
o Women using oral contraceptiveshavea
slightly greater risk of breast cancer than
women who havenever used them.
o Women who stopped using oral contraceptives
morethan 10 yearsago do not appear to have
any increased breast cancer risk.
Modifiable risk factors

26.
Hormone therapy aftermenopause
• Hormonetherapy with estrogen (often with progesterone) has
been used for many yearsto help relievesymptomsof
menopauseand to prevent osteoporosis.
Thereare2 main typesof hormonetherapy.
- For women who still haveauterus, both estrogen and
progesterone(known as co mbined ho rmo ne therapy or HT).
Progesteroneisneeded becauseestrogen alonecan increasethe
risk of cancer of theuterus.
- For women with hysterectomy, estrogen alonecan be
prescribed.
Modifiable risk factors

27.
Combined hormonetherapy
o Using combined hormonetherapy after
menopauseincreasestherisk of breast cancer.
It may also increasethechancesof dying from
breast cancer.
o Thisincreasein risk can beseen with aslittle
as2 yearsof use. Combined HT also increases
thelikelihood that thecancer may befound at
amoreadvanced stage.
o A woman'sbreast cancer risk seemsto return
to that of thegeneral population within 5 years
of stopping combined treatment.

28.
Modifiable risk factors
Breast-feeding
• Breast-feeding may slightly lower breast
cancer risk, especially if breast-feeding is
continued for 1½ to 2 years.
• Theexplanation for thispossibleeffect may be
that breast-feeding reducesawoman'stotal
number of lifetimemenstrual cycles.

29.
Alcohol
o Theuseof alcohol isclearly linked to an increased
risk of developing breast cancer.
o Therisk increaseswith theamount of alcohol
consumed. Compared with non-drinkers, women who
consume1 alcoholic drink aday haveavery small
increasein risk.
o Thosewho have2 to 5 drinksdaily haveabout 1½
timestherisk of women who drink no alcohol.
Modifiable risk factors

30.
Being overweight orobese
o Being overweight or obesehasbeen found to increasebreast
cancer risk, especially for women after menopause.
o Having morefat tissueafter menopausecan increasethe
chanceof getting breast cancer by raising estrogen levels.
o Overweight tend to havehigher blood insulin levels.
o Higher insulin levelshavealso been linked to somecancers,
including breast cancer.
o Therisk appearsto beincreased for women who gained
weight asan adult but may not beincreased among thosewho
havebeen overweight sincechildhood.
o Excessfat in thewaist areamay affect risk morethan thesame
amount of fat in thehipsand thighs.
Modifiable risk factors

31.
Physical inactivity
o Evidenceisgrowing that physical activity in
theform of exercisereducesbreast cancer risk.
o In onestudy from theWomen'sHealth
Initiative(WHI) aslittleas1.25 to 2.5 hours
per week of brisk walking reduced awoman's
risk by 18%.
o Walking 10 hoursaweek reduced therisk a
littlemore.
Modifiable risk factors

32.
Factors with uncertain, controversial, orunproven effect on breast cancerrisk
Diet and vitamin intake
o Studieshavelooked at theamount of fat in thediet,
intakeof fruitsand vegetables, and intakeof meat. No
clear link to breast cancer risk wasfound.
o No study hasshown that taking vitaminsreduces
breast cancer risk.
o Most studieshavefound that breast cancer isless
common in countrieswherethetypical diet islow in
total fat, low in polyunsaturated fat, and low in
saturated fat.
o It isclear that caloriesdo count, and fat isamajor
sourceof these. High-fat dietscan lead to being
overweight or obese, which isabreast cancer risk
factor.

33.
Antiperspirants
o Rumorshavesuggested that chemicalsin underarm
antiperspirantsareabsorbed through theskin, interferewith
lymph circulation, causetoxinsto build up in thebreast, and
eventually lead to breast cancer.
o Thereisvery littleevidenceto support thisrumor.
o Onesmall study hasfound tracelevelsof parabens(used as
preservativesin antiperspirantsand other products), which
haveweak estrogen-likeproperties, in asmall sampleof breast
cancer tumors.
o But thisstudy did not look at whether parabenscaused the
tumors.
Factors with uncertain, controversial, orunproven effect on breast cancerrisk

34.
Bras
o Internet e-mail rumorsand at least onebook
havesuggested that brascausebreast cancer
by obstructing lymph flow.
o Thereisno good scientific or clinical basisfor
thisclaim.
Factors with uncertain, controversial, orunproven effect on breast cancerrisk

35.
Induced abortion
• Several studieshaveprovided very strong data
that neither induced abortionsnor spontaneous
abortions(miscarriages) havean overall effect
on therisk of breast cancer
Factors with uncertain, controversial, orunproven effect on breast cancerrisk

36.
Breast implants
o Several studieshavefound that breast implants
do not increasebreast cancer risk, although
siliconebreast implantscan causescar tissueto
form in thebreast.
o Implantsmakeit harder to seebreast tissueon
standard mammograms, but additional x-ray
picturescalled implant displacement viewscan
beused to examinethebreast tissuemore
completely.
Factors with uncertain, controversial, orunproven effect on breast cancerrisk

37.
Chemicals in the environment
o Of special interest arecompoundsin theenvironment
that found to haveestrogen-likeproperties.
o Thesecould in theory affect breast cancer risk. For
example, substancesfound in someplastics, certain
cosmeticsand personal careproducts, pesticides
(such asDDE), and PCBs(polychlorinated
biphenyls) seem to havesuch properties.
o Research doesnot show aclear link between breast
cancer risk and exposureto thesesubstances.
Factors with uncertain, controversial, orunproven effect on breast cancerrisk

38.
Tobacco smoke
o For along time, studiesfound no link between
cigarettesmoking and breast cancer.
o In recent yearsthough, somestudieshave
found that smoking may increasetherisk of
breast cancer. Theincreased risk seemsto
affect certain groups, such aswomen who
started smoking when they wereyoung.
Factors with uncertain, controversial, orunproven effect on breast cancerrisk

39.
Night work
o Several studieshavesuggested that women
who work at night — for example, nurseson a
night shift — may havean increased risk of
developing breast cancer.
o Someresearchersthink theeffect may bedue
to changesin levelsof melatonin, ahormone
whoseproduction isaffected by thebody's
exposureto light, but other hormonesarealso
being studied.
Factors with uncertain, controversial, orunproven effect on breast cancerrisk

40.
Thank you