epidemiologi ca mammae

7/17/2019 epidemiologi ca mammae

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Breast cancer—epidemiology, risk factors, and genetics

With 1 million new cases in the world each year, breast cancer is the commonest malignancy in

women and comprises 18% of all female cancers. In the United Kingdom, where the age

standardised incidence and mortality is the highest in the world, the incidence among women

aged 50 approaches two per 1000 women per year, and the disease is the single commonest case

of death among women aged !0"50, acconting for abot a fifth of all deaths in this age grop.

#here are more than 1! 000 deaths each year, and the incidence is increasing particlarly among

women aged 50"$!, probably becase of breast screening in this age grop.

Worldwide incidence of cancers in women (1980)

Site of cancer No of cases (1000s) % of total

reast 5&' 18

(er)i* !$$ 15

(olon and rectm '8$ +

tomach '$1 8

-ndometrim 1!+ 5

ng 1!& 5

/)ary 18 !



oth and pharyn* 1'1 !

/esophags 108 !

ymphoma +8

/f e)ery 1000 women aged 50, two will recently ha)e had breast cancer diagnosed and abot 15

will ha)e had a diagnosis made before the age of 50, gi)ing a pre)alence of breast cancer of

nearly '%.

Risk factors for breast cancer

ge

#he incidence of breast cancer increases with age, dobling abot e)ery 10 years ntil the

menopase, when the rate of increase slows dramatically. (ompared with lng cancer, theincidence of breast cancer is higher at yonger ages. In some contries there is a flattening of the

age"incidence cr)e after the menopase.

!eograp"ical #ariation

2ge ad3sted incidence and mortality for breast cancer )aries by p to a factor of fi)e between

contries. #he difference between 4ar -astern and Western contries is diminishing bt is still

abot fi)efold. tdies of migrants from apan to 6awaii show that the rates of breast cancer in

migrants assme the rate in the host contry within one or two generations, indicating that

en)ironmental factors are of greater importance than genetic factors.

ge at menarc"e and menopa$se

Women who start menstrating early in life or who ha)e a late menopase ha)e an increased ris7

of de)eloping breast cancer. Women who ha)e a natral menopase after the age of 55 are twice

as li7ely to de)elop breast cancer as women who e*perience the menopase before the age of !5.



2t one e*treme, women who ndergo bilateral oophorectomy before the age of 5 ha)e only

!0% of the ris7 of breast cancer of women who ha)e a natral menopase.

%stablis"ed and probable risk factors for breast cancer

Factor Relative risk High risk group

2ge 10 -lderly

9eographical location 5 :e)eloped contry

2ge at menarche enarche before age 11

2ge at menopase ' enopase after age 5!

2ge at first fll pregnancy 4irst child in early !0s

4amily history ⩾' reast cancer in first degree relati)e when yong

;re)ios benign disease !"5 2typical hyperplasia

(ancer in other breast !

ocioeconomic grop ' 9rops I and II



:iet 1.5 6igh inta7e of satrated fat

ody weight<

;remenopasal 0.& ody mass inde* 5

;ostmenopasal ' ody mass inde* 5

2lcohol consmption 1. -*cessi)e inta7e

-*posre to ionising radiation 2bnormal e*posre in yong females after age 10

#a7ing e*ogenos hormones<

/ral contracepti)es 1.'! (rrent se

6ormone replacement therapy 1.5 Use for ⩾10 years

:iethylstilbestrol ' Use dring pregnancy

ge at first pregnancy



=lliparity and late age at first birth both increase the lifetime incidence of breast cancer. #he

ris7 of breast cancer in women who ha)e their first child after the age of 0 is abot twice that of

women who ha)e their first child before the age of '0. #he highest ris7 grop are those who ha)e

a first child after the age of 5> these women appear to be at e)en higher ris7 than nlliparos

women. 2n early age at birth of a second child frther redces the ris7 of breast cancer.&amilial breast cancer—criteria for identifying women at s$bstantial increased risk

'"e following categories identify women w"o "a#e t"ree or more times t"e

pop$lation risk of de#eloping breast cancer

• 2 woman who has<

• /ne first degree relati)e with bilateral breast cancer or breast and o)arian cancer or

•

/ne first degree relati)e with breast cancer diagnosed nder the age of !0 years or onefirst degree male relati)e with breast cancer diagnosed at any age or

• #wo first or second degree relati)es with breast cancer diagnosed nder the age of $0

years or o)arian cancer at any age on the same side of the family or

• #hree first or second relati)es with breast and o)arian cancer on the same side of the

family

• 4irst degree relati)e is mother, sister, or daghter. econd degree female relati)e is

grandmother, granddaghter, ant, or niece

• Criteria for identifying o!en at very high risk in ho! gene testing !ight "e

appropriate

• 4amilies with for or more relati)es affected with either breast or o)arian cancer in three

generations and one ali)e affected relati)e

&amily "istory

Up to 10% of breast cancer in Western contries is de to genetic predisposition. reast cancerssceptibility is generally inherited as an atosomal dominant with limited penetrance.

#his means that it can be transmitted throgh either se* and that some family members may

transmit the abnormal gene withot de)eloping cancer themsel)es. It is not yet 7nown how many

breast cancer genes there may be. #wo breast cancer genes, ?(21 and ?(2', which are

located on the long arms of chromosomes 1& and 1 respecti)ely, ha)e been identified and

accont for a sbstantial proportion of )ery high ris7 families@ie those with for or more breast



cancers among close relati)es. oth genes are )ery large and mtations can occr at almost any

position, so that moleclar screening to detect mtation for the first time in an affected indi)idal

or family is technically demanding. (ertain mtations occr at high freAency in defined

poplations. 4or instance, some '% of 2sh7enaBi ewish women carry either ?(21 185 del

29 Cdeletion of two base pairs in position 185D, ?(21 58' ins ( Cinsertion of an e*tra base pair at position 58'D or ?(2 $1&! del # Cdeletion of a single base pair at position $1&!D, while

?(2' +++ del 5 Cdeletion of fi)e base pairs at position +++D acconts for abot half of all

familial breast cancer in Iceland. Inherited mtations in two other genes, p5 and ;#-=, are

associated with familial syndromes Ci"4rameni and (owdenEs respecti)elyD that inclde a high

ris7 of breast cancer bt both are rare. #hese are almost certainly other Cas yet nidentifiedD

genes that increase the ris7 of disease by only a moderate degree@perhaps three or for"fold

abo)e the general poplation le)el. #hese are nli7ely to generate florid mlti"case families bt

they are probably rather common and therefore accont for a sbstantial part of the o)erall

genetic contribtion to breast cancer.

any families affected by breast cancer show an e*cess of o)arian, colon, prostatic, and other

cancers attribtable to the same inherited mtation. ;atients with bilateral breast cancer, those

who de)elop a combination of breast cancer and another epithelial cancer, and women who get

the disease at an early age are most li7ely to be carrying a genetic mtation that has predisposed

them to de)eloping breast cancer. ost breast cancers that are de to a genetic mtation occr

before the age of $5, and a woman with a strong family history of breast cancer of early onset

who is still naffected at $5 has probably not inherited the genetic mtation.

2 womanEs ris7 of breast cancer is two or more times greater if she has a first degree relati)e

Cmother, sister, or daghterD who de)eloped the disease before the age of 50, and the yonger the

relati)e when she de)eloped breast cancer the greater the ris7. 4or e*ample, a woman whose

sister de)eloped breast cancer aged 0"+ has a cmlati)e ris7 of 10% of de)eloping the disease

herself by age $5, bt that ris7 is only 5% Cclose to the poplation ris7D if the sister was aged 50"

5! at diagnosis. #he ris7 increases by between for and si* times if two first degree relati)es

de)elop the disease. 4or e*ample, a woman with two affected relati)es, one who was aged nder

50 at diagnosis, has a '5% chance of de)eloping breast cancer by the age of $5.

re#io$s benign breast disease

Women with se)ere atypical epithelial hyperplasia ha)e a for to fi)e times higher ris7 ofde)eloping breast cancer than women who do not ha)e any proliferati)e changes in their breast.

Women with this change and a family history of breast cancer Cfirst degree relati)eD ha)e a

ninefold increase in ris7. Women with palpable cysts, comple* fibroadenomas, dct papillomas,

sclerosis adenosis, and moderate or florid epithelial hyperplasia ha)e a slightly higher ris7 of

breast cancer C1.5" timesD than women withot these changes, bt this increase is not clinically

important.



Radiation

2 dobling of ris7 of breast cancer was obser)ed among teenage girls e*posed to radiation

dring the econd World War. Ionising radiation also increases ris7 later in life, particlarly

when e*posre is dring rapid breast formation. ammographic screening is associated with a

net decrease in mortality from breast cancer among women aged o)er 50.

ifestyle

*iet

2lthogh there is a close correlation between the incidence of breast cancer and dietary fat inta7e

in poplations, the tre relation between fat inta7e and breast cancer does not appear to be

particlarly strong or consistent.

Weig"t

/besity is associated with a twofold increase in the ris7 of breast cancer in postmenopasalwomen whereas among premenopasal women it is associated with a redced incidence.

lco"ol intake

ome stdies ha)e shown a lin7 between alcohol consmption and incidence of breast cancer,

bt the relation is inconsistent and the association may be with other dietary factors rather than

alcohol.

+moking

mo7ing is of no importance in the aetiology of breast cancer.

ral contracepti#e

While women are ta7ing oral contracepti)es and for 10 years after stopping these agents, there is

a small increase in the relati)e ris7 of de)eloping breast cancer. #here is no significantly

increased ris7 of ha)ing breast cancer diagnosed 10 or more years following cessation of the oral

contracepti)e agent. (ancers diagnosed in women ta7ing the oral contracepti)e are less li7ely to

be ad)anced clinically than those diagnosed in women who ha)e ne)er sed these agents,

relati)e ris7 0.88 C0.81"0.+5D. :ration of se, age at first se, dose and type of hormone within

the contracepti)es appear to ha)e no significant effect on breast cancer ris7. Women who begin

se before the age of '0 appear to ha)e a higher relati)e ris7 than women who begin oral

contracepti)e se at an older age. #his higher relati)e ris7 applies at an age when the incidence

of breast cancer is howe)er )ery low.

Relati#e risk of breast cancer in relation to $se of oral contracepti#es



Relative risk #$% C

10 years after stopping 1

(rrent ser 1.'! 0.+$"1.05

1"5 years since stopping 1.1$ 1.08"1.'

5"+ years since stopping 1.0& 1.0'"1.1

-ormone replacement t"erapy

2mong crrent sers of 6?# and those who ha)e ceased se 1"! years pre)iosly the relati)e

ris7 of ha)ing breast cancer diagnosed increases by a factor of 1.0' C1.011"1.0$D for each year

of se. #his increase is consistent with the effect of a delay in the menopase, becase the

relati)e ris7 of breast cancer increases in ne)er sers by a factor of 1.0'8 C1.0'1"1.0!D for eachyear older at the menopase. #he ris7 of breast cancer appears higher with combined oestrogen

and progestogen combinations. 6?# increases breast density and redces the sensiti)ity and

specificity of breast screening. (ancers diagnosed in women ta7ing 6?# tend to be less

ad)anced clinically than those diagnosed in women who ha)e not sed 6?#. (rrent e)idence

sggests that 6?# does not increase breast cancer mortality.

Go to:

re#ention of breast cancer

creening as crrently practised can redce mortality bt not incidence, and then only in a

particlar age grop. 2d)ances in treatment ha)e prodced significant bt modest sr)i)al

benefits. 2 better appreciation of factors important in the aetiology of breast cancer wold raise

the possibility of disease pre)ention.

Relations"ip of -R' to breast cancer de#elopment

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1118507/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1118507/



&i!e on

HR&

'reast cancers over the 0 years

fro! age $0*0

+,tra "reast cancers in

HR& users

ndividual risk of o!en

over 0 years

=e)er !5 per 1000 @ 1 in ''

5 years se !& per 1000 ' per 1000 1 in '1

10 years se 51 per 1000 $ per 1000 1 in 1+

15 years se 5& per 1000 1' per 1000 1 in 1&"18

-ormonal control

/ne promising a)ene for primary pre)ention is inflencing the hormonal milie of women at

ris7. :ring trials of tamo*ifen as an ad3)ant treatment for breast cancer, the nmber of

contralateral breast cancers was less than e*pected, sggesting that this drg might ha)e a role in

pre)enting breast cancer. tdies comparing tamo*ifen with placebo in women at high ris7 of

breast cancer ha)e been reported and show conflicting reslts. #he =2; stdy randomised

8 women with a ris7 eAal to that of a $0 year old woman and showed a !&% redction in the

ris7 of in)asi)e breast cancer and a 50% redction in the rate of non"in)asi)e breast cancer in

women ta7ing tamo*ifen. enefits of tamo*ifen were obser)ed in all age grops. #he effect

fond for tamo*ifen also redced the o)erall incidence of osteoporotic fractres of the hip, spine

and radis by 1+%. It increased the relati)e ris7 of endometrial cancer by '.5 bt this ris7 was

limited to women aged 50 or older. ore women o)er 50 in the tamo*ifen grop de)eloped deep

)enos thrombosis, plmonary emboli and stro7e. 2n Italian stdy and a UK stdy ha)e failed toconfirm the benefits of tamo*ifen bt o)erall e)idence sggests there is a benefit of tamo*ifen in

pre)enting breast cancer. #he ongoing UK trial shold demonstrate whether this translates into a

redction in deaths from breast cancer. ?alo*ifene, a tamo*ifen"li7e compond, has been

e)alated in a poplation of 10 55 postmenopasal women being treated for osteoporosis and

has demonstrated a 5!% decrease in the nmber of breast cancers in the ralo*ifene grop. oth



the tamo*ifen and ralo*ifene stdies show a selecti)e redction in the incidence of oestrogen

receptor positi)e breast cancers.

*ietary inter#ention

If specific dietary factors are fond to be associated with an increased ris7 of breast cancerdietary inter)ention will be possible. 6owe)er, redction of dietary inta7e of sch a factor in

whole commnities may well be difficlt to achie)e withot ma3or social and cltral changes.

Weight gain by more than 10"'0 7g from the weight at age 18 does seem to be associated with an

increased ris7.

t"er pre#enti#e agents

?etinoids affect the growth and differentiation of epithelial cells, and e*periments sggest that

they may ha)e a role in pre)enting breast cancer. 2 clinical trial of fenretinoid has been reported.

In a stdy of '+&' women with breast cancer randomly allocated to fenretinoid or no treatment,no significant difference was seen in contralateral breast cancer between the two grops. #here

was a significant interaction with treatment and menopasal stats with a beneficial effect being

seen in premenopasal patients Cad3sted haBard ratio 0.$$, +5% (I 0.1!"1.0&D and an opposite

trend on postmenopasal women. elenim is another possible cancer pre)enting agent.



Worldwide data (paling baru)

There were an estimated 14.1 million cancer cases around the world in 2012,of these .4 million cases were in men and !. million in women. This

number is e"pected to increase to 24 million b# 20$%.

This growing cancer burden, within the o&erall conte"t of non'communicable

diseases (*s), was a +e# focus of the eptember 2011 - igh /e&el

eeting on *s.

oth se"es

• /ung cancer was the most common cancer worldwide contributing 1$ of the

total number of new cases diagnosed in 2012.

• reast cancer (women onl#) was the second most common cancer with

nearl# 1. million new cases in 2012.

• olorectal cancer was the third most common cancer with nearl# 1.4 million

new cases in 2012.

Rank CancerNew cases diagnosed in

2012 (1,000s)

Per cent of all cancers

(excl. non-melanoma ski

cancer)

1 /ung 1,32% 1$.0

2 reast 1,! 11.

$ olorectum 1,$!1 .

4 5rostate 1,112 .

% tomach %2 !.3




2012 (1,000s)



cancer)

! /i&er 32 %.!

er&i" uteri %23 $.

3 6esophagus 4%! $.2

ladder 4$0 $.1

10 on'odg+in

l#mphoma

$3! 2.

11 /eu+aemia $%2 2.%

12 5ancreas $$3 2.4

12 7idne# $$3 2.4

14 orpus uteri

(endometrium)

$20 2.$

1% /ip, oral ca&it# $00 2.1

1! Th#roid 23 2.1

1 rain, ner&ous s#stem 2%! 1.3

13 6&ar# 2$ 1.

1 elanoma of s+in 2$2 1.!




2012 (1,000s)



cancer)

20 8allbladder 13 1.$

21 /ar#n" 1% 1.1

22 6ther phar#n" 142 1.0

2$ ultiple m#eloma 114 0.3

24 asophar#n" 3 0.!

2% odg+in l#mphoma !! 0.%

2! Testis %% 0.4

2 7aposi sarcoma 44 0.$

epidemiologi ca mammae

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