breast cancer treatment choices

7/23/2019 breast cancer treatment choices

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THE CHOICES FORTHE CHOICES FORBREAST CANCERBREAST CANCER

TREATMENTTREATMENTNadia Califaretti MDNadia Califaretti MD

FRCPCFRCPCMedical OncologistMedical Oncologist

GRRCCGRRCC


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No con icts ofNo con icts of

interestinterest


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GoalGoal

To re ie! c"rrent infor#ation onTo re ie! c"rrent infor#ation on#a$ing an infor#ed decision#a$ing an infor#ed decisiona%o"t ad&" ant treat#ent ofa%o"t ad&" ant treat#ent of earl'earl

'stagesta

ge %reast cancer(%reast cancer(


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O%&ecti esO%&ecti esCase)%ased a**roac+ to e al"ating t+eCase)%ased a**roac+ to e al"ating t+ediagnosis and indi id"ali,ing treat#ent(diagnosis and indi id"ali,ing treat#ent(-nderstand t+e rationale for treat#ent(-nderstand t+e rationale for treat#ent(Re ie! t+e t+ree #ain treat#ent o*tions.Re ie! t+e t+ree #ain treat#ent o*tions.c+e#ot+era*'/ endocrine t+era*'/c+e#ot+era*'/ endocrine t+era*'/trast","#a%(trast","#a%(Re ie! c"rrent standard c+e#ot+era*'Re ie! c"rrent standard c+e#ot+era*'*rotocols(*rotocols(Inter*ret s"r i al data(Inter*ret s"r i al data(Inter*ret #or%idit' data(Inter*ret #or%idit' data(To re ie! +ealt+ iss"es after cancer treat#ent(To re ie! +ealt+ iss"es after cancer treat#ent(


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Mortalit' Rates in PatientsMortalit' Rates in Patients 0it+ Breast Cancer Aged 0it+ Breast Cancer Aged

12 to 34 5ears12 to 34 5ears

0

Year

105

90

75

60

45

30

15

1950 1960 1970 1980 1990 2000

A

n n u a

l d e a

t h r a

t e

p e r

1 0 0

, 0 0 0 w o m e n

UK

USA

Reprinted with permission from Elsevier Science. Lancet 2000.


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Earl' Stage BreastEarl' Stage Breast

Cancer Cancer Man' !o#en are c"red !it+ s"rger'Man' !o#en are c"red !it+ s"rger'alonealoneSo#e !o#en !ill +a e a s'ste#icSo#e !o#en !ill +a e a s'ste#icrela*serela*se

All s'ste#ic rela*ses lead to deat+ All s'ste#ic rela*ses lead to deat+Medical oncologist6s role is to assess t+eMedical oncologist6s role is to assess t+eris$ of rela*se7deat+ for an indi id"alris$ of rela*se7deat+ for an indi id"al

!o#an and #a$e reco##endations on !o#an and #a$e reco##endations on+o! to red"ce t+is ris$ +o! to red"ce t+is ris$


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Earl' Breast CancerEarl' Breast CancerTreat#ent Sc+e#aTreat#ent Sc+e#a

S-RGER5

Ad&" ant

+e#ot+era*'

Ad&" antRadiation

;7) Endocrine T<

Ad&" ant

Trast","#a%


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Case No( =Case No( =

>1)'ear)old fe#ale *atient/ +ealt+' and>1)'ear)old fe#ale *atient/ +ealt+' and*reMP*reMPR %reast l"#*ecto#'/ S?NB andR %reast l"#*ecto#'/ S?NB and

a


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Case No( = )Case No( = )C+e#ot+era*' C+e#ot+era*'

0+at is +er rec"rrence ris$ o er =2 0+at is +er rec"rrence ris$ o er =2 'ears 'ears

0it+o"t an' f"rt+er treat#ent 0it+o"t an' f"rt+er treat#ent 0it+ c+e#ot+era*' 0it+ c+e#ot+era*'

0+at is +er ris$ of d'ing fro# 0+at is +er ris$ of d'ing fro#%reast cancer !it+in =2 'ears%reast cancer !it+in =2 'ears

0it+o"t an' f"rt+er treat#ent 0it+o"t an' f"rt+er treat#ent 0it+ c+e#ot+era*' 0it+ c+e#ot+era*'


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C+e#ot+era*' for PreMPC+e#ot+era*' for PreMPBCBC

First generation *rotocolsFirst generation *rotocols .. AC < > AC < >

Second generationSecond generation*rotocols*rotocols .. AC)Ta


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Citron/ M( ?( et al( Clin Oncol @=.=> =)=> 4 @22

A Disease)free s"r i al %'dose densit'

> 'r DFS @ s 1

B O erall s"r i al %' dosedensit'

Se ere ne"tro*enia lessfreJ"ent on DD regi#en !it+

Klgrasti#(

CA?GB 4 >= Trial. Dose Dense s Standard DAC)Ta


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MA(@= Rela*se)Free S"r i al.MA(@= Rela*se)Free S"r i al. All Patients All Patients

P 0!001 "#trat$%$ed&

'()'()

('*+('*+A'*+A'*+

'()(' +

A' +

70170170

2

451441405

125101

113

2 -r 4 -r


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MA(@= Res"lts. RFSMA(@= Res"lts. RFS

LL Ad&"sted for StratiKcation Ad&"sted for StratiKcation

Treat#entTreat#ent 'ear RFS 'ear RFS LL

CEFCEF 42(= 42(=

ECEC 7T7T 4(1 4(1

AC7 AC7 TT 1(2 1(2


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Case No( =. Rec"rrence Ris$Case No( =. Rec"rrence Ris$=2 'r=2 'r

BeneKt fro# C+e#ot+era*' BeneKt fro# C+e#ot+era*'

57!6.

29!6.

P e r c e n t a g e o

f * a t i e n t s

G B H

None GG= G@

N ((


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ase No( .ase o( .S"r i al BeneKt fro#S"r i al BeneKt fro#

C+e#ot+era*' C+e#ot+era*'

Ali e in =2 'earsAli e in =2 'ears

65!2.

82!4.

P e r c e n t a g e o

f * a t i e n t s

G B H

None G= G@ G


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Case No( = EndocrineCase No( = EndocrineT+era*' T+era*'

After +er After +er rdrd c'cle of CEF/ t+e *atientc'cle of CEF/ t+e *atientsto*s +a ing #enstr"al *eriods(sto*s +a ing #enstr"al *eriods(-*on co#*letion of CEF/ s+e is-*on co#*letion of CEF/ s+e iso8ered Ta#o


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MA(1 Incidence Of CRAMA(1 Incidence Of CRAER;ER;

SI MOSSI MOS CEFCEF CMFCMF44 3@3@ @@

>2)>>>2)>> @@ 33

>1>1 @@

T0E?QE MOST0E?QE MOS

44 >> 33>2)>>>2)>> 22 33

>1>1 44 4242


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EBCTCG #eta)anal'sisEBCTCG #eta)anal'sis ))

Ta#o relati e red"ction in rec"rrencerelati e red"ction in rec"rrenceris$ at =2'ris$ at =2'

@3@3 relati e red"ction in #ortalit'relati e red"ction in #ortalit'ris$ ris$

>> red"ction in contralateral ca ris$ red"ction in contralateral ca ris$


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Ta#o


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Aro#atase In+i%itors Aro#atase In+i%itors

selecti el' %loc$ *eri*+eralselecti el' %loc$ *eri*+eralcon ersion of androstenedione tocon ersion of androstenedione toestroneestroneocc"rs in o ar'/ adi*ose tiss"e/ s$in/occ"rs in o ar'/ adi*ose tiss"e/ s$in/#"scle/ li er/ cancer cell#"scle/ li er/ cancer cellnet res"lt. in+i%ition of circ"latingnet res"lt. in+i%ition of circ"latingestradiol in ser"#estradiol in ser"# in PM !o#en onl' in PM !o#en on l' eg.eg. anastro,ole Ari#ide< / letro,oleanastro,ole Ari#ide< / letro,oleFe#araFe#ara nonsteroidal nonsteroidaleg(eg( E


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(#tro:en$o#-nthe#$#

'an er ell

u leu#

In+i%ition of In+i%ition of Estrogen)De*endent Gro!t+Estrogen)De*endent Gro!t+

;nh$ $t$ono% :rowth

(#tro:en$o#-nthe#$#

Antiestrogens

Aro#atase

in+i%itor s


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Case No( = ) Trast","#a%Case No( = ) Trast","#a%

-*on co#*letion of-*on co#*letion ofc+e#ot+era*'/ M-GA scanc+e#ot+era*'/ M-GA scanre*orts EF 14 (re*orts EF 14 (Her cancer !as HER@ne"Her cancer !as HER@ne"o ere


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Er%B@ HER@7ne"Er%B@ HER@7ne"O ere


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Er%B Rece*tor T'rosine inaseEr%B Rece*tor T'rosine inaseS'ste#S'ste#

T+e Er%B s'ste# incl"des fo"rT+e Er%B s'ste# incl"des fo"rgro!t+ factor rece*tors and t+eirgro!t+ factor rece*tors and t+eirn"#ero"s ligandsn"#ero"s ligands

I#*ortant in +"#an gro!t+ andI#*ortant in +"#an gro!t+ andde elo*#entde elo*#ent

Acti e in *roliferating cells/ Acti e in *roliferating cells/

inacti e in J"iescent cellsinacti e in J"iescent cells

1. ol"ro , ynes E. Annu Rev Pharmacol Toxicol. 200%/%%)1&5 21 .2. armor , et al. Int Radiat Oncol !iol Phys. 200%/5')&03 &13.

3. Rowins4y E. "ori#ons in Cancer Therapies: $rom !ench to !edside. 2001/2)3 35.%. +lahovic #, Crawford . Oncologist. 2003/')531 53'.


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Er%B Rece*tor T'rosineEr%B Rece*tor T'rosineinasesinases

Fo"r rece*tors.Fo"r rece*tors.Er%B)= EGFR/Er%B)= EGFR/

HER)=HER)=Er%B)@ HER)Er%B)@ HER)@7ne"@7ne"Er%B) HER)Er%B) HER)

Er%B)> HER)>Er%B)> HER)>

(r


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Er%B)@Er%B)@ or HER)@7ne"or HER)@7ne"

Beca"se of a "niJ"eBeca"se of a "niJ"eECD confor#ation/ECD confor#ation/does not %ind todoes not %ind toligands/ %"t is *ri#edligands/ %"t is *ri#ed

to di#eri,eto di#eri,e-s"all' does not-s"all' does not+o#odi#eri,e+o#odi#eri,e

Heterodi#eri,ationHeterodi#eri,ation !it+ ot+er Er%B !it+ ot+er Er%Brece*tors is necessar'rece*tors is necessar'for acti ationfor acti ation

.ol"ro , ynes E. Annu Rev Pharmacol Toxicol. 200%/%%)1&5 21 .


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Co##on Mec+anis#s of Er%BCo##on Mec+anis#s of Er%B Acti ation in T"#ors Acti ation in T"#ors Rece*torRece*tor

O ere


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Rationale for In+i%iting Er%BRationale for In+i%iting Er%BRece*torsRece*tors

Er%B rece*tor in+i%ition #a' s"**ressEr%B rece*tor in+i%ition #a' s"**resscell gro!t+/ en+ance cell deat+/ andcell gro!t+/ en+ance cell deat+/ andi#*ro e res*onse to ot+er canceri#*ro e res*onse to ot+er cancert+era*' in so#e t"#orst+era*' in so#e t"#ors

In+i%iting Er%B rece*tors #a' #oreIn+i%iting Er%B rece*tors #a' #oreselecti el' target cancer cells and s*areselecti el' target cancer cells and s*arenor#al cells/ t+ere%' red"cing "n!antednor#al cells/ t+ere%' red"cing "n!antedside e8ects of t+era*' side e8ects of t+era*'

1. Basel7a . Oncologist. 2002/ 8S$ppl %9)2 '.2. icholson R, et al. %ur Cancer. 2001a/3 8S$ppl %9)S&S15.3. icholson R, et al. %ndocr Relat Cancer . 2001"/')1 5

1'2.%. Rowins4y E. "ori#ons in Cancer Therapies: $rom !ench to !edside . 2001/2)335.5. ood"$rn . Pharmacol Ther . 1&&&/'2)2%1


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Monoclonal Anti%odiesMonoclonal Anti%odiesTrast","#a% is +"#ani,edTrast","#a% is +"#ani,ed

#onoclonal anti%od'#onoclonal anti%od'against EC do#ain of t+eagainst EC do#ain of t+eHER)@ *roteinHER)@ *rotein

Mec+anis# of action.Mec+anis# of action.In+i%it T acti ationIn+i%it T acti ation

Ind"ce rece*torInd"ce rece*torendoc'tosis andendoc'tosis anddegradationdegradationInd"ce i##"ne)Ind"ce i##"ne)#ediated c'toto


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Res"lts of Ad&" antRes"lts of Ad&" antTrast","#a% TrialsTrast","#a% Trials

NE M @221. HERA Trial andNE M @221. HERA Trial andNSABP B) =7NCCTG N4 = Trial.NSABP B) =7NCCTG N4 = Trial. ==

'ear of ad&" ant Herce*tin after 'ear of ad&" ant Herce*tin afterc+e#ot+era*' red"ces t+e ris$ of ac+e#ot+e ra*' red"ces t+e ris$ of a%reast cancer rec"rrence %' 12%reast cancer rec"rrence % ' 12Brief #edian follo!"* of =)@ 'earsBrief #edian follo!"* of =)@ 'earsSEs. +'*ersensiti it' !it+ KrstSEs. +'*ersensiti it' !it+ Krstinf"sioninf"sion

CHF 1CHF 1


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Case No( = Contin"esCase No( = Contin"es

After =2 treat#ents of Herce*tin/ After =2 treat#ents of Herce*tin/+er M-GA re eals EF >1+er M-GA re eals EF >1%aseline 14%aseline 14

Patient ad ised to sto* Herce*tinPatient ad ised to sto* Herce*tinE en t+o"g+ *atient isE en t+o"g+ *atient isas'#*to#atic/ referral is #ade toas'#*to#atic/ referral is #ade to

cardiologistcardiologistMedical #anage#ent and closeMedical #anage#ent and closefollo!)"* %' cardiologist(follo!)"* %' cardiologist(


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Trast","#a% AndTrast","#a% AndCardioto


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Case No( @Case No( @

13 'ear old +ealt+' *ostMP *atient13 'ear old +ealt+' *ostMP *atient?eft l"#*ecto#' and a


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Case No( @ )Case No( @ )C+e#ot+era*' C+e#ot+era*'

Pt !ants to %e aggressi ePt !ants to %e aggressi e !it+ treat#ent/ %"t is !it+ treat#ent/ %"t isfrig+tened %' t+e conce*t offrig+tened %' t+e conce*t ofc+e#ot+era*' c+e#ot+era*' Ris$ of rela*se at =2'ears isRis$ of rela*se at =2'ears is11C+e#o o*tions are re ie!edC+e#o o*tions are re ie!ed


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Case No( @ Contin"esCase No( @ Contin"esFirst generation *rotocolsFirst generation *rotocols

AC AC %eneKt%eneKt

Second generation *rotocolsSecond generation *rotocols AC)Ta


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Case No( @ EndocrineCase No( @ EndocrineT+era*' T+era*'

Baseline M-GA EF 11Baseline M-GA EF 11 AC ad#inistered J !ee$s < AC ad#inistered J !ee$s c'cles !it+o"t serio"s> c'cles !it+o"t serio"se8ectse8ects After c+e#o co#*leted s+e After c+e#o co#*leted s+e

starts ad&" ant letro,olestarts ad&" ant letro,ole@(1#g *o od for *lanned 1@(1#g *o od for *lanned 1

'ears 'ears


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Earl' -*front Ad&" antEarl' -*front Ad&" antTrialsTrials

0*5 -ear#Sur:er-

+A=(>(=

A AS+/? +A=

+A=

A AS+/?

@(+/?+A=

/

/

/

+A=@(+/?

@(+/?+A=

A+A'

+(A=


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. RateRate

in t+e Ad&" ant Settingin t+e Ad&" ant SettingFollo!)"*Follo!)"*#o#o Rel( Red(Rel( Red( A%s( Red( A%s( Red( Early Early TAM 5 vs noneTAM 5 vs none 120120 4747 12 (5 yrs)12 (5 yrs)

Earl' Earl' ANA 1 s TAM 1 ANA 1 s TAM 1 33 == ( 3 'rs( 3 'rs

Earl' Earl' ?ET 1 s( TAM 1?ET 1 s( TAM 1 @1(@1( =4=4 @(3 1 'rs@(3 1 'rs

Earl'Earl'seJ(seJ(

TAM @TAM @ E E sE E sTAM 1TAM 1 2(32(3 @@ >( 'rs>( 'rs

Earl'Earl'

seJ(seJ(

TAM @TAM @ ANA s ANA s

TAM 1TAM 1@@ >2>2 (= 'rs(= 'rs

E@ >(3 > 'rs>(3 > 'rs

(


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Relati e E8ect of AIs on Post MPRelati e E8ect of AIs on Post MPRec"rrences at 1 5earsRec"rrences at 1 5ears

rec"rrences !it+ no ad&" ant treat#entEBCTCG

> ris$ red"ction !it+ Ta#o


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ASCO Technology Assessment 2004ASCO Technology Assessment 2004

Optimal adjuvant hormonal therapy for aOptimal adjuvant hormonal therapy for aPM oman ith receptor ! cancerPM oman ith receptor ! cancer

"#C$%&'S an A" as initial therapy O("#C$%&'S an A" as initial therapy O(after treatment ith tamo)ifenafter treatment ith tamo)ifen


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Total C+olesterol in BIG =)Total C+olesterol in BIG =)

4 . S"##ar' 4 . S"##ar' Ser"# c+olesterol decreased %'Ser"# c+olesterol decreased %'

=@ in t+e ta#o


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AIs and Bone AIs and Bone

#O(MA$ *O#' OST'OPO(OT"C *O#'

+'(T'*(A$ COMP('SS"O#,(ACT%('

s eo*oros s rac "ress eo*oros s rac "res


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s eo*oros s rac ress eo*oros s rac resRe*orted in Ad&" ant AIRe*orted in Ad&" ant AI

TrialsTrials

A+A' +r$al$#t#H roup Lancet 2005B365 60B +hCrl$mann et al. www!$ #:!or:B 'oom e# et al. N Engl J Med 2004B350 1081B DaEe#F et al. Breast Cancer Res Treatm 2004B88 S7"A #tra t 2&B o## et al. N Engl J Med 2003B349 1793!

A+A'

(=

A A

+A=

+A=

)ra ture?#teoporo#$#

)ra ture

3!1 # 2!37!4 # 5!7

2!4 # 2!1

0!080!05

;

=A*17 28 @(+/? Pla e o )ra ture?#teoporo#$#

3!6 # 2!95!8 # 4!5

0!240!07

=our$d#en 0305

Stud- )U"=?& A; /e%! ru: ( ent A; # /e%!".& P

ATAC Bone Fract"re Ad erseATAC Bone Fract"re Ad erse


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ATAC. Bone Fract re Ad erse ATAC. Bone Fract re Ad erseE ents at Treat#entE ents at Treat#ent

Co#*letion Anal'sisCo#*letion Anal'sis

Anastro,ole Anastro,ole of *atients of *atients

n 24@n 24@

Ta#o

*) al"e*) al"e

oint Disorders oint Disorders 1(3 @ (1(3 @ ( @4(1@4(1@=(@@=(@ 2(222=2(222=

All Fract"res All Fract"res

)) s*ines*ine ) +i*) +i* ) !rist) !rist

==(2 1(==(2 1(

=(1=(1=(@=(@@(@(

( (( (

2(42(4=(2=(2@(2@(2

2(222=2(222=

2(22(22(12(12(>2(>

Bis*+os*+onateBis*+os*+onate"sage"sage 4(3

4(3 3(>3(> ATAC Trialists6 Gro"*( SABCS @22>( ATAC Trialists6 Gro"*( SABCS @22>( ?ancet @221 31. 32)3@(?ancet @221 31. 32)3@(


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Ho! Serio"s Is T+isHo! Serio"s Is T+isDi8erenceDi8erence

No *lace%o ar#No *lace%o ar# 0+at fract"re rate #ig+t nor#all' 0+at fract"re rate #ig+t nor#all'%e o%ser ed in a si#ilarl' aged%e o%ser ed in a si#ilarl' aged*o*"lation*o*"lation

=@)@1 U *er =222 *atient 'ears=@)@1 U *er =222 *atient 'ears ATAC Ta#. = (>> U *er =222 *t ATAC Ta#. = (>> U *er =222 *t

'ears 'ears ATAC Ari#ide


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ATAC BMD S"%st"d' ATAC BMD S"%st"d'

No %is*+os*+onates allo!edNo %is*+os*+onates allo!ed@ 'ears A > loss in ?S@ 'ears A > loss in ?S

(@ loss in +i*(@ loss in +i*

@ 'ears Ta# =(4 gain in ?S@ 'ears Ta# =(4 gain in ?S =(@ gain in +i*=(@ gain in +i*

Considered s#all losses co#*ared toConsidered s#all losses co#*ared tot+e nat"ral BMD loss t+at occ"rs int+e nat"ral BMD loss t+at occ"rs in#eno*a"se#eno*a"seBeneKts of t+e dr"g o"t!eig+ t+is ris$BeneKts of t+e dr"g o"t!eig+ t+is ris$


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Patient Reco##endationsPatient Reco##endationsOn AIsOn AIs

Sto* s#o$ingSto* s#o$ingRed"ce ca8eine and alco+ol inta$eRed"ce ca8eine and alco+ol inta$e

Perfor# reg"lar !eig+t)%earingPerfor# reg"lar !eig+t)%earinge


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Patient Reco##endationsPatient Reco##endationsOn AIsOn AIs

BMD *erfor#ed at %aseline and J=@)BMD *erfor#ed at %aseline and J=@)= #os= #os If *atient +as +ad an osteo*orotic U/ addIf *atient +as +ad an osteo*orotic U/ add

a %is*+os*+onate rig+t a!a' a %is*+os*+onate rig+t a!a' If t+ere is e idence of OP/ addIf t+ere is e idence of OP/ add%is*+os*+onate rig+t a!a' %is*+os*+onate rig+t a!a' If t+ere is osteo*enia/ e al"ate ot+erIf t+ere is osteo*enia/ e al"ate ot+er

RFs and consider %is*+os*+onateRFs and consider %is*+os*+onateIf follo!)"* BMD loss ?S or 1If follo!)"* BMD loss ?S or 1FN/ add a %is*+os*+onateFN/ add a %is*+os*+onate


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Case No( @ Contin"esCase No( @ Contin"es

> 'ears later s+e re*orts *rofo"nd> 'ears later s+e re*orts *rofo"ndfatig"e < @ #osfatig"e < @ #osDro*s in to o8ice to see +er SCC/Dro*s in to o8ice to see +er SCC/

co#*laining of fatig"e/ !ants to set "*co#*laining of fatig"e/ !ants to set "*an a**oint#ent !it+ oncologistan a**oint#ent !it+ oncologistSCC notes s+e is in ra*id AFi% andSCC notes s+e is in ra*id AFi% andsends +er to ER sends +er to ER

Cardiologist diagnoses +er !it+Cardiologist diagnoses +er !it+ant+rac'cline)ind"ced cardio#'o*at+'ant+rac'cline)ind"ced cardio#'o*at+'reJ"iring #edical #anage#entreJ"iring #edical #anage#ent


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C+e#ot+era*' RelatedC+e#ot+era*' Related Cardioto


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Cardiac To


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Concl"sionsConcl"sions

e' ad ances in t+e #anage#ent of %reast cancere' ad ances in t+e #anage#ent of %reast cancer+a e %een #ade in t+e last fe! 'ears+a e %een #ade in t+e last fe! 'ears

Ad&" ant treat#ent is indi id"ali,ed to *ossi%l' Ad&" ant treat#ent is indi id"ali,ed to *ossi%l'incl"de c+e#ot+era*'/ +or#one t+era*' andincl"de c+e#ot+era*'/ +or#one t+era*' andtrast","#a%trast","#a%

Ne! treat#ents are intensi e and #a' res"lt in long)Ne! treat#ents are intensi e and #a' res"lt in long)ter# +ealt+ concernster# +ealt+ concernsE idence)%ased/ infor#ati e disc"ssion to re ie! ris$sE idence)%ased/ infor#ati e disc"ssion to re ie! ris$sand %eneKts for eac+ *atient is of critical i#*ortanceand %eneKts for eac+ *atient is of critical i#*ortance


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T+an$ 'o" forT+an$ 'o" for

'o"r attention 'o"r attention

breast cancer treatment choices

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