breast cancer drug therapy 2004a

Breast Cancer Breast Cancer Drug Therapy 2004Drug Therapy 2004

Dr. Shad Salim AkhtarDr. Shad Salim AkhtarMBBS, MD, FRCP (Edin), FACP(USA)MBBS, MD, FRCP (Edin), FACP(USA)Member Association of UICC FellowsMember Association of UICC Fellows

Consultant Medical OncologistConsultant Medical OncologistMedical DirectorMedical DirectorPrince Faisal Oncology CenterPrince Faisal Oncology CenterKing Fahd Specialist HospitalKing Fahd Specialist HospitalBuraidah Al-Qassim, KSABuraidah Al-Qassim, KSA

Screening

Diagnosis

Surgery

Adjuvant therapy

Quality of life

Early

detection

Type o

f surg

ery

ChemotherapyRadiotherapy

ReconstructionEnd of life-care quality

Pain control

Hormone therapyPREVENTION???

Drug Therapy in Breast CancerDrug Therapy in Breast Cancer

PreventionPreventionAdjuvantAdjuvantNeoadjuvantNeoadjuvantMetastaticMetastatic

Can We Prevent It?

ChemopreventionChemopreventionAdjuvant trialsAdjuvant trials of tamoxifen confirmed of tamoxifen confirmed– Lowered odds of recurrence (47%)Lowered odds of recurrence (47%)– Lowered contralateral breast cancer (47%)Lowered contralateral breast cancer (47%)

Five major hormonal Five major hormonal prophylaxis trialsprophylaxis trials– IBIS-I (7,139)IBIS-I (7,139)– NSABP-P1 (13,388)NSABP-P1 (13,388)– UK (2,471)UK (2,471)– Italian (5,408)Italian (5,408)– MORE (7,705)MORE (7,705)Cuzick J et al. Lancet 2003; 361:296

Chemoprevention Trials CriteriaChemoprevention Trials Criteria

>2 fold relative risk>2 fold relative risk>1.6% risk according to Gail model>1.6% risk according to Gail modelHigh risk family historyHigh risk family historyNormal risk hysterectomyNormal risk hysterectomyNormal risk postmenopausalNormal risk postmenopausal

Cuzick J et al. Lancet 2003; 361:296

Hazard Ratio of Developing All Cancers Including DCIS

Royal Marsden NSABP-P1 Italian IBIS-I

Side effects noticed in the tamoxifen prevention trials

Hazard Ratio of Developing Endometrial Cancer

Hazard ratio of venous thromboembolic events

Hazard Ratio of death from any cause

ChemopreventionChemopreventionTamoxifen reduces the risk of ER + tumorsTamoxifen reduces the risk of ER + tumorsSide effects need to be reducedSide effects need to be reducedLow dose?Low dose?Added aspirin low doseAdded aspirin low doseCareful selection of candidatesCareful selection of candidatesRaloxifene may be betterRaloxifene may be betterAromatase inhibitors being investigatedAromatase inhibitors being investigatedNew drugs with low profile of side effectsNew drugs with low profile of side effects

Cuzick J et al. Lancet 2003; 361:296

ChemopreventionChemoprevention

Absolute risk reduction must be weighed Absolute risk reduction must be weighed against potential harmsagainst potential harmsFDA approvalFDA approval::– Tamoxifen may be used for breast cancer risk Tamoxifen may be used for breast cancer risk

reduction in women who are 35 years of age reduction in women who are 35 years of age or older and have a 5 year risk of at least or older and have a 5 year risk of at least 1.67%1.67%

Kinsinger L S et al. Ann Intern Med 2002; 137:59

Breast Cancer-TreatmentBreast Cancer-Treatment

Halsted hypothesisHalsted hypothesis– Local control improves survivalLocal control improves survival

Systemic hypothesisSystemic hypothesis– Local control has no impact on survivalLocal control has no impact on survival

Present UnderstandingPresent Understanding– Maximal disease controlMaximal disease control

LocoregionalLocoregionalSystemicSystemic

Adjuvant Medical TherapyAdjuvant Medical Therapy

EndocrineEndocrineChemotherapyChemotherapyOthersOthersWho shall get it?Who shall get it?How long shall it be given?How long shall it be given?What type?What type?What dose?What dose?

Areas of ConsensusAreas of Consensus

Are there predictive markers that Are there predictive markers that individualize the therapy?individualize the therapy?Who needs the treatment?Who needs the treatment?Which therapy is effective?Which therapy is effective?

Predictive Markers That We Predictive Markers That We Have?Have?

Definition of Risk Categories-St Gallen 2003Definition of Risk Categories-St Gallen 2003

Risk CategoryRisk Category Node NegativeNode Negative Node +veNode +veHR +veHR +ve HR -veHR -ve

Minimal/Minimal/LowLow

All of the followingAll of the followingpT<=2 cmspT<=2 cmsGrade 1 andGrade 1 andAge >=35 yearsAge >=35 years

Not Not applicableapplicable

Not Not applicableapplicable

Average/Average/HighHigh(? (? Vascular Vascular /Lymphatic /Lymphatic Invasion)Invasion)

At least one of the At least one of the followingfollowingpT>2 cms orpT>2 cms orGrade 2-3 orGrade 2-3 orAge <35 yearsAge <35 years

ER and ER and PgR PgR absentabsent

All high All high riskrisk

Goldhirsch A et al: Meeting highlights J Clin Oncol 2003;21:3357

Adjuvant Systemic Therapy for Patients with Adjuvant Systemic Therapy for Patients with Operable Breast Cancer-St. Gallen 2003Operable Breast Cancer-St. Gallen 2003

Node Negative HR+Node Negative HR+

Risk GroupRisk Group PremenopausalPremenopausal PostmenopausalPostmenopausal

Minimum RiskMinimum Risk Tamoxifen or noneTamoxifen or none Tamoxifen or Tamoxifen or nonenone

Average RiskAverage Risk GnRH analogue or GnRH analogue or Ovarian ablation +Ovarian ablation +Tam {Tam {++CT} orCT} orCT Tam {CT Tam {++GnRH GnRH anal (or Ov ab)} or anal (or Ov ab)} or Tam or GnRH Tam or GnRH analogue analogue

Tamoxifen orTamoxifen orCT Tam CT Tam

Goldhirsch A et al: Meeting highlights. J Clin Oncol 2003;21:3357


Node Positive HR+Node Positive HR+

PremenopausalPremenopausal PostmenopausalPostmenopausal

Chemotherapy TamChemotherapy Tam{{++GnRH anal (or Ov GnRH anal (or Ov abl)}abl)}GnRH analogue (Ov GnRH analogue (Ov abl)+abl)+Tam {Tam {++Chemotherapy}Chemotherapy}

CT Tam or CT Tam or TamoxifenTamoxifen



HR-HR-

Risk groupRisk group PremenopausalPremenopausal PostmenopausalPostmenopausal

Node negativeNode negative ChemotherapyChemotherapy ChemotherapyChemotherapy

Node positiveNode positive ChemotherapyChemotherapy ChemotherapyChemotherapy


Tamoxifen: Improvement inTamoxifen: Improvement inDisease-Free SurvivalDisease-Free Survival

Reprinted from The Lancet, vol 351, Early Breast Cancer Trialists’ Collaborative Group, 1451, 1998,with permission from Elsevier Science.

Years

100

% R

ecur

renc

e-fr

ee

90

80

60

40

20

05 10+0

Node -ve: 14.9% SD 1.4: 2P<0.00001Node +ve: 15.2% SD 2.5: 2P<0.00001

Node -ve

Node +ve

87.4

79.274.9

75.6 64.3

59.758.3

44.5

70

50

30

10

Absolute Recurrence Reduction

Tamoxifen (~5 y)Placebo

Placebo

Tamoxifen (~5 y)

Recurrence as First Event

TamoxifenTamoxifen

Should be used in all ER +ve pts regardless Should be used in all ER +ve pts regardless of:of:– AgeAge– Menopausal statusMenopausal status– Axillary node involvementAxillary node involvement– Tumor sizeTumor size

NIH and St Gallen Consensus Conferences

Tamoxifen When?Tamoxifen When?

Sequential better ?Sequential better ?Data from ECOG trialData from ECOG trial– PremenopausalPremenopausal– Node positiveNode positive– ER positiveER positive– CAF vs CAF+OA vs CAF+OA+TAMCAF vs CAF+OA vs CAF+OA+TAM– Last combination superiorLast combination superior

Davidson N et al: Proc Am Soc Oncol 1999; 18:67a (abstract 249)

2727

Estrogenbiosynthesis

Tumor cell

Nucleus

Inhibition ofEstrogen Dependent Growth

Inhibition of cell

proliferation

Estrogenbiosynthesis

Antiestrogens

Aromataseinhibitors

ATAC TrialATAC TrialAnastrozolAnastrozolee

TamoxifenTamoxifen Comb(%Comb(%))

Total(%)Total(%)

Ist Ist eventevent

31253125 31163116 31253125 93669366

LRLR 6767 8383 8181 231231DRDR 158158 182182 204204 544544Contral Contral CaCa

1414 3333 2828 7575

Deaths Deaths before Rbefore R

7878 8181 7070 229229

TotalTotal 317317((10.1%)10.1%) 379379((12.2%)12.2%) 383383((12.312.3)) 10791079((11.5)11.5)ATAC Trialists Group: Lancet 2002; 359:2131

Tamoxifen How Long?Tamoxifen How Long?

TrialTrial DesignDesign StatusStatus TargetTarget ResultResultNSABP NSABP B-14B-14

5yrs vs 5yrs vs ContdContd

ReportedReported 11721172 Equivalence for OSEquivalence for OSLong use more End CaLong use more End Ca

ECOGECOGE4181E4181

5 yrs vs 5 yrs vs ContdContd

ReportedReported Equivalence for RFSEquivalence for RFS

ScottishScottish 5 yrs vs 5 yrs vs ContdContd

ReportedReported 342342 Equivalence for RFSEquivalence for RFSLong use more End CaLong use more End Ca

ATLASATLAS 5 yrs vs 10 5 yrs vs 10 yrs in ER+yrs in ER+

OpenOpen 2000020000 N/AN/A

ATTOMATTOM 5yrs vs 10 5yrs vs 10 yrs ER +?yrs ER +?

OpenOpen ?? N/AN/A

Lohrisch C et al: Eur J Cancer 2001; 37 (s7):45

Years

8585

76766868

7373

62625454

68%54%

0

20

40

60

80

100

0 5 10 15

Breast Cancer Recurrences Breast Cancer Deaths

0

20

40

60

80

100

0 5 10 15

73%

64%

9191

8080

73738787

7373

6464

Years

Timing of Breast Cancer EventsTiming of Breast Cancer Events

Oxford Overview 2000 – adapted with permission

TamoxifenControlTamoxifen

Control

15% 17% 9% 18%

FEMARA Placebo Hazard Ratio (n=2575) (n=2582) (95% Cl) P Value

4-y DFS rate 93% 87% 0.57 (0.43 - 0.75) 0.00008

Events 75 132

MA.17 Results: MA.17 Results: Disease-Free SurvivalDisease-Free Survival

Goss et al. N Engl J Med. 2003;349:1793-1802.

• Letrozole (FEMARA) decreased the risk of recurrence by 43% versus placebo

• Median duration of follow-up was 2.4 years.

3232

MA.17 Results: Total Recurrences of Breast Cancer

26 14

30

14

76

47

0

20

40

60

80

100

120

140

Placebo Letrozole

DistantLoco-regionalNew primary only

132

75

Placebo FEMARAGoss et al. N Engl J Med. 2003;349:1793-1802.

3333

MA.17 Results: Type of Event

FEMARA Placebo

(n=2575)(n=2582)

Recurrences total 61 (2.4%) 106 (4.1%)

Local only 6 19Local chest wall 2 7Regional LN 6 4Distant* 47 76

Contralateral BC only 14 (0.5%) 26 (1.0%)

Total 75 132*Patients may have more than one site of recurrence.

Goss et al. N Engl J Med. 2003;349:1793-1802..

3434

MA.17 Results: Disease-Free Survival by Treatment Duration

80828486889092949698

100

Year 1 Year 2 Year 3 Year 4

Treatment duration

% D

isea

se-fr

ee s

urvi

val Letrozole (Femara)

Placebo


87%

93%

• Increasing benefit in estimated DFS with treatment duration

MA.17 Results: MA.17 Results: Overall SurvivalOverall Survival

FEMARA Placebo Hazard Ratio (n=2575) (n=2582) (95% Cl) P Value

4-y OS rate 96% 94% 0.76 (0.48 – 1.21) 0.25

Events 31 42


• Letrozole (FEMARA) decreased the risk of death by 24% versus placebo

• Median duration of follow-up was 2.4 years.

3636

MA.17 Results: Overall Survival

FEMARA 2575 2329 1349 641 188 9 0Placebo 2582 2328 1335 645 196 14 0

Months after randomization

Wom

en s

urvi

ving

(%)

0

20

40

100

0 10 20 30 40 50 60

60

80

Number at risk:

FEMARAPlacebo


P = 0.25

3737

FEMARA Placebo (n=2154) (n=2145) P Value

Hot flashes 47 41 <0.0001Arthralgia 21 17 <0.0001Myalgia 12 10 0.02Edema 17 16 0.17Hypercholesterolemia 12 12 0.67Cardiovascular events 4 4 0.40Fractures 3.6 2.9 0.24Osteoporosis 6 5 0.07Vaginal bleeding 4 6 0.012Med d/c due to toxicity 4.5 3.6 0.11

MA.17 Results: Safety (All Grades)

% of Patients


Coombs RC et al. N Engl J Med 2004; 350:1081

Run For Femara?Run For Femara?Early termination of trialEarly termination of trial<1% women received 4 yrs Rx<1% women received 4 yrs RxMedian follow up only 2.4yrsMedian follow up only 2.4yrsDoes reduce recurrence by 2.2%Does reduce recurrence by 2.2%No significant difference in overall survivalNo significant difference in overall survivalSide effects and may be long termSide effects and may be long termMain impact on ipsilateral and contralateral Main impact on ipsilateral and contralateral recurrencerecurrenceIf a woman wishes to use Femara let it be If a woman wishes to use Femara let it be known to her…..known to her…..Burstein HJ. N Engl J Med 2003; 349:1857

Run For ExamestaneRun For Examestane

90% patients completed the trial (5 yrs)90% patients completed the trial (5 yrs)Data is immature forData is immature for– Overall survival Overall survival – SafetySafety

Discuss the issue in detail with the patientDiscuss the issue in detail with the patient

Piccart MJ. N Engl J Med 2004; 350:1140

Who Should Receive Aromatase Who Should Receive Aromatase Inhibitors As AdjuvantInhibitors As Adjuvant

Women at high risk of recurrence

Piccart MJ. N Engl J Med 2004; 350:1140

Adjuvant Medical TherapyAdjuvant Medical TherapyOxford Overview 2000-Ovarian AblationOxford Overview 2000-Ovarian Ablation

In the absence of CT Ovarian Ablation in <50 yrs In the absence of CT Ovarian Ablation in <50 yrs of ageof age– Reduces Br Ca Rec-8.5%Reduces Br Ca Rec-8.5%– Improves survival-9.8%Improves survival-9.8%

OA + CT no such benefitOA + CT no such benefitSpecific focus on HR+ premenopausal pts not Specific focus on HR+ premenopausal pts not availableavailableMay be used as an alternative to CT in ER May be used as an alternative to CT in ER rich ptsrich pts– Definite premenopausalDefinite premenopausal– Tam must be addedTam must be added

Shall we stop using TamoxifenShall we stop using Tamoxifen

NONOSingle trialSingle trialShort follow upShort follow upSafety for 5 yrs?Safety for 5 yrs?Additive effect over years?Additive effect over years?Carry over effect?Carry over effect?

When to use Anastrozole?When to use Anastrozole?

As adjuvant in As adjuvant in – Postmenopausal ptPostmenopausal pt– HR +ve tumourHR +ve tumour

May be considered in pts with Tam May be considered in pts with Tam contraindicationcontraindicationNO IndicationNO Indication– To switch from Tam to AnastrozoleTo switch from Tam to Anastrozole– To add after 5 yrs of TamTo add after 5 yrs of Tam– Other AI equivalent?Other AI equivalent?

Risk of Recurrence Node negativeRisk of Recurrence Node negative

Risk level Rec at 10yrsLow Risk <10 %

High Risk ~20 %Intermediate Risk 10-20%

EBCTG: Lancet 1992; 339:1

10 Year Survival in Node Positive10 Year Survival in Node Positive

Risk level 10 yr surv1-3 nodes 40-60 %>=4 nodes 25%


Absolute reduction in mortalityAbsolute reduction in mortalityEffect of medical therapyEffect of medical therapy

10 yr risk of death Abs benefit in 100 women from breast cancer if therapy reduces ann (%)

odds of death by

10-20 4 220-40 8 440-80 12 6


30% <15 %

Adjuvant Medical Therapy 2000 Oxford Overview Adjuvant Medical Therapy 2000 Oxford Overview 3-6 months Chemotherapy3-6 months Chemotherapy

Pre -ve 7%Pre +ve11%Post -ve 2%Post +ve 3%

2000 Review unpublished data

Menop Node Imp in Surv

Regardless of tamoxifen usage

Chemotherapy in Premenopausal PtsChemotherapy in Premenopausal Pts

Regardless of HR statusRegardless of HR statusAll node positive patientsAll node positive patientsNode negative with non low risk statusNode negative with non low risk statusIn very low risk HR-ve otherwise good In very low risk HR-ve otherwise good prognosis role unknown, most would use itprognosis role unknown, most would use itIn very low risk node-ve disease uncertainIn very low risk node-ve disease uncertain


Chemotherapy in Postmenopausal PtsChemotherapy in Postmenopausal Pts

50-69 yrs old50-69 yrs oldIrrespective of addition of TamIrrespective of addition of TamNode Positive/Node NegativeNode Positive/Node NegativeER –ve or ER ? Greatest advantageER –ve or ER ? Greatest advantageOffering CT to ER+ pts considerOffering CT to ER+ pts consider– Pt/tumor characteristicsPt/tumor characteristics– Co morbid conditionsCo morbid conditions


Which Chemotherapy?Which Chemotherapy?

Which Chemotherapy?Which Chemotherapy?

Standard regimens consist ofStandard regimens consist of– CMF/Anthracycline based CTCMF/Anthracycline based CTAnthracyclin vs CMF Anthracyclin vs CMF – 4% absolute reduction as compared to CMF for 4% absolute reduction as compared to CMF for

death and recurrencedeath and recurrenceIn node negative setting (1.7%) ? Less In node negative setting (1.7%) ? Less benefitbenefitBoth regimens have toxicityBoth regimens have toxicity

Piccart M et al: ASCO Education Book 2002; 144

Which Chemotherapy?Which Chemotherapy?Anthracycline basedAnthracycline based– Premenopausal womenPremenopausal women

Node positiveNode positiveNode negative high riskNode negative high risk

CMFCMF– In patientsIn patients

With high risk of cardio toxicityWith high risk of cardio toxicityLow risk diseaseLow risk disease

TaxanesTaxanes– No established role yet as adjuvantNo established role yet as adjuvant

Piccart M et al: ASCO Education Book 2002; 144

Two populations of br ca-peak incid of Two populations of br ca-peak incid of recurrecur– 2 years2 years– 5 years 5 years

6 cycles important in the former6 cycles important in the formerSuperiority of Anthracycline regimen in 3 Superiority of Anthracycline regimen in 3 drug combinationsdrug combinationsIn non high risk patients 4 (F)AC or 6 CMF In non high risk patients 4 (F)AC or 6 CMF may be enoughmay be enoughIn high risk patients 6 FAC (FEC)In high risk patients 6 FAC (FEC)

Chemotherapy-Optimum Dose/Cycles?Chemotherapy-Optimum Dose/Cycles?

Chemotherapy When to Start?Chemotherapy When to Start?

IBCSG Trials reviewIBCSG Trials reviewER –ve ptsER –ve pts– Within 21 days of surgery 10 yr DFS 60%Within 21 days of surgery 10 yr DFS 60%– After 21 days 10 yr DFS 34 %After 21 days 10 yr DFS 34 %

ER positive pts no differenceER positive pts no differenceShould be instituted within 4-6 (12) wks of Should be instituted within 4-6 (12) wks of surgerysurgery

Tamoxifen+ ChemotherapyTamoxifen+ Chemotherapy

Postmenopausal womenPostmenopausal womenCT+Tam have additive effect?CT+Tam have additive effect?In ER+ pts no definite added benefit In ER+ pts no definite added benefit confirmedconfirmed– Trials are on stillTrials are on still– In high risk patients CT may be added to In high risk patients CT may be added to

hormonal agenthormonal agent

Keep in mind the benefit and toxicityKeep in mind the benefit and toxicity

Tamoxifen+ ChemotherapyTamoxifen+ Chemotherapy

Premenopausal womenPremenopausal womenTrials are on to answer this questionTrials are on to answer this questionOverview found a highly significant surv Overview found a highly significant surv benefitbenefitSide effects are lowSide effects are lowMay be given pending the results of the trialsMay be given pending the results of the trialsIn node –ve low risk Tam or noneIn node –ve low risk Tam or none

Ovarian Ablation + CT Added Benefit?Ovarian Ablation + CT Added Benefit?

IBCSG Trial VIIIIBCSG Trial VIII– Node –ve/any receptorNode –ve/any receptor– CMFx6 vs Gx18 vs CMF+GCMFx6 vs Gx18 vs CMF+G– Equivalence in ER +ve ptsEquivalence in ER +ve pts

ZIPP TrialZIPP Trial– Tam vs No TamTam vs No Tam– Z vs No ZZ vs No Z– CT vs No CTCT vs No CT– Addition of Z betterAddition of Z better– Reanalysis-no improvement in pts who had Reanalysis-no improvement in pts who had

CT+TamCT+Tam

Ovarian Ablation + CT Added Benefit?Ovarian Ablation + CT Added Benefit?

In view of the available data this cannot be recommended at this stage


Endocrine non Responsive

Chemotherapy

Endocrine Responsive

Node negative

Minimal /lowrisk

Average/high risk

OA+TamCT+TamTamOA

Tam

Nil

PostmenopTamTam+CT

Premenop

Node positive

CT+TamOA+Tam

PostmenopTamTam+CT

Premenop


Unsolved ProblemsUnsolved ProblemsElderly patients HR-veElderly patients HR-ve< 1 cms tumor size< 1 cms tumor sizeAverage/high risk node negative HR+Average/high risk node negative HR+– OA/CT/TamOA/CT/Tam

Post CT OA in premenopausal HR+ Post CT OA in premenopausal HR+ patientspatients

Lump Size

TT ItalyItaly Al-QassimAl-QassimTisTis 55 00T1T1 412412 33T2T2 444444 2525T3T3

95952323

T4T4 1717

90%

59%

Montella M et al. Cancer 1995;76:1585Akhtar SS. Int J Health Care Quality in press

Breast Cancer-Nodal StatusBreast Cancer-Nodal Status

15

33N0N111

15

7 Unk>31to3

69% node positive

Number of nodes=2-40Number positive =1-23

Akhtar SS. Proceedings ASCO 2002; 127

Neoadjuvant TherapyNeoadjuvant TherapyInoperable breast cancer Inoperable breast cancer (Standard)(Standard)– Stage Stage IIIAIIIA-IIIB or T3 T4 disease-IIIB or T3 T4 disease– Inflammatory breast carcinomaInflammatory breast carcinoma– Ipsilateral supra/infra clavicular node Ipsilateral supra/infra clavicular node

involvementinvolvement– Where local control cannot be achievedWhere local control cannot be achieved

A candidate for mastectomy wishes to have A candidate for mastectomy wishes to have BCT BCT (Alternative)(Alternative) results in large tumours results in large tumours show poor outcomeshow poor outcomeStage III A may be treated with surgery firstStage III A may be treated with surgery firstShenkeir T et al. CMAJ 2004; 170:983

Neoadjuvant TherapyNeoadjuvant TherapyCore biopsy essential for adequate Core biopsy essential for adequate pathological studypathological studyChemotherapy like FAC X 4-6 cyclesChemotherapy like FAC X 4-6 cyclesHormonal agents in patients not fit for Hormonal agents in patients not fit for chemotherapy (Receptor + only)chemotherapy (Receptor + only)Aromatase inhibitors preferred in Aromatase inhibitors preferred in postmenopausal patientspostmenopausal patientsSurgery (if operable) and Adj therapy to followSurgery (if operable) and Adj therapy to followRole of postop chemotherapy not clear yetRole of postop chemotherapy not clear yet

Kaufmann M et al. J Clin Oncol 2003; 21:2600

Metastatic DiseaseMetastatic Disease

<10% patients at presentation <10% patients at presentation Eventually develops inEventually develops in– 1/31/3rdrd of node negative patients of node negative patients– >50% of node positive patients>50% of node positive patients

No curative therapy availableNo curative therapy availableAverage survival ~18-24 monthsAverage survival ~18-24 months

Goldstein L: ASCO Edu Sess June 2003Stockler M et al. Cancer Treat Reviews 2000; 26:151

Chemotherapy Indications in Chemotherapy Indications in Metastatic DiseaseMetastatic Disease

Unresponsive disease to endocrine Unresponsive disease to endocrine therapytherapyRapidly progressive diseaseRapidly progressive diseaseVisceral involvement?Visceral involvement?Life threatening diseaseLife threatening disease

ChemotherapyChemotherapy

No single gold standardNo single gold standardIndividualize therapy Individualize therapy Sequential single agents Sequential single agents ororCombination chemotherapyCombination chemotherapyVariety of acceptable optionsVariety of acceptable options

New Drugs for Breast CancerNew Drugs for Breast CancerCytotoxicsCytotoxics EndocrineEndocrine BisphosphonatesBisphosphonates ST InhibitorST Inhibitor

PaclitaxelPaclitaxel AnastrazoleAnastrazole ClodronateClodronate TrastzumabTrastzumabDocatexalDocatexal LetrozoleLetrozole PamidronatePamidronateVinorelbineVinorelbine ExemestaneExemestane ZoledronateZoledronateCapecitabineCapecitabine ToremifeneToremifene IbandronateIbandronateGemcitabineGemcitabine GoselerineGoselerine

FulvestrantFulvestrant

Smith IE: Lancet 2002; 360:790

Combinations: FAC, FEC<, Anthra + Taxane, TAC, ATG, AV, TP, TX, GV, GP etc…

breast cancer drug therapy 2004a

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