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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
Adjuvant Systemic Therapy for Patients with Adjuvant Systemic Therapy for Patients with Operable Breast Cancer-St. Gallen 2003Operable Breast Cancer-St. Gallen 2003
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
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
HR-HR-
Risk groupRisk group PremenopausalPremenopausal PostmenopausalPostmenopausal
Node negativeNode negative ChemotherapyChemotherapy ChemotherapyChemotherapy
Node positiveNode positive ChemotherapyChemotherapy ChemotherapyChemotherapy
Goldhirsch A et al: Meeting highlights. J Clin Oncol 2003;21:3357
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
Goss et al. N Engl J Med. 2003;349:1793-1802.
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
Goss et al. N Engl J Med. 2003;349:1793-1802.
• 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
Goss et al. N Engl J Med. 2003;349:1793-1802.
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
Goss et al. N Engl J Med. 2003;349:1793-1802.
Coombs RC et al. N Engl J Med 2004; 350:1081
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%
EBCTG: Lancet 1992; 339:1
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
EBCTG: Lancet 1992; 339:1
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
Lohrisch C et al: Eur J Cancer 2001; 37 (s7):45
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
Lohrisch C et al: Eur J Cancer 2001; 37 (s7):45
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
Adjuvant Medical TherapyAdjuvant Medical Therapy
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
Adjuvant Medical TherapyAdjuvant Medical Therapy
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…