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Adjuvant Treatment in
Breast Cancer
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Variables for Prognosis
of Early Breast Cancer and for
Adjuvant Treatment
1. Axillary Lymph Node Status
2. Estrogen Receptor
3. Her-2/neu Status
4. Treatment
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Treatment
Modalities for Breast Cancer
* Neoadjuvant Treatment
* Adjuvant Treatment
* Palliative Treatment
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Variables for Decision
of Adjuvant Therapy
Node-Negative / -Positive
Adjuvant
Therapy
ER-Positive / -Negative
HER-2 as Predictive Marker
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy of
Early Breast Cancer
A. Endocrine Interventions
Ovarian Ablation
Tamoxifen
Aromatase Inhibitors
B. Polychemotherapy
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Effects of Adjuvant Therapy
for Early Breast Cancer: 1990 - .
Treatment
A. Endocrine Interventions
Ovarian Ablation
Effectivity
10% Absolute Gain in 15 yr.-Survival
Tamoxifen
8% Absolute Gain in 15 yr.-Survival
50% Reduction in Contralateral cancer
Small Risk of Endometrial Cancer, DVT
Aromatase Inhibitors
First Data (47 Months Follow-Up)
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy in Patients with
Breast Cancer:
Unresolved Questions 2003.
A. ENDOCRINE TREATMENT
1. Role of hormone withdrawal in premenopausal
patients.
2. Role of third generation aromatase inhibitors in
postmenopausal patients.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
The Estrogen Receptor in
Breast Cancer
1. Localised within the Tumour Cell.
2. Interaction with Estrogen Results in Signal
Transduction and Tumour Cell Proliferation.
3. Blockade Results in Cancer Cell Death.
Consequence No. 1: Competitive Inhibition of
Estrogen.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Reduction of Relapses and Mortality
from Early Breast Cancer by 20 mg
Tamoxifen for 5 Years. *
Reduction of
Relapse
Mortality
2p
42  3%
22  4%
<.00001/.00001
Clinical Division of Oncology
Department of Medicine I
* EBCTCG, LANCET 351: 1451, 1998
Medical University of
Vienna, Austria
Estrogen Withdrawal Modalities
1. Premenopausal Patients
LH-RH Agonists
+ Tamoxifen
(+ Aromatase Inhibitors?)
2. Postmenopausal Patients
Aromatase Inhibitors
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Effectivity of Estrogen Withdrawal in
Premenopausal Patients with Stage I
and II EBC: The ABCSG Trial. *
1.034 Premenopausal Patients
Hormone-Responsive Disease
Treatment:
3 yrs. Goserelin plus 5 yrs. Tamoxifen
vs.
6 Cycles of CMF
Analysis at 60-month Median Follow-Up
Clinical Division of Oncology
Department of Medicine I
* R. Jakesz et al., J. Clin. Oncol. 20: 4621-4627,
2002
Medical University of
Vienna, Austria
Effectivity of Estrogen Withdrawal in
Premenopausal Patients with Stage I
and II EBC: The ABCSG Trial. *
Treatment
Relapses
Endocrine
Cytotoxic
17.2%
20.8%
4.7%
8.0%
81%
76%
p
0.0176
0.0029
0.037
Clinical Division of Oncology
Department of Medicine I
Local Recurrences
* R. Jakesz et al., J. Clin. Oncol. 20: 4621-4627,
2002
RFS at 5 yrs.
Medical University of
Vienna, Austria
Effectivity of Estrogen Withdrawal in
Premenopausal Patients with Stage I
and II EBC: The ABCSG Trial. *
CONCLUSION
„The Goserelin-Tamoxifen Combination is
Significantly More Effective than CMF in
Premenopausal Patients with Stage I and II
ER-Positive EBC.“
Clinical Division of Oncology
Department of Medicine I
* R. Jakesz et al., J. Clin. Oncol. 20: 4621-4627,
2002
Medical University of
Vienna, Austria
Effectivity of Estrogen Withdrawal in
Premenopausal Patients with Stage II
EBC: The ZEBRA Trial. *
Study Design
1640 Randomized Patients
Goserelin for 2 Years (n=817)
vs.
6x CMF (n=823)
ER-Positive and ER-Negative Patients
Median Follow-Up: 6 Years.
Clinical Division of Oncology
Department of Medicine I
* W. Jonat et al., J. Clin. Oncol. 20: 4628-4635,
2002
Medical University of
Vienna, Austria
Effectivity of Estrogen Withdrawal in
Premenopausal Patients with Stage
II EBC: The ZEBRA Trial. *
Primary Efficacy of Goserelin vs. CMF
DFS
ER-positive
ER-negative
ER-unknown
p=0.94 (equal efficacy)
p=0.0006 in favor of CMF
p=0.026 in favor of CMF
Clinical Division of Oncology
Department of Medicine I
OS
p=0.92 (equal efficacy)
p=0043 in favor of CMF
p=0.14
* W. Jonat et al., J. Clin. Oncol. 20: 4628-4635,
2002
Medical University of
Vienna, Austria
Effectivity of Estrogen Withdrawal in
Premenopausal Patients with Stage II
EBC: The ZEBRA Trial. *
CONCLUSION
„Equal Efficacy of Goserelin Given for
2 Years and 6 Cycles of CMF in
Patients with ER-Positive
Stage II Breast Cancer.“
Clinical Division of Oncology
Department of Medicine I
* W. Jonat et al., J. Clin. Oncol. 20: 4628-4635,
2002
Medical University of
Vienna, Austria
Effectivity of Estrogen Withdrawal in
Postmenopausal Patients with EBC:
Design of the ATAC Trial* .
Anastrozole (n=3125) vs.
Tamoxifen (n=3116) vs.
Anastrozole + Tamoxifen (n=3125)
Median follow-up: 47 months for DFS
Clinical Division of Oncology
Department of Medicine I
* Arimidex, Tamoxifen, Alone or in Combination; A.
Buzdar SABCC 2002, Abstr. #13
Medical University of
Vienna, Austria
Effectivity of Estrogen Withdrawal in
Postmenopausal Patients with EBC:
Results of the ATAC Trial*.
Significance Anastrozole vs. Tamoxifen in ER+ Patients
DFS Estimates at 4 Years
Disease-free Survival
Time to Recurrence
Contralateral Breast Cancer
89% vs. 86.1%
0.014
0.007
0.042
NB: Results of Anastrozole + Tamoxifen equal to Tamoxifen alone!
Clinical Division of Oncology
Department of Medicine I
* Arimidex, Tamoxifen, Alone or in Combination; A.
Buzdar SABCC 2002, Abstr. #13
Medical University of
Vienna, Austria
Side Effects of Anastrozole vs.
Tamoxifen in the ATAC Trial*.
Hot Flushes
Vaginal Bleeding and Discharge
Thromboembolic Events
Ischemic Cerebrovascular Event
Endometrial Cancer
p<0.0001 in favor of Anastrozole
p<0.0001 in favor of Anastrozole
p=0.0006 in favor of Anastrozole
p=0.0006 in favor of Anastrozole
p=0.02 in favor of Anastrozole
Osteoporotic Bone Fractures
Musculoskeletal Disorders
p<0.0001 in favor of Tamoxifen
p<0.0001 in favor of Tamoxifen
Clinical Division of Oncology
Department of Medicine I
* The ATAC Trialists´ Group: Lancet 359: 21312139, 2002
Medical University of
Vienna, Austria
Endocrine Adjuvant Treatment of
Early Breast Cancer in
Premenopausal Patients.
Nodal Status
ER+
ER-
N0
Goserelin +/- Tamoxifen
Chemotherapy
N1
Chemotherapy
Tamoxifen
(Goserelin + Tamoxifen)
Chemotherapy
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Endocrine Adjuvant Treatment of
Early Breast Cancer in
Postmenopausal Patients.
Nodal Status
ER+
ER-
N0
Tamoxifen
(Aromatase Inhibitor)
Chemotherapy
N1
Tamoxifen
+/- Chemotherapy
(Aromatase Inhibitor)
Chemotherapy
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Chemotherapy in
Early Breast Cancer. *
REDUCTION OF ANNUAL RISK OF
RELAPSE AND DEATH BY
CHEMOTHERAPY
RELAPSE
DEATH
Clinical Division of Oncology
Department of Medicine I
-23.5  2.1%
-15.3  2.4%
* EBCTCG, LANCET 352: 930, 1998.
<.00001
<.00001
Medical University of
Vienna, Austria
Early Breast Cancer Trialists Collaborative
Group: Effect of Adjuvant AnthracyclineBased Chemotherapy: Reduction of Annual
Hazards. *
% of Reduction
2p
Anthracycline-Based Chemotherapy vs. CMF
Recurrences
Mortality
Clinical Division of Oncology
Department of Medicine I
12  4
11  5
* EBCTCG, Lancet 352: 930, 1998.
<.006
<.02
Medical University of
Vienna, Austria
Adjuvant Polychemotherapy
for Early Breast Cancer: 1990 - .
Premenopausal Patients:
5-12% Absolute Gain in 10 yr.-Survival
Postmenopausal Patients:
2-4% Absolute Gain in 10 yr.-Survival
Clinical Division of Oncology
Department of Medicine I
NIH 2000 Consensus Conference
Medical University of
Vienna, Austria
Anthracyclines in
Adjuvant Therapy for Early
Breast Cancer.
Additional Absolute Gain
in OS with Anthracycline
-Based Chemotherapy
Clinical Division of Oncology
Department of Medicine I
5 Years
10 Years
1.7%
in N- Pats.
4%
in N+ Pats.
NIH 2000 Consensus Conference
Medical University of
Vienna, Austria
Simulation of Impact of Adjuvant
Chemotherapy in EBC.
% Free of Recurrence
100
Annual Odds
of Recurrence:
80
60
Nil = 15% / Yr.
CMF = 11.4% / Yr.
(Reduced by 24%)
40
AC
CMF
Nil
20
AC = 10% / Yr.
(Reduced by 12%)
0
0
2
Clinical Division of Oncology
Department of Medicine I
4
Years
6
8
10
Medical University of
Vienna, Austria
Adjuvant Therapy in Patients
with Breast Cancer: Unresolved
Questions 2003.
B. CHEMOTHERAPY
1. Role of Anthracyclines.
2. Role of Taxanes.
3. Dose density.
4. Combination with Endocrine Treatment.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Anthracyclines in the Adjuvant
Therapy of Patients with Breast
Cancer: Unresolved Questions 2003.
1. When is an Anthracycline-Based Regimen Preferable to CMF?
2. Which Anthracycline Should be Used?
3. Which Regimen? 2- or 3-Drug-Regimen? Dose? Schedule?
4. How Many Cycles? 4 or 6?
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Review of Anthracyclines in the Adjuvant
Chemotherapy of Breast Cancer: The
Dilemma.
Authors
Cytotoxics
Results
Fisher et al. 1989 (B-11)
Fisher et al. 1990 (B-15)
Moliterini et al. 1991
Budd et al. 1995
Misset et al. 1996
Coombes et al. 1996
Levine et al. 1998
Mouridsen et al. 1999
Piccart et al. 2001
PF(T) vs. PAF(T)
CMF (6Mo.) vs. AC (2Mo.)
CMF vs. CMF->A
CMFVP vs. FAC-M
CMF vs. AVCF
CMF vs. FEC
CMF vs. CEF
CMF vs. CEF
CMF vs. EC
Sign. OS&DFS for PAF vs. PF
n.s.
n.s. for DFS & OS
Sign. DFS for CMFVP
Sign. OS & DFS Premenopause
Sign. OS & DFS Premenopause
Sig. OS & DFS Premenopause
Sign. OS Premenopause
No Advantage of EC vs. CMF
Reconfirmation of Dose
Response
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Effectivity of AnthracyclineBased Adjuvant Chemotherapy
in Breast Cancer.
Effectivity Analysed in Premenopausal Patients Only
Misset et al. 1996
Levine et al. 1998
Mouridsen et al. 1999
No Advantage for Postmenopausal Patients
Misset et al. 1996
Piccart et al. 2001 (41-44% Postmenopausal Patients Included)
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Chemotherapy of
Primary Breast Cancer:
Some general remarks...
• Adriamycin Doses < 40mg/m2 are Inferior to 60
mg/m2 (CALGB 8541).
• Cyclophosphamide Doses > 600 mg/m2 are not
Superior (NSABP B-22).
• Chemotherapy Seems More Effective in ER- Than ER+
Disease (EBCTCG).
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy with Anthracyclines in
Patients with Breast Cancer:
Dose Recommendations.
DRUG
PUBLICATION
RECOMMENDATION
Adriamycin CALGB 9344
60mg/m2 q. 3 wks. in the AC Regimen
Epirubicin French Trial
Belgian Trial
100mg/m2 q. 3 wks. in the EC and
FEC regimens for high risk (N+)
women
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Efficacy of Anthracycline-Based
Adjuvant Chemotherapy in Her-2/neu
Overexpressing Early Breast Cancer.
STUDY
AUTHOR
NSABP-B11
(PF vs. PAF)
PAIK et al. 1998
NSABP-B15
PAIK et al. 2000
(AC vs. CMF vs. AC->CMF)
Clinical Division of Oncology
Department of Medicine I
RESULTS IN HER-2/neu
POSITIVE
NEGATIVE
DFS & OS SIGN.
(Advantage Anthracycline)
n.s.
DFS & OS BORDERLINE
(Advantage Anthracycline)
n. s.
Medical University of
Vienna, Austria
Proposed Algorithm for Anthracycline
Use as Adjuvant Therapy in Patients
with Breast Cancer.
ENDOCRINE RESPONSIVE
Likelihood of Response
Low
High
FE(A)C d1 x6
CE(A)F d1+8 x6
ENDOCRINE-NON-RESPONSIVE
Risk Profile
Average
High
AC x4
FE(A)C d1 x6
CE(A)F d1+8 x6
? Her-2/neu +++
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy with
Anthracyclines in Patients with
Breast Cancer: Conclusions.
The use of anthracyclines increases DFS and OS, probably
even more so in selected patient populations
(premenopause, Her-2/neu overexpression, etc.), and is
superior to CMF.
The routine use of anthracycline-based regimens is
recommended in appropriate patient populations, optimal
schedule and frequency of administration, however, are
not clear at the moment.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy in Patients
with Breast Cancer: Unresolved
Questions 2003.
Role of Taxanes
Available Studies:
CALGB 9344
NSABP-B27
NSABP-B28
BCIRG 001
M.D. ANDERSON
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Role of PACLITAXEL in Adjuvant
Chemotherapy of Patients with LymphnodePositive Breast Cancer
(CALGB 9344): RATIONALE. *
1. AC most active adjuvant chemotherapy.
2. Paclitaxel achieves responses in stage IV breast cancer in 5259% of patients
(22-30% in anthraycyline resistant patients)
3. Sequential chemotherapy is reasonable.
Clinical Division of Oncology
Department of Medicine I
* I.C. Henderson et al., Proc. ASCO 17: 390A,
1998.
Medical University of
Vienna, Austria
Paclitaxel-induced Apopotosis is
Independent from p53 Mutation
Status. *
Paclitaxel-induced Apoptosis is
 Dependent on
ERK
p38 MAP Kinase Cascades
 Independent from
p53
Clinical Division of Oncology
Department of Medicine I
* BACUS et al., Oncogene 20: 147, 2001
Medical University of
Vienna, Austria
Role of PACLITAXEL in Adjuvant
Chemotherapy of Patients with NodePositive Breast Cancer (CALGB 9344)
THERAPY
Doxorubicin 60, 75 or 90mg/m2 + Cyclophosphamide (AC) x 4,
then randomised to
nil vs.
sequential Paclitaxel (175mg/m2) x 4 (+/- Tamoxifen 20mg, 5 Years)
PATIENTS
3.170 Patients
Randomised according to 3x2 factorial trial design
Positive axillary lymph nodes (1 - >10 Lnn.),
First Kaplan-Meier Analysis after 18 months
Clinical Division of Oncology
Department of Medicine I
* I.C. Henderson et al., Proc. ASCO 17: 390A,
1998.
Medical University of
Vienna, Austria
Role of PACLITAXEL in Adjuvant
Chemotherapy of Patients with NodePositive Breast Cancer (CALGB 9344): First
Results. *
AC
AC->T
p
DFS
86  1.2%
90  1%
(= 22% Reduction of Relapses)
0.0077
OS
95  0.7%
97  0.6%
(= 26% Reduction of Mortality)
0.039
Clinical Division of Oncology
Department of Medicine I
* I.C. Henderson et al., Proc. ASCO 17: 390A,
1998.
Medical University of
Vienna, Austria
Role of PACLITAXEL in Adjuvant
Chemotherapy of Patients with NodePositive Breast Cancer (CALGB 9344):
Results January 2003. *
Overall Survival
Survival Receptor Positive Tumours
Survival Receptor Negative Tumors
p
0.01
0.4808
0.0034
Disease Free Survival (DFS)
DFS Receptor Positive Tumors
DFS Receptor Negative Tumors
0.0018
0.2501
0.0006
Clinical Division of Oncology
Department of Medicine I
* L. Norton, tAnGo Trialists‘ Meeting January
2003
Medical University of
Vienna, Austria
CALGB 9344: TOXICITY. *
Diagnosis
% Patients
Transient Myelosuppression
Chemotherapy-associated Cardiotoxicity
Neuropathy
Pain
Hyperglycemia
Clinical Division of Oncology
Department of Medicine I
* I.C. Henderson et al., Proc. ASCO 17: 390A,
1998.
21
6
5
5
5
Medical University of
Vienna, Austria
The NSABP B-28 Trial: Paclitaxel for
Adjuvant Treatment of Breast Cancer.
Sequential AC T
3060 Node-Positive Patients
Median Follow-Up: 34 Months
NO SURVIVAL ADVANTAGE
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
The MD Anderson Trial on Paclitaxel
for Adjuvant Treatment of Breast Cancer.
Sequential P
FAC
524 Patients
Median Follow-Up: 43 Months
NO SURVIVAL ADVANTAGE
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Phase III Trial Comparing TAC with FAC in
the Treatment of Node Positive Breast
Cancer: Interim Analysis of BCIRG 001
Study. *
Median Observation: 33 Months
TAC (745 Patients)
Taxotere (75mg/m2), Doxorubicin (50mg/m2),
Cyclophosphamide (500mg/m2)
FAC (746 Patients)
Fluorouracil (500mg/m2), Doxorubicin (50mg/m2),
Cyclophosphamide (500mg/m2)
q. 21 Days x6
ER-Positivity: Tamoxifen for 5 Years
Clinical Division of Oncology
Department of Medicine I
* J.M. Nabholtz et al., Proc. Am. Soc. Clin. Oncol.
21: 141, 2002
Medical University of
Vienna, Austria
Phase III Trial Comparing TAC with FAC in
the Treatment of Node Positive Breast
Cancer: Interim Analysis of
BCIRG 001 Study. *
TAC vs. FAC
P-VALUE
Disease Free Survival
Adjusted for Nodal Status
1-3 Nodes
4+ Nodes
0.68
0.50
0.86
0.0011
0.0002
0.33
Overall Survival
Adjusted for Nodal Status
1-3 Nodes
4+ Nodes
0.76
0.46
1.08
0.11
0.006
0.75
Clinical Division of Oncology
Department of Medicine I
* J.M. Nabholtz et al., Proc. Am. Soc. Clin. Oncol.
21: 141, 2002
Medical University of
Vienna, Austria
Phase III Trial Comparing TAC with FAC in
the Treatment of Node-Positive Breast
Cancer (BCIRG 001 STUDY): Toxicity. *
Febrile Neutropenia
Neutropenia Grades 3/4
Septic Deaths
Nausea / Vomitus Grades 3/4
Asthzenia
Stomatitis
Cardiomyopathy
Clinical Division of Oncology
Department of Medicine I
TAC
FAC
24%
3%
0
n.a.
11%
7%
1%
2%
1%
0
16%
5%
n.a.
0.1%
* J.M. Nabholtz et al., Proc. Am. Soc. Clin.
Oncol. 21: 141, 2002
Medical University of
Vienna, Austria
The NSABP B-27 Trial: Efficacy
of Docetaxel in Adjuvant
Treatment of Breast Cancer.
Sequential AC
D, Neoadjuvant
2411 T1-T3 Patients with Operable Breast Cancer
Median Follow-Up: 39 Months
TOO EARLY FOR DFS AND OS
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy in Patients with Breast
Cancer: Unresolved Questions 2003.
Role of Taxanes
…. is unclear, yet
…. side effects?
…. possible benefit weighed against risks
…. in clinical trials only
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy in Patients with Breast
Cancer: Unresolved Questions 2003.
DOSE DENSITY
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
“Normal” Dose Intensity vs.
Increased Dose Density
1012
1010
108
106
104
102
1
0
Clinical Division of Oncology
Department of Medicine I
1
2
3
4
5
6
7
Medical University of
Vienna, Austria
Sequential Therapy is
Dose Dense.
1012
1010
108
106
104
102
1
0
Clinical Division of Oncology
Department of Medicine I
1
2
3
Months
4
5
6
7
Medical University of
Vienna, Austria
Intergroup/CALGB 9741:
Node-Positive Stage II-IIIA
3-Week Cycles
2-Week Cycles (w/ G-CSF)
Doxorubicin (A) 60 mg/m2
Paclitaxel (T) 175 mg/m2
Clinical Division of Oncology
Department of Medicine I
Cyclophosphamide (C) 600 mg/m2
Medical University of
Vienna, Austria
CALGB 9741: 3-YEAR RESULTS OF DOSE-DENSITY
vs. CONVENTIONAL DOSE AND SEQUENTIAL vs.
COMBINATION CHEMOTHERAPY, 2205 PATIENTS
WITH N+ DISEASE. *
TREATMENT
TREATMENT DURATION
q. 2 wks. + G-CSF
q. 3 wks.
SEQUENTIAL A-T-C x4, resp.
CONCURRENT AC T x4, resp.
24 wks.
16 wks.
36 wks.
24 wks.
DISEASE-FREE SURVIVAL
OVERALL SURVIVAL
82%
92%
75%
90%
Clinical Division of Oncology
Department of Medicine I
* CITRON et al., SABCC 2002
p=0.007
p=0.014
Medical University of
Vienna, Austria
Adjuvant Therapy in Patients with Breast
Cancer: Unresolved Questions 2003.
INCREASE IN DOSE DENSITY
…. Exciting, but not for Routine Use
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy in Patients with Breast
Cancer: Unresolved Questions 2003.
CHEMOTHERAPY PLUS ENDOCRINE TREATMENT
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
REDUCTION OF RECURRENCE AND
MORTALITY BY TAMOXIFEN AND
CHEMOTHERAPY IN BREAST CANCER.*
% REDUCTION OF
RECURRENCE
MORTALITY
5 YEARS TAMOXIFEN vs. 0
-46  4
-22  5
5 YEARS TAMOXIFEN + CHEMOTHERAPY
vs. CHEMOTHERAPY
-52  8
-47  9
Clinical Division of Oncology
Department of Medicine I
* EBCTCG, LANCET 351: 1451, 1998
Medical University of
Vienna, Austria
Sequence of Chemotherapy and
Tamoxifen in Early Breast Cancer.
INT 0100 TRIAL
(n=1116)
GEICAM TRIAL
(n=485)
Median Follow-Up
Chemotherapy
8 Years
CAF x6
4.5 Years
EC x4
Disease-Free Survival
CTX
T
CTX + T
p-Value
67%
62%
0.03
64%
57%
n.s.
Toxicities
Overall Survival
No Difference
No Difference
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy in Patients with
Breast Cancer: Unresolved
Questions 2003.
COMBINED CHEMOTHERAPY AND ENDOCRINE TREATMENT
…. should be Administered Sequentially
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Effectivity of Adjuvant Chemotherapy
in Breast Cancer: Conclusion and
Review of Conflicting Issues.
1. Polychemotherapy significantly reduces the annual
risk of relapse and mortality both for N0- as well as N1breast cancers.
2. Anthracycline-based regimens have been shown to
have a significant advantage over non-anthracyclineregimens in premenopausal patients.
3. Use of taxanes continues to be controversial.
4. Dose density is becoming a decisive issue and
deserves attention in future trials.
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria
Adjuvant Therapy in Breast Cancer:
Final Conclusion.
Recruit Patients into Clinical Trials!
Clinical Division of Oncology
Department of Medicine I
Medical University of
Vienna, Austria