Adjuvant Treatment in Breast Cancer

Clinical Division of OncologyDepartment of Medicine I

Medical University ofVienna, Austria

Adjuvant Treatment in Adjuvant Treatment in Breast CancerBreast Cancer



Variables for PrognosisVariables for Prognosisof Early Breast Cancer and for of Early Breast Cancer and for

Adjuvant TreatmentAdjuvant Treatment

1. Axillary Lymph Node Status

2. Estrogen Receptor

3. Her-2/neu Status

4. Treatment



* Neoadjuvant Treatment * Adjuvant Treatment * Palliative Treatment

Treatment Treatment Modalities for Breast CancerModalities for Breast Cancer



Variables for Decision Variables for Decision of Adjuvant Therapy of Adjuvant Therapy

Adjuvant Adjuvant TherapyTherapy

Node-Negative / -PositiveNode-Negative / -Positive

ER-Positive / -NegativeER-Positive / -Negative

HER-2 as Predictive MarkerHER-2 as Predictive Marker



Adjuvant Therapy of Adjuvant Therapy of Early Breast CancerEarly Breast Cancer

A. Endocrine InterventionsOvarian AblationTamoxifenAromatase Inhibitors

B. Polychemotherapy



Effects of Adjuvant Therapy Effects of Adjuvant Therapy for Early Breast Cancer: 1990 - .for Early Breast Cancer: 1990 - .

Treatment Effectivity

A. Endocrine InterventionsOvarian Ablation 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)



A. ENDOCRINE TREATMENT

1. Role of hormone withdrawal in premenopausal patients.

2. Role of third generation aromatase inhibitors in postmenopausal patients.

Adjuvant Therapy in Patients with Adjuvant Therapy in Patients with Breast Cancer: Breast Cancer:

Unresolved Questions 2003.Unresolved Questions 2003.



The Estrogen Receptor in The Estrogen Receptor in Breast CancerBreast 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.



Reduction of Relapses and Mortality Reduction of Relapses and Mortality from Early Breast Cancer by 20 mg from Early Breast Cancer by 20 mg

Tamoxifen for 5 Years. *Tamoxifen for 5 Years. *

Relapse Mortality 2p

42 3% 22 4% <.00001/.00001

* EBCTCG, LANCET 351: 1451, 1998

Reduction of



Estrogen Withdrawal Modalities

1. Premenopausal PatientsLH-RH Agonists+ Tamoxifen(+ Aromatase Inhibitors?)

2. Postmenopausal PatientsAromatase Inhibitors



Effectivity of Estrogen Withdrawal in Effectivity of Estrogen Withdrawal in Premenopausal Patients with Stage I Premenopausal Patients with Stage I

and II EBC: The ABCSG Trial. *and II EBC: The ABCSG Trial. *

1.034 Premenopausal PatientsHormone-Responsive DiseaseTreatment:

3 yrs. Goserelin plus 5 yrs. Tamoxifenvs.

6 Cycles of CMF

Analysis at 60-month Median Follow-Up

* R. Jakesz et al., J. Clin. Oncol. 20: 4621-4627, 2002





Treatment Relapses Local Recurrences RFS at 5 yrs.

Endocrine 17.2% 4.7% 81%

Cytotoxic 20.8% 8.0% 76%

p 0.0176 0.0029 0.037






CONCLUSION

„The Goserelin-Tamoxifen Combination is Significantly More Effective than CMF in

Premenopausal Patients with Stage I and II ER-Positive EBC.“




Effectivity of Estrogen Withdrawal in Effectivity of Estrogen Withdrawal in Premenopausal Patients with Stage II Premenopausal Patients with Stage II

EBC: The ZEBRA Trial. *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 PatientsMedian Follow-Up: 6 Years.

* W. Jonat et al., J. Clin. Oncol. 20: 4628-4635, 2002



Effectivity of Estrogen Withdrawal in Effectivity of Estrogen Withdrawal in Premenopausal Patients with Stage Premenopausal Patients with Stage

II EBC: The ZEBRA Trial. *II EBC: The ZEBRA Trial. *

Primary Efficacy of Goserelin vs. CMF

DFS OS

ER-positive p=0.94 (equal efficacy) p=0.92 (equal efficacy)

ER-negative p=0.0006 in favor of CMF p=0043 in favor of CMF

ER-unknown p=0.026 in favor of CMF p=0.14




Effectivity of Estrogen Withdrawal in Effectivity of Estrogen Withdrawal in Premenopausal Patients with Stage II Premenopausal Patients with Stage II

EBC: The ZEBRA Trial. *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.“




Effectivity of Estrogen Withdrawal in Effectivity of Estrogen Withdrawal in Postmenopausal Patients with EBC: Postmenopausal Patients with EBC:

Design of the ATAC Trial* .Design of the ATAC Trial* .

Anastrozole (n=3125) vs.Tamoxifen (n=3116) vs.Anastrozole + Tamoxifen (n=3125)

Median follow-up: 47 months for DFS

* Arimidex, Tamoxifen, Alone or in Combination; A. Buzdar SABCC 2002, Abstr. #13



Effectivity of Estrogen Withdrawal in Effectivity of Estrogen Withdrawal in Postmenopausal Patients with EBC: Postmenopausal Patients with EBC:

Results of the ATAC Trial*.Results of the ATAC Trial*.

Significance Anastrozole vs. Tamoxifen in ER+ Patients

DFS Estimates at 4 Years 89% vs. 86.1%Disease-free Survival 0.014Time to Recurrence 0.007Contralateral Breast Cancer 0.042

NB: Results of Anastrozole + Tamoxifen equal to Tamoxifen alone!

* Arimidex, Tamoxifen, Alone or in Combination; A. Buzdar SABCC 2002, Abstr. #13



Side Effects of Anastrozole vs. Side Effects of Anastrozole vs. Tamoxifen in the ATAC Trial*.Tamoxifen in the ATAC Trial*.

Hot Flushes p<0.0001 in favor of AnastrozoleVaginal Bleeding and Discharge p<0.0001 in favor of AnastrozoleThromboembolic Events p=0.0006 in favor of AnastrozoleIschemic Cerebrovascular Event p=0.0006 in favor of AnastrozoleEndometrial Cancer p=0.02 in favor of Anastrozole

Osteoporotic Bone Fractures p<0.0001 in favor of TamoxifenMusculoskeletal Disorders p<0.0001 in favor of Tamoxifen

* The ATAC Trialists´ Group: Lancet 359: 2131-2139, 2002



Endocrine Adjuvant Treatment of Endocrine Adjuvant Treatment of

Early Breast Cancer in Early Breast Cancer in Premenopausal Patients.Premenopausal Patients.

Nodal Status ER+ ER-

N0 Goserelin +/- TamoxifenChemotherapy

N1 Chemotherapy TamoxifenChemotherapy

(Goserelin + Tamoxifen)



Endocrine Adjuvant Treatment of Endocrine Adjuvant Treatment of Early Breast Cancer in Early Breast Cancer in

Postmenopausal Patients.Postmenopausal Patients.

Nodal Status ER+ ER-

N0 Tamoxifen Chemotherapy(Aromatase Inhibitor)

N1 Tamoxifen Chemotherapy+/- Chemotherapy(Aromatase Inhibitor)



Adjuvant Chemotherapy in Adjuvant Chemotherapy in Early Breast Cancer. *Early Breast Cancer. *

RELAPSE -23.5 2.1% <.00001 DEATH -15.3 2.4% <.00001

* EBCTCG, LANCET 352: 930, 1998.

REDUCTION OF ANNUAL RISK OF RELAPSE AND DEATH BY

CHEMOTHERAPY



Early Breast Cancer Trialists Collaborative Early Breast Cancer Trialists Collaborative Group: Effect of Adjuvant Anthracycline-Group: Effect of Adjuvant Anthracycline-

Based Chemotherapy: Reduction of Annual Based Chemotherapy: Reduction of Annual Hazards. *Hazards. *

% of Reduction 2p

Anthracycline-Based Chemotherapy vs. CMF

Recurrences 12 4 <.006 Mortality 11 5 <.02

* EBCTCG, Lancet 352: 930, 1998.



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

NIH 2000 Consensus Conference



Anthracyclines in Anthracyclines in Adjuvant Therapy for Early Adjuvant Therapy for Early

Breast Cancer.Breast Cancer.

5 Years 10 Years

Additional Absolute Gain 1.7% 4%in OS with Anthracycline in N- Pats. in N+ Pats.-Based Chemotherapy

NIH 2000 Consensus Conference



% F

ree

of

Rec

urr

ence

Years

Simulation of Impact of Adjuvant Simulation of Impact of Adjuvant Chemotherapy in EBC.Chemotherapy in EBC.

Annual Odds of Recurrence:

Nil = 15% / Yr.

CMF = 11.4% / Yr. (Reduced by 24%)

AC = 10% / Yr. (Reduced by 12%)

0

20

40

60

80

100

0 2 4 6 8 10

AC

CMF

Nil



B. CHEMOTHERAPY

1. Role of Anthracyclines. 2. Role of Taxanes. 3. Dose density.

4. Combination with Endocrine Treatment.

Adjuvant Therapy in Patients Adjuvant Therapy in Patients with Breast Cancer: Unresolved with Breast Cancer: Unresolved

Questions 2003.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?

Anthracyclines in the Adjuvant Anthracyclines in the Adjuvant Therapy of Patients with Breast Therapy of Patients with Breast

Cancer: Unresolved Questions 2003.Cancer: Unresolved Questions 2003.



Review of Anthracyclines in the Adjuvant Review of Anthracyclines in the Adjuvant Chemotherapy of Breast Cancer: The Chemotherapy of Breast Cancer: The

Dilemma.Dilemma.

Authors Cytotoxics Results

Fisher et al. 1989 (B-11) PF(T) vs. PAF(T) Sign. OS&DFS for PAF vs. PF Fisher et al. 1990 (B-15) CMF (6Mo.) vs. AC (2Mo.) n.s.Moliterini et al. 1991 CMF vs. CMF->A n.s. for DFS & OSBudd et al. 1995 CMFVP vs. FAC-M Sign. DFS for CMFVPMisset et al. 1996 CMF vs. AVCF Sign. OS & DFS PremenopauseCoombes et al. 1996 CMF vs. FEC Sign. OS & DFS PremenopauseLevine et al. 1998 CMF vs. CEF Sig. OS & DFS PremenopauseMouridsen et al. 1999 CMF vs. CEF Sign. OS PremenopausePiccart et al. 2001 CMF vs. EC No Advantage of EC vs. CMF

Reconfirmation of Dose Response



Effectivity of Anthracycline-Effectivity of Anthracycline-

Based Adjuvant Chemotherapy Based Adjuvant Chemotherapy in Breast Cancer.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)



Adjuvant Chemotherapy of Adjuvant Chemotherapy of Primary Breast Cancer: Primary Breast Cancer: Some general remarks...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).



DRUG PUBLICATION RECOMMENDATION

Adriamycin CALGB 9344 60mg/m2 q. 3 wks. in the AC Regimen

Epirubicin French Trial 100mg/m2 q. 3 wks. in the EC and Belgian Trial FEC

regimens for high risk (N+) women

Adjuvant Therapy with Anthracyclines in Adjuvant Therapy with Anthracyclines in Patients with Breast Cancer: Patients with Breast Cancer:

Dose Recommendations.Dose Recommendations.



Efficacy of Anthracycline-Based Efficacy of Anthracycline-Based Adjuvant Chemotherapy in Her-2/neu Adjuvant Chemotherapy in Her-2/neu Overexpressing Early Breast Cancer.Overexpressing Early Breast Cancer.

STUDY AUTHOR RESULTS IN HER-2/neu POSITIVE NEGATIVE

NSABP-B11 PAIK et al. 1998 DFS & OS SIGN. n.s.(PF vs. PAF) (Advantage Anthracycline)

NSABP-B15 PAIK et al. 2000 DFS & OS BORDERLINE n. s.(AC vs. CMF vs. AC->CMF) (Advantage Anthracycline)



ENDOCRINE RESPONSIVE ENDOCRINE-NON-RESPONSIVE Likelihood of Response Risk Profile Low High Average High

FE(A)C d1 x6 AC x4 FE(A)C d1 x6CE(A)F d1+8 x6 CE(A)F d1+8 x6

Proposed Algorithm for Anthracycline Proposed Algorithm for Anthracycline Use as Adjuvant Therapy in Patients Use as Adjuvant Therapy in Patients

with Breast Cancer.with Breast Cancer.

? Her-2/neu +++



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.

Adjuvant Therapy with Adjuvant Therapy with Anthracyclines in Patients with Anthracyclines in Patients with

Breast Cancer: Conclusions.Breast Cancer: Conclusions.



Role of Taxanes

Available Studies:CALGB 9344NSABP-B27NSABP-B28BCIRG 001M.D. ANDERSON

Adjuvant Therapy in Patients Adjuvant Therapy in Patients with Breast Cancer: Unresolved with Breast Cancer: Unresolved




1. AC most active adjuvant chemotherapy.

2. Paclitaxel achieves responses in stage IV breast cancer in 52-59% of patients (22-30% in anthraycyline resistant patients)

3. Sequential chemotherapy is reasonable.

Role of PACLITAXEL in Adjuvant Role of PACLITAXEL in Adjuvant Chemotherapy of Patients with Chemotherapy of Patients with

Lymphnode-Positive Breast Cancer Lymphnode-Positive Breast Cancer (CALGB 9344): RATIONALE. *(CALGB 9344): RATIONALE. *

* I.C. Henderson et al., Proc. ASCO 17: 390A, 1998.



Paclitaxel-induced Apopotosis is Paclitaxel-induced Apopotosis is Independent from p53 Mutation Independent from p53 Mutation

Status. *Status. *

Paclitaxel-induced Apoptosis is

Dependent on ERK p38 MAP Kinase Cascades

Independent from p53

* BACUS et al., Oncogene 20: 147, 2001



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

Role of PACLITAXEL in Adjuvant Role of PACLITAXEL in Adjuvant Chemotherapy of Patients with Node-Chemotherapy of Patients with Node-Positive Breast Cancer (CALGB 9344)Positive Breast Cancer (CALGB 9344)




Role of PACLITAXEL in Adjuvant Role of PACLITAXEL in Adjuvant Chemotherapy of Patients with Node-Chemotherapy of Patients with Node-

Positive Breast Cancer (CALGB 9344): First Positive Breast Cancer (CALGB 9344): First Results. *Results. *


AC AC->T p

DFS 86 1.2% 90 1% 0.0077 (= 22% Reduction of Relapses)

OS 95 0.7% 97 0.6% 0.039 (= 26% Reduction of Mortality)



Role of PACLITAXEL in Adjuvant Role of PACLITAXEL in Adjuvant Chemotherapy of Patients with Node-Chemotherapy of Patients with Node-Positive Breast Cancer (CALGB 9344): Positive Breast Cancer (CALGB 9344):

Results January 2003. *Results January 2003. *

* L. Norton, tAnGo Trialists‘ Meeting January 2003

p Overall Survival 0.01Survival Receptor Positive Tumours 0.4808Survival Receptor Negative Tumors 0.0034

Disease Free Survival (DFS) 0.0018DFS Receptor Positive Tumors 0.2501DFS Receptor Negative Tumors 0.0006



CALGB 9344: TOXICITY. *CALGB 9344: TOXICITY. *


Diagnosis % Patients

Transient Myelosuppression 21 Chemotherapy-associated Cardiotoxicity 6 Neuropathy 5Pain 5 Hyperglycemia 5



The NSABP B-28 Trial: Paclitaxel for The NSABP B-28 Trial: Paclitaxel for Adjuvant Treatment of Breast Cancer.Adjuvant Treatment of Breast Cancer.

Sequential AC T

3060 Node-Positive Patients

Median Follow-Up: 34 Months

NO SURVIVAL ADVANTAGE



The MD Anderson Trial on Paclitaxel The MD Anderson Trial on Paclitaxel for Adjuvant Treatment of Breast Cancer.for Adjuvant Treatment of Breast Cancer.

Sequential P FAC

524 Patients


NO SURVIVAL ADVANTAGE



Phase III Trial Comparing TAC with FAC in Phase III Trial Comparing TAC with FAC in the Treatment of Node Positive Breast the Treatment of Node Positive Breast Cancer: Interim Analysis of BCIRG 001 Cancer: Interim Analysis of BCIRG 001

Study. *Study. *

* J.M. Nabholtz et al., Proc. Am. Soc. Clin. Oncol. 21: 141, 2002

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 x6ER-Positivity: Tamoxifen for 5 Years




TAC vs. FAC P-VALUEDisease Free SurvivalAdjusted for Nodal Status 0.68 0.00111-3 Nodes 0.50 0.00024+ Nodes 0.86 0.33

Overall Survival Adjusted for Nodal Status 0.76 0.111-3 Nodes 0.46 0.0064+ Nodes 1.08 0.75

Phase III Trial Comparing TAC with FAC in Phase III Trial Comparing TAC with FAC in the Treatment of Node Positive Breast the Treatment of Node Positive Breast

Cancer: Interim Analysis of Cancer: Interim Analysis of BCIRG 001 Study. *BCIRG 001 Study. *



Phase III Trial Comparing TAC with FAC in Phase III Trial Comparing TAC with FAC in

the Treatment of Node-Positive Breast the Treatment of Node-Positive Breast Cancer (BCIRG 001 STUDY): Toxicity. *Cancer (BCIRG 001 STUDY): Toxicity. *


TAC FAC

Febrile Neutropenia 24% 2%Neutropenia Grades 3/4 3% 1%Septic Deaths 0 0Nausea / Vomitus Grades 3/4 n.a. 16%Asthzenia 11% 5%Stomatitis 7% n.a.Cardiomyopathy 1% 0.1%



The NSABP B-27 Trial: Efficacy The NSABP B-27 Trial: Efficacy of Docetaxel in Adjuvant of Docetaxel in Adjuvant

Treatment of Breast Cancer.Treatment of Breast Cancer.

Sequential AC D, Neoadjuvant

2411 T1-T3 Patients with Operable Breast Cancer


TOO EARLY FOR DFS AND OS



Role of Taxanes

…. is unclear, yet …. side effects? …. possible benefit weighed against risks

…. in clinical trials only

Adjuvant Therapy in Patients with Breast Adjuvant Therapy in Patients with Breast Cancer: Unresolved Questions 2003.Cancer: Unresolved Questions 2003.



DOSE DENSITY

Adjuvant Therapy in Patients with Breast Cancer: Unresolved Questions 2003.



1

102

104

106

108

1010

1012

10 765432

““Normal” Dose Intensity vs. Normal” Dose Intensity vs. Increased Dose DensityIncreased Dose Density



Months

Cel

l Num

ber

1

102

104

106

108

1010

1012

10 765432

Sequential Therapy is Sequential Therapy is Dose Dense.Dose Dense.



Intergroup/CALGB 9741: Intergroup/CALGB 9741: Node-Positive Stage II-IIIANode-Positive Stage II-IIIA

Doxorubicin (A) 60 mg/m2

Paclitaxel (T) 175 mg/m2

Cyclophosphamide (C) 600 mg/m2

3-Week Cycles 2-Week Cycles (w/ G-CSF)



CALGB 9741: 3-YEAR RESULTS OF DOSE-DENSITY CALGB 9741: 3-YEAR RESULTS OF DOSE-DENSITY vs. CONVENTIONAL DOSE AND SEQUENTIAL vs. vs. CONVENTIONAL DOSE AND SEQUENTIAL vs. COMBINATION CHEMOTHERAPY, 2205 PATIENTS COMBINATION CHEMOTHERAPY, 2205 PATIENTS

WITH N+ DISEASE. *WITH N+ DISEASE. *

* CITRON et al., SABCC 2002

TREATMENT TREATMENT DURATIONq. 2 wks. + G-CSF q. 3 wks.

SEQUENTIAL A-T-C x4, resp. 24 wks. 36 wks.CONCURRENT AC T x4, resp. 16 wks. 24 wks.

DISEASE-FREE SURVIVAL 82% 75% p=0.007OVERALL SURVIVAL 92% 90% p=0.014



INCREASE IN DOSE DENSITY

…. Exciting, but not for Routine Use




CHEMOTHERAPY PLUS ENDOCRINE TREATMENT




REDUCTION OF RECURRENCE AND REDUCTION OF RECURRENCE AND

MORTALITY BY TAMOXIFEN AND MORTALITY BY TAMOXIFEN AND CHEMOTHERAPY IN BREAST CANCER.*CHEMOTHERAPY IN BREAST CANCER.*

RECURRENCE MORTALITY

5 YEARS TAMOXIFEN vs. 0 -46 4 -22 5

5 YEARS TAMOXIFEN + CHEMOTHERAPY vs. CHEMOTHERAPY -52 8 -47 9

* EBCTCG, LANCET 351: 1451, 1998

% REDUCTION OF



Sequence of Chemotherapy and Sequence of Chemotherapy and Tamoxifen in Early Breast Cancer.Tamoxifen in Early Breast Cancer.

INT 0100 TRIAL GEICAM TRIAL (n=1116) (n=485)

Median Follow-Up 8 Years 4.5 YearsChemotherapy CAF x6 EC x4

Disease-Free SurvivalCTX T 67% 64%CTX + T 62% 57%p-Value 0.03 n.s.

Toxicities No DifferenceOverall Survival No Difference



COMBINED CHEMOTHERAPY AND ENDOCRINE TREATMENT

…. should be Administered Sequentially

Adjuvant Therapy in Patients with Adjuvant Therapy in Patients with Breast Cancer: Unresolved Breast Cancer: Unresolved




Effectivity of Adjuvant Chemotherapy Effectivity of Adjuvant Chemotherapy in Breast Cancer: Conclusion and in Breast Cancer: Conclusion and

Review of Conflicting Issues.Review of Conflicting Issues.

1. Polychemotherapy significantly reduces the annual risk of relapse and mortality both for N0- as well as N1-breast cancers.

2. Anthracycline-based regimens have been shown to have a significant advantage over non-anthracycline-regimens 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.



Adjuvant Therapy in Breast Cancer: Adjuvant Therapy in Breast Cancer: Final Conclusion.Final Conclusion.

Recruit Patients into Clinical Trials!

Adjuvant Treatment in Breast Cancer

Documents