Challenging Cases in Cancer: Early Breast Cancer

Clifford A. Hudis, MDChief, Breast Cancer Medicine Service

Attending Physician

Memorial Sloan-Kettering Cancer Center

New York, NY

Case 1

• 57-year old woman with calcifications on her yearly screening mammogram is found to have 1.3 cm of invasive ductal carcinoma

• The tumor is strongly positive for both the estrogen and progesterone receptors and negative for HER2

• After undergoing a lumpectomy with clear margins and a sentinel node procedure yielding negative nodes, she seeks an opinion regarding treatment to improve her overall survival

• She has already planned radiation therapy

Case 1

• Which adjuvant therapy has been shown to offer the greatest impact on overall survival for patients with node-negative, hormone-receptor positive invasive breast cancer?1. Tamoxifen

2. Anastrozole

3. Letrozole

4. Tamoxifen followed by Exemestane

5. Tamoxifen followed by Anastrozole

6. Tamoxifen followed by Letrozole

7. Combination chemotherapy alone

8. Combination chemotherapy AND options 1, 2, 3, 4, 5 or 6

9. Clinical Trial

Case 1

• Which adjuvant therapy has been shown to offer the greatest impact on overall survival for patients with node-negative, hormone-receptor positive invasive breast cancer?1. Tamoxifen

2. Anastrozole

3. Letrozole

4. Tamoxifen followed by Exemestane

5. Tamoxifen followed by Anastrozole

6. Tamoxifen followed by Letrozole

7. Combination chemotherapy alone

8. Combination chemotherapy AND options 1, 2, 3, 4, 5 or 6

9. Clinical trial

Recommended Approach:

• Clinical trial

Effect of Tamoxifen on Breast Cancer Recurrence

Effect of Tamoxifen on Breast Cancer Death

Early Breast Cancer Trialists' Collaborative Group. Lancet. 2005; 365:1687-1717

Selective vs. NonselectiveAromatase Inhibition

Federman, DD: The Adrenal. Dale DC, Federman DD, eds. In: Scientific American Medicine. Section 3. Subsection IV. ©1997 Scientific American Inc. All rights reserved.

Multiple steps involving P-450 enzymes and production of steroid intermediates

Cholesterol

Cortisol AndrostenedioneAldosterone

Testosterone

Estrone Estradiol

Selective Inhibitors

Nonselective Inhibitors

Steroidal and Non-steroidal Aromatase InhibitorsDifferences in Structure and Function

Androstenedione

O

NH2

H

C2H5

ON

Aminoglutethimide

Steroidal Inactivators Androgen Substrate

Non-steroidal Inhibitors

CH3

CH3

CH3

CH3NC CN

AnastrozoleLetrozole

N

O

CH2

O

Exemestane

NC CN

N

NN

O

ONN

Formestane

O

OH

O

* Note that some patients from the original newly diagnosed population are lost due to recurrence or adverse events prior to randomization

TRIALS

• ATAC• BIG 01-98• TEAM

• BIG 01-98

• IES• ITA• ARNO95/ABCSG8*

DIRECT COMPARISON

SWITCHING

*

SEQUENCING

EXTENDED ADJUVANT

• MA.17

Adjuvant AI Hormonal Therapy Trial Designs

All women were:

• Postmenopausal

• 84% HR +

• 61% node -

• 21% Rx chemotx

RecruitmentJuly 1996-March 2000

Anastrozole + Tamoxifen (N=3,125)

Tamoxifen (N=3,116)

Surgery± RT ± chemo

Anastrozole (N=3,125)

5 years

ATAC Design

ATAC: Recurrence (HR +ve)Median follow up 68 months

Patients (%)

Follow-up time (years)

0

5

10

15

20

25

0 1 2 6

Absolute difference: 1.7% 2.4% 2.8% 3.7%

At risk: A 2618 2540 2448 2355 2268 2014 830T 2598 2516 2398 2304 2189 1932 774

Anastrozole (A)

Tamoxifen (T)

3

HR

0.74

0.79

HR +ve

ITT

95% CI

(0.64, 0.87)

(0.70, 0.90)

P-value

0.0002

0.0005

4 5

CI = confidence intervals; HR = hazard ratioITT = intent-to-treat ATAC Trialists’ Group. Lancet 2005;365:60-62

ATAC: Overview of Adverse Events* (%)

*Adverse events on treatment or within 14 days of discontinuation

Drug-related:

AEs

SAEs

AEs leading to withdrawal

P-value

< 0.0001

0.0001

0.0002

Tamoxifen(N=3,094)

68.4

9.0

14.3

Anastrozole(N=3,092)

60.9

4.7

11.1

ATAC Trialists’ Group. Lancet 2005;365:60-62

* Patients 1 fracture occurring before recurrence, including patients no longer on treatment

ATAC: Pre-specified Adverse Events (%)

T

40.9

10.2

13.2

0.8

2.8

4.5

29.4

7.7

5.1

A

35.7

5.4

3.5

0.2

2.0

2.8

35.6

11.0

1.3

Hot flashes

Vaginal bleeding

Vaginal discharge

Endometrial cancer

Ischemic cerebrovascular

Venous thromboembolic

Joint symptoms

Fractures*

Hysterectomy

P-value

< 0.0001

< 0.0001

< 0.0001

0.02

0.03

0.0004

< 0.0001

< 0.0001

< 0.0001

ATAC Trialists’ Group. Lancet 2005;365:60-62

ATAC: Overall SurvivalCurves Shown for HR+ Patients

Includes non breast cancer deaths

At risk:

A 2618 2566 2505 2437 2377 2117 867

T 2598 2549 2502 2430 2333 2080 855

Follow-up time (years)

0

5

10

15

20

25

0 1 2 3 4 5 6

Pa

tient

s (%

)

Anastrozole (A)

Tamoxifen (T)

HR

0.97

0.97

HR+

95% CI

(0.83–1.14)

(0.85-1.12)

P-value

0.7

0.7ITT

A

296

411

T

301

420

ATAC Trialists’ Group. Lancet 2005;365:60-62

BIG 01-98 (FEMTA)

TamoxifenTamoxifen

TamoxifenTamoxifen

LetrozoleLetrozole

LetrozoleLetrozole

LetrozoleLetrozoleRR

AA

NN

DD

OO

MM

II

ZZ

EE

TamoxifenTamoxifen

2 Years2 Years 3 Years3 Years

5 Years5 Years

ER+ and/or ER+ and/or PgR+ PgR+ Postmenopausal Postmenopausal women s/p women s/p surgery surgery ±± chemo, chemo, ±± RT RT

Primary Endpoints: DFS, DDFS, OS

BIG 01-98 Primary Core Analysis

• Compares Letrozole versus Tamoxifen

• Includes all patients

• Letrozole: Arms B and D

• Tamoxifen: Arms A and C

• Excludes events and FU beyond switch for C & D

Tamoxifen

Letrozole

Tamoxifen Letrozole

Letrozole Tamoxifen

A

B

C

D

2-Arm Option

4-Arm Option

TAM

0

20

40

60

80

100

0 1 2 3 4 5

Pe

rce

nt a

live

an

d d

ise

ase

-fre

e

Years from randomization

97.797.6

YearlyDFS (%)

95.193.4

90.589.0

86.884.6

84.081.4

No. at Risk

38923896

29642926

12611238

892866

40034007

567544

LET

N HR (95% CI) P Value

8010 0.81 (0.70-0.93) 0.003

BIG 01-98: Disease-free Survival

Updated Safety Analysis of BIG 01-98 Trial: Cardiovascular Adverse Events During Adjuvant

Letrozole (Let) vs. Tamoxifen (Tam) Therapy

Tamoxifen

Letrozole

Letrozole

BIG 1-98: N = 7963Let - HR: 19% lower for DFS, 27% reduced risk for distant

recurrence compared to Tam.

Grade 3-5 Adverse Event

Number of Events With

Letrozole

(N = 3,975)

Number of Events With Tamoxifen

(N = 3,988)

Relative Risk P

Any CardiacAny Cardiac 9696 5757 1.631.63 .0036.0036

Ischemic Heart DiseaseIschemic Heart Disease 4545 2929 1.461.46 .12.12

HypertensionHypertension 5757 4848 1.181.18 .40.40

CVA/TIACVA/TIA 4747 4747 0.980.98 .94.94

ThromboembolicThromboembolic 3535 9292 0.380.38 < .0001< .0001

Cardiovascular AEs higher for Let, but relatively rare.Patients at risk for thromboembolism should avoid tamoxifen

Coates et al, ASCO 2007, Abstract 521

ABCSG 8 – ARNO 95:Combined Analysis Trial Structure

Primarysurgery+/- RTx

TAM 3 yearsN=1,606

Total patientsN=3,224

ABCSG 8N=2,262

+ARNO 95

N=962

ANA 3 yearsN=1,618

+ TAM 2 years

100% HR positive 74% node negative0% Rx chemotx

Jakesz et al, Lancet 2005;366:455–462

ABCSG 8 – ARNO 95: Event-free Survival 28 Months Median Follow-up

Events = locoregional recurrences, distant metastases, contralateral breast ca

Event-free survival (%)

0

75

80

85

90

95

100

0 1 2 3 4 5

ANA vs TAM P=0.0009 HR 0.60 [95% CI 0.44-0.81]

EFS time in years

ANA

TAM

At risk:

1606 343 176TAMANA 1618

12171243

858874

593623 375 178

ABCSG 8 – ARNO 95: Overall Survival

Number Deaths 3 yrs. OS

(%)

TAM 1,606 59 96.4

ANA 1,618 45 97.1

ANA vs TAM P =0.16 HR 0.76 95% CI 0.52-1.12

Jakesz et al, Lancet 2005;366:455–462

IES Trial Design

Diagnosis

2-3 years2-3 years study

treatment

Total 5 years endocrine therapy

Tamoxifen

RANDOMIZE

Exemestane

5,162*

Tamoxifen

5,294*

Post Treatment Follow-up

10335*

Start of study

* Total women years Coombes et al, ASCO 2006, # LBA527

0

10

20

30

4050

60

70

80

90

100

0 1 2 3 4 5

Time since randomization (years)

% s

urvi

ving

dis

ease

free

0

10

2030

40

50

60

7080

90

100

0 1 2 3 4 5

Time since randomization (years)

% s

urvi

ving

dis

ease

free

IES: Disease-free Survival

yearyear

% abs. diff.% abs. diff.

(95% CI)(95% CI)

2.52.5 55

3.23.2 3.43.4

(1.6 – 4.9)(1.6 – 4.9) (0.1 – 6.8)(0.1 – 6.8)

En

d o

f E

nd

of

trea

tmen

t tr

eatm

ent

ER+/UnknownER+/Unknown

HR = 0.75 (95% CI: 0.65-0.87)HR = 0.75 (95% CI: 0.65-0.87)Log-rank test: Log-rank test: P P = 0.0001= 0.0001

E = 339 / 2296E = 339 / 2296

T = 438 / 2306T = 438 / 2306

E = 354 / 2352E = 354 / 2352

En

d o

f E

nd

of

trea

tmen

ttr

eatm

ent

ITTITT

HR = 0.76 (95% CI: 0.66-0.88)HR = 0.76 (95% CI: 0.66-0.88)Log-rank test: Log-rank test: PP = 0.0001 = 0.0001

T = 454 / 2372T = 454 / 2372

2.52.5 55

3.43.4 3.53.5

(1.8 – 5.1)(1.8 – 5.1) (0.1 – 6.9)(0.1 – 6.9)

Coombes et al, Lancet. 2007 Mar 17;369(9565):906.

0

10

20

30

4050

60

70

80

90

100

0 1 2 3 4 5

Time since randomization (years)

Wom

en a

live

(%)

0

1020

3040

50

6070

8090

100

0 1 2 3 4 5

Time since randomization (years)W

omen

aliv

e (%

)

IES: Overall Survival

yearyear

% abs. diff. % abs. diff.

(95% CI)(95% CI)

2.52.5 55

0.80.8 1.21.2

(-0.4 – 1.9)(-0.4 – 1.9) (-1.5 – 3.9)(-1.5 – 3.9)

En

d o

fE

nd

of

trea

tmen

ttr

eatm

ent

HR = 0.85 (95% CI: 0.71-1.02)HR = 0.85 (95% CI: 0.71-1.02)Log-rank test: Log-rank test: PP = 0.08 = 0.08

E = 222 / 2352E = 222 / 2352

T = 261 / 2372T = 261 / 2372

ITTITT

En

d o

fE

nd

of

trea

tmen

ttr

eatm

ent

HR = 0.83 (95% CI: 0.69-1.00)HR = 0.83 (95% CI: 0.69-1.00)Log-rank test: Log-rank test: P = P = 0.050.05

E = 210 / 2296E = 210 / 2296

T = 251 / 2306T = 251 / 2306

ER+/UnknownER+/Unknown

2.52.5 55

0.70.7 1.61.6

(-0.4 – 1.9)(-0.4 – 1.9) (-1.2 – 4.3)(-1.2 – 4.3)

Coombes et al, Lancet. 2007 Mar 17;369(9565):906.

Primary Endpoint: Disease-free Survival

n = 2,575

n = 2,582

All Postmenopausal Patients and Disease-free

Tamoxifen Placebo

Letrozole

4.5 - 6 years initial adjuvant 5 years extended adjuvant

0 – 3

months

NCIC CTG Intergroup Trial MA.17 Design

Goss PE, et al, NEJM. 349;19 November 6, 2003.

No. at risk (letrozole) 2575 2308 1327 1110 624 9 0

No. at risk (placebo) 2582 2298 1295 610 180 11 0

P P < .001< .001

Letrozole Placebo

0

20

40

60

80

100

Time From Randomization (Months)

0 10 20 30 40 50 60

Per

cent

age

MA.17: Disease-free Survival

Goss PE, et al. J NEJM. 349;19 November 6, 2003.

Adjuvant Endocrine Trials: Efficacy

StrategyStrategy RCTsRCTs PtsPts UpdateUpdate Median FU Median FU (mo.)(mo.) AIAI

Efficacy [HR, Efficacy [HR, PP]]

DFS/EFSDFS/EFS OSOS

Up-FrontUp-FrontATACATAC 6,1866,186 Lancet 2006Lancet 2006 6868 ANAANA 0.87 (0.01)0.87 (0.01) 0.97 (0.7)0.97 (0.7)

BIG-1-98BIG-1-98 4,9224,922 JCO 2007JCO 2007 5151 LETLET 0.82 (0.007)0.82 (0.007) 0.91 (>0.05)0.91 (>0.05)

““Early” Early” SwitchSwitch

ITA-1ITA-1 380380 JCO 2001JCO 2001 6161 AGTAGT NR (0.6)NR (0.6) NR (0.005)NR (0.005)

ITA-2ITA-2 448448 Ann Oncol Ann Oncol 20062006 6464 ANAANA 0.57 (0.005)0.57 (0.005) 0.56 (0.1)0.56 (0.1)

IESIES 4,7424,742 Lancet 2007Lancet 2007 5656 EXEEXE 0.76 (0.0001)0.76 (0.0001) 0.85 (0.08)0.85 (0.08)

ABCSG8/ARNOABCSG8/ARNO 3,2243,224 Lancet 2005Lancet 2005 2828 ANAANA 0.60 (0.0009)0.60 (0.0009) NR (0.16)NR (0.16)

““Extended” Extended” SwitchSwitch

MA.17MA.17 5,1575,157 JNCI 2005JNCI 2005 3030 LETLET 0.58 (0.001)0.58 (0.001) 0.82 (0.3)0.82 (0.3)

ABCSG 6aABCSG 6a 856856 ASCO 2005ASCO 2005 6060 ANAANA 0.64 (0.047)0.64 (0.047) NRNR

NSABP B-33NSABP B-33 1,5981,598 SABCS 2006SABCS 2006 3030 EXEEXE 0.68 (0.07)0.68 (0.07) 1.20 (0.64)1.20 (0.64)

AI’s & Hazard Rate Inflections:Does the Timing of Hormone Therapy Influence

the Change in the RATE of Events?

5 10

YEARS

% DFS

ATAC/BIG 01-98

MA.17

IES/ARNO 8-ABCSG 95

Local/regional

recurrence

Distant metastasis

Deathfrom any

cause

Invasive Contra-lateral breast cancer

Second primary invasive cancer (non-

breast)

Ipsi-lateral DCIS

Contra-lateral DCIS

Ipsi-lateral LCIS

Contra-lateral LCIS

BIG 1-98 X X X X X

MA-17 X X X X X X X

ATAC X X X X X X

IES X X X X

ARNO X X X

NOTE: EFS (Event-free Survival) used by ARNODCIS = Ductal Carcinoma in situLCIS = Lobular Carcinoma in situ

Hudis et al, JCO, Vol 25, No 15 (May 20), 2007: pp. 2127-2132

Example of Inconsistent Definitions of Disease-free Survival

Early Breast Cancer Trialists’ Collaborative Group, Sept 2000 (*Lancet 1998)

Comparison (N)

CMF vs. Nil (12,000)

CMF+ vs. Nil (3,200)

Other vs. Nil (12,000)

*CMF/Tam vs. Tam (640) < 50

*CMF/Tam vs. Tam (9,192) 50+

Anthracyclines+ vs. CMF (13,600)

Longer vs. Shorter (6,100)

Recurrence

+24 ± 3

+20 ± 5

+24 ± 3

+ 21 ± 13

+19 ± 3

+11 ± 3

+6 ± 4

Death

+15 ± 3

+12 ± 5

+16 ±3

+25 ± 14

+ 11 ± 4

+16 ± 3

2 ± 4

PolyChemotherapy:56/64 Available Trials

10,000 Deaths / 28,000 Enrolled

Case 2

• 45-year old woman with calcifications on her yearly screening mammogram is found to have 1.3 cm of invasive ductal carcinoma (infiltrating carcinoma) metastatic to 3 lymph nodes

• She has had a lumpectomy and is planning radiation therapy

• The tumor is weakly positive for both the estrogen and progesterone receptors but also positive by both IHC and FISH for HER2

• She seeks an opinion regarding treatment to prevent recurrence and improve her overall survival

Case 2

• Which adjuvant chemotherapy would you recommend in addition to hormone therapy?

1. CMF x 6 + trastuzumab

2. AC x 4 + trastuzumab

3. FEC/CEF/CAF/FAC + trastuzumab

4. AC x 4 followed by a taxane x 4 + trastuzumab

5. AC x 4 followed by paclitaxel x 4 (all q 2 weeks) + trastuzumab

6. TAC x 6 followed by trastuzumab

7. Carbo/docetaxel + trastuzumab

8. Trastuzumab alone

H Trastuz

DoxorubCyclophPaclitaxDocetaxCBDCA

Adjuvant Trastuzumab

NSABP B-31

NCCTG 9831

H…x 52

H…x 52

H…x 52

H…x 52

H…x 52

BCIRG 006

H…x 1 years

H…x 2 years

No therapy

StandardChemoRx

HERA

B-31/N9831 Survival

ACACTHTH94%94%

91%91%

87%87%

92%92%ACACTT

NN DeathsDeathsACACTT 1,6791,679 9292ACACTHTH 1,6721,672 6262

HR = 0.67, 2P = 0.015HR = 0.67, 2P = 0.015

Years From Randomization

Romond et al, ASCO 2005

Disease-free Survival: Adjuvant Trastuzumab

Romond EH, et al. N Engl J Med. 2005;353:1673-1684.

N9831

Years From Randomization

0 1 2 3 4 5

50

60

70

80

90

100

78%

87%86%

68%

HR: 0.55; 2P = .0005

ACT 807 90ACTH 808 51

0 1 2 3 4 5

50

60

70

80

90

100 B-31

HR: 0.45; 2P = 1x10-9

74%

87%85%

66%

Pat

ien

ts (

%)

N EventsTreatment

872 171864 83

ACTACTH

ACTACTH

Treatment N Events

100

80

60

40

20

0

Patients(%)

Months from randomization

Observation

No. at risk

1703 1627 1498 1190 794 407 146

1698 1606 1424 1042 677 354 126

1-year trastuzumab

59

90

Events HR 95% CI P value

0.63 0.45, 0.87 0.0051

3-yearOS

92.4

89.2

12 360 186 24 30

Smith et al., Proc ASCO 2006

HERA: Overall Survival (censored)Median 2-year FU

Disease-free Survival: 2nd Interim Analysis

Absolute DFS benefitsAbsolute DFS benefits(from years 2 to 4):(from years 2 to 4):

ACACTH vs. ACTH vs. ACT: 6%T: 6%TCH vs. ACTCH vs. ACT: 5%T: 5%

% D

ise

ase

Fre

e

0.5

0.60.6

0.7

0.8

0.9

1.0

0 1 2 3 4 5

PatientsPatients EventsEvents

1,0731,073 192192 ACAC→→TT1,0741,074 128128 ACAC→→THTH1,0751,075 142142 TCHTCH

81%

87%

86%

77%

83%

82%87%

93%

92%

HR (ACHR (AC→→TH vs. ACTH vs. AC→→T) = T) = 0.61 [0.48;0.76]0.61 [0.48;0.76] P P < 0.0001< 0.0001

HR (TCH vs. ACHR (TCH vs. AC→→T) = T) = 0.67 [0.54;0.83]0.67 [0.54;0.83] P P = 0.0003= 0.0003

Year from randomization

Overall Survival: 2nd Interim Analysis

HR (AC→TH vs AC->T) = HR (AC→TH vs AC->T) = 0.59 [0.42;0.85]0.59 [0.42;0.85] P P = 0.004= 0.004HR (TCH vs AC→T) = HR (TCH vs AC→T) = 0.66 [0.47;0.93]0.66 [0.47;0.93] P P = 0.017= 0.017

% S

urvi

val

% S

urvi

val

0.50.5

0.60.6

0.70.7

0.80.8

0.90.9

1.01.0

00 11 22 33 44 55

PatientsPatients EventsEvents1,0731,073 8080 AC→TAC→T1,0741,074 4949 ACAC→→THTH1,0751,075 5656 TCHTCH

97%97%

99%99%

93%93%

97%97%

95%95%92%92%

91%91%

86%86%

Year from randomizationYear from randomization

98%98%

Summary of Results from 5 Adjuvant Trastuzumab Trials

Recurrence Recurrence TrialTrial ControlControl Exp ArmExp Arm Conc ? N=; FU=Conc ? N=; FU= HR, % HR, % MortalityMortality

B31+N9831B31+N983111 AC + PAC AC + PAC Same +Same + YY 3351; 2y 3351; 2y 4747 3333 all Q3W x 4all Q3W x 4 Tras 1y Tras 1y

N9831N9831 AC + PACAC + PAC Same +Same + NN 3585; 1.5y3585; 1.5y 1313 1515 Post CPost C11 all Q3W x 4all Q3W x 4 Tras 1yTras 1y

HERA HERA 22 Any PriorAny Prior Same +Same + NN 3387; 1y3387; 1y 4646 2424 adjuvant CTadjuvant CT Tras 1yTras 1y

BCIRG OO6BCIRG OO633 AC + DAC + D Same +Same + YY 3222; 2y3222; 2y 5151 ------all Q3W X 4all Q3W X 4 Tras 1yTras 1y

CbD +CbD + YY 3222; 2y3222; 2y 3939 ------Tras 1yTras 1y

FinHerFinHer44 D or V + D or V + Same +Same + YY 1010; 3y1010; 3y 5858 5959FEC x 3 FEC x 3 Tras 9W Tras 9W

1.1. Romond EH. N Engl J Med 2005:353:1673-1684Romond EH. N Engl J Med 2005:353:1673-16842.2. Piccart-Gebhart MJ et al. Presented at: ASC0 41Piccart-Gebhart MJ et al. Presented at: ASC0 41stst Annual Meeting; May 13-17, 2005 Annual Meeting; May 13-17, 2005

3.3. Slamon D et al. Presented at: 28Slamon D et al. Presented at: 28thth Annual San Antonio Breast Cancer Symposium; December 8-11, 2005 Annual San Antonio Breast Cancer Symposium; December 8-11, 20054.4. Joensuu H et al, Breast Cancer Res Treat. 2005;94(suppl 1):S5. Abstract 2. Joensuu H et al, Breast Cancer Res Treat. 2005;94(suppl 1):S5. Abstract 2.

CbD = carbloplatin, docetaxel; CT = chemotherapy; D = docetaxel; HR = hazard ratio; Tras = trastuzumab; V = vinorelbineCbD = carbloplatin, docetaxel; CT = chemotherapy; D = docetaxel; HR = hazard ratio; Tras = trastuzumab; V = vinorelbine

q 2 wk (w/G-CSF) q 3 wk

7/481 (1.5%)

5/487 (1%) 12/488 (2.5%)

12/473 (2.5%)*

Grade 3 Post-Rx Cardiac Events:36/1929 (2%)

No association with schedule or regimen( * plus one cardiac death w/Rx)

Hudis et al, SABCS 2005

Trastuzumab is Safe With Dose-Dense: AC→ TPreliminary Results Of MSKCC Pilot: 04-126

N = 70

Dang, et al, SABCS. 2006 (abstr 2101).

HHHHHHHHHH x 52 doses (weeks)

Dose-Dense AC→Paclitaxel (T) + H: Results

Multi-gated radionuclide angiography scan (MUGA) obtained at baseline and at months 2, 6, 9, and 18

MUGA at:

Baseline Month 2 Month 6 Month 9 Month 18

Median LVEF (%) 68 67 66 65 66

Range 55-81 58-79 52-75 53-75 55-75

Dang, et al, SABCS. 2006 (abstr 2101).

LVEF=left ventricular ejection fraction.

CHF in 1 patient of 70

Summary

• Targeting of the estrogen receptor through deprivation of estrogen shows a clear and consistent advantage in post-menopausal women for the use of aromatase inhibitors

• Role of chemotherapy

• Targeted therapies can improve survival in early-stage breast cancer

• Dose-Dense Chemotherapy