An Update On Early Breast Cancer: CCO Independent Conference Coverage

An Update on Early Breast
Cancer
CCO Independent Conference Coverage
of the 2011 Annual Meeting of the AACR-CTRC San Antonio
Breast Cancer Symposium*
December 6-10, 2011

San Antonio, Texas
*CCO is an independent medical education company that
provides state-of-the-art medical information to healthcare
professionals through conference coverage and other
educational programs.
This program is supported by educational grants from

An Update on Early Breast Cancer
clinicaloptions.com/oncology
About These Slides

 In the following slides, you will find highlights of the key
studies from this meeting. Be sure to review the slide
notes field for each slide for insightful commentary
from our expert faculty
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Faculty
Joyce O’Shaughnessy, MD
Co-Director, Breast Cancer Research
Baylor Charles A. Sammons Cancer Center
Texas Oncology
US Oncology
Dallas, Texas
Peter Ravdin, MD, PhD
Director of the Breast Cancer Program
The University of Texas Health Science Center at San Antonio
San Antonio, Texas
Disclosures
Joyce O’Shaughnessy, MD, has disclosed that she has
received consulting fees from Biogen Idec, Boehringer
Ingelheim, Bristol-Myers Squibb, Caris Diagnostics, Eisai,
Genentech, GlaxoSmithKline, GTx, Johnson & Johnson,
Roche, and sanofi-aventis and fees for non-CME services
from Bristol-Myers Squibb, Celgene, and sanofi-aventis.
Peter Ravdin, MD, PhD, has disclosed that he has an
ownership interest in Adjuvant, Inc.
Overview of Early Breast Cancer

 Adjuvant Therapy
– TEACH: lapatinib vs placebo
– Bisphosphonate trials
– 7-yr update of ABCSG-12
– 5-yr update of ZO-FAST
– NSABP B-34: clodronate vs placebo
– GAIN: ibandronate vs placebo
 Neoadjuvant Therapy
– GeparTrio Trial : response-guided vs conventional chemotherapy
 Prognosis and Prediction

– DCIS score and risk of recurrence
Adjuvant Therapy
TEACH: Study Design

 Primary endpoint: DFS
 Secondary endpoints: OS, recurrence-free survival, distant recurrence-free
survival
Stratified by time from diagnosis,
lymph node involvement,
hormone receptor status Yr 1
Women with resected Lapatinib 1500 mg once daily

HER2-positive (n = 1571)
stage I-IIIc primary
breast cancer and no
previous trastuzumab
therapy Placebo
(n = 1576)
(N = 3147)
Goss P, et al. SABCS 2011. Abstract S4-7.

TEACH: Risk of Recurrence in Patients

Without Anti-HER2 Therapy
Yr(s) Disease-Free
1.0 Patients, %
0.9
Proportion of Patients
1 99.9
0.8
0.7 2 96.7
With DFS
0.6 3 93.1
0.5 4 91.0
0.4
5 87.8
0.3
0.2 6 84.4
0.1 7 81.1
0 8 79.2
0 1 2 3 4 5 6 7 8 9 10
9 77.2
Yrs
10 74.9
Patients at Risk, n
Placebo 1576 1569 1504 1430 1323 1043 781 539 310 181 96

TEACH: DFS and OS

DFS With Lapatinib vs Placebo Patients, n HR (95% CI) P Value
Overall population 3147 0.83 (0.70-1.00) .053
Time since diagnosis
 < 1 yr 647 0.70 (0.50-0.99)
 ≤ 4 yrs 2248 0.84 (0.69-1.03)
 > 4 yrs 899 0.81 (0.52-1.26)
Hormone receptor status, %
 ER and/or PgR positive 1859 0.98 (0.77-1.25) .886
 ER and PgR negative 1288 0.68 (0.52-0.89) .006
Lymph node involvement
 Positive 1753 0.86 (0.69-1.07)
 Negative 1394 0.78 (0.57-1.07)
 No improvement in OS demonstrated with use of lapatinib:

HR: 0.99 (95% CI: 0.74-1.31; P = .966)
TEACH: DFS in Patients With Centrally

Confirmed HER2+ Disease
Outcome Lapatinib,% Placebo,% DFS HR P
(n = 1230) (n = 1260) (95% CI) Value
0.82
All DFS events 13 17 .04
(0.67-1.00)
 Local 2 3
 Regional 2 2
 Distant 8 11
0.66
 CNS recurrence <1 2 .286
(0.33-1.34)
 Contralateral breast <1 1
 Second primary
2 2
malignancy

TEACH: Safety
 Lapatinib associated with more treatment discontinuation (20%
vs 6%), adjustment/interruption (29% vs 9%) vs placebo
 No difference in incidence of cardiac events between lapatinib
and placebo arms (3% vs 3%)
Adverse Events, % Lapatinib Placebo

(n = 1573) (n = 1574)
Grade 1/2 Grade 3/4 Grade 1/2 Grade 3/4
Diarrhea 55 6 16 1
Rash 54 6 15 1
Nausea 17 1 11 1
Fatigue 15 1 13 1
TEACH: Conclusions
 Adjuvant lapatinib after resection of early HER2+ breast cancer failed
to show significant statistical improvement in DFS, OS vs placebo
– Patients with no previous treatment with trastuzumab
 DFS benefit with lapatinib observed in 2 patient subgroups

– Patients with hormone receptor–negative disease
– Patients receiving lapatinib within 1 yr of primary diagnosis
 HER2 status reassessed by central review

– HER2-positive confirmed by FISH: 79%
– Significant improvement in DFS with lapatinib in this subset of patients
 Most common AEs associated with lapatinib: diarrhea and rash

ABCSG-12: Study Design

 Key endpoints
– Primary: DFS at 5 yrs
– Secondary: relapse-free survival, OS, bone mineral density, safety
1803 premenopausal patients Long-term

TAM 20 mg/day monitoring
with breast cancer, stage I/II
(goserelin 3.6 mg/ 28 days) for 5 yrs
ANA 1 mg/day
Stratified by: for
R
 ER+ and/or PgR+ TAM + ZOL 4 mg q6m recurrence
 Age and
 Stage ANA + ZOL 4 mg q6m survival
 Grade (DFS, OS)
 Lymph nodes
Treatment 3 yrs
(median follow-up: 48 mos)
3-yr 5-yr
BMD BMD
Gnant M, et al. N Engl J Med. 2009;360:679-691.
ABCSG-12 (84 Mos): Efficacy

DFS OS
100 100
80 80
Univariate Multiple Cox Univariate Multiple Cox

60 Regression 60 Regression
DFS (%)
OS (%)
Events, HR P HR P Events, HR P HR P
n (95% CI) Value (95% CI) Value n (95% CI) Value (95% CI) Value
40 40
No 132/903 vs no (Log- vs no No 49/903 vs no (Mantel vs no
ZOL ZOL rank) ZOL ZOL ZOL -Cox) ZOL
20 20
ZOL 98/900 0.72 .014 0.71 .011 ZOL 33/900 0.63 .049 0.61 .033
(0.56-0.94) (0.55-0.92) (0.40-0.99) (0.39-0.96)
0 0
0 12 24 36 48 60 72 84 96 108 0 12 24 36 48 60 72 84 96 108
Mos Since Randomization Mos Since Randomization

Pts at Risk, n Pts at Risk, n
No ZOL 903 858 833 807 758 653 521 405 191
No ZOL903 864 856 839 811 706 576 456 215
ZOL 900 862 841 822 788 674 544 419 208
ZOL 900 868 858 849 818 708 587 454 232
Gnant M, et al. SABCS 2011. Abstract S1-2

ABCSG-12 (84 Mos): First DFS Events

Death without
140 3 previous recurrence
120 18 Secondary
malignancy
First Event/Patient (n)
13
100 Contralateral
14
breast cancer
80 11
65 Distant
60 recurrence
56 Locoregional
40
recurrence
20 36
19
0
No ZOL ZOL
(n = 903) (n = 900)
Gnant M, et al. SABCS 2011. Abstract S1-2

ABCSG-12 (84 Mos): Age Effect on DFS

40 Yrs of Age or Younger Older Than 40 Yrs of Age
100 100
80 80
60 60
DFS (%)
40 Univariate 40 Univariate
Events, n HR (95% CI) P Value Events, n HR (95% CI) P Value
20 No ZOL 42/213 vs no ZOL (Log-rank) 20 No ZOL 90/690 vs no ZOL (Log-rank)

ZOL 35/200 0.87 (0.55-1.36) .525 ZOL 63/700 0.66 (0.48-0.92) .013
0 0
0 12 24 36 48 60 72 84 96 108 0 12 24 36 48 60 72 84 96 108
Mos Since Randomization Mos Since Randomization
Pts at Risk, n Pts at Risk, n
No ZOL 213 202 194 189 177 157 127 102 52 No ZOL 690 656 639 616 581 496 394 303 139
ZOL 200 192 185 180 169 148 125 94 48 ZOL 700 670 656 642 619 526 419 325 160
Gnant M, et al. SABCS 2011. Abstract S1-2.

ABCSG-12: Conclusions
 Survival benefits with addition of ZOL to endocrine therapy
first reported at median follow-up of 48 mos are still
present at 84 months
– Significant improvement in DFS
– Relative risk reduction: 28%
– Significant improvement in OS
– Relative risk reduction: 37%
 Subanalysis suggests that survival benefits of ZOL may be

restricted to patients older than 40 yrs of age
Gnant M, et al. SABCS 2011. Abstract S1-2.

ZO-FAST: 5-Yr Final Analysis

Treatment duration 5 yrs
Letrozole +
Stage I-IIIa breast cancer Zoledronic Acid 4 mg
 Postmenopausal or q6m
amenorrheic due to
cancer treatment
 ER+ and/or PgR+
 T-score ≥ -2 SD Letrozole + Delayed*
 N = 1065 Zoledronic Acid 4 mg
q6m
*If 1 of the following occurs:

BMD T score < -2 SD
Clinical fracture
Asymptomatic fracture at 36 mos
De Boer R, et al. SABCS 2011. Abstract S1-3.

ZO-FAST (Primary Endpoint): Median

Change in Lumbar Spine BMD
6 Immediate ZOL P < .0001 for each
Delayed ZOL
Change in LS (LS-L4) BMD (%)
4 264
339 313 290
2 360
Δ 5.9% Δ 8.2% Δ 8.8% Δ 9.2% Δ 10.0%
0
-2
369
-4 343 311 294 264
-6 12 mos 24 mos 36 mos 48 mos 60 mos
ZO-FAST: Final 5-Yr DFS

100 100
90 90
80 80
ITT Population Censored Analysis*
70 70
DFS (%)
DFS (%)
60 60
50 50
40 HR: 0.66; log-rank P = .0375 40 HR: 0.62; log-rank P = .024
30 30
20 IM-ZOL 4 mg (42 events) IM-ZOL 4 mg (42 events)
D-ZOL 4 mg (62 events) 20 D-ZOL 4 mg (53 events)
10 10
0 0
0
6 12 18 24 30 36 42 48 54 60 66 0 6 12 18 24 30 36 42 48 54 60 66
Pts at Risk, n Time on Study (Mos) Pts at Risk, n Time on Study (Mos)
IM-ZOL 532 518 500 488 475 376 IM-ZOL 532 518 500 488 475 376
D-ZOL 533 511 491 475 463 368 D-ZOL 533 459 402 376 350 267
*Censored patients at initiation of delayed ZOL (n = 144).

ZO-FAST: Disease Recurrence

Disease Recurrence Key Sites of Distant
Recurrence*
70 70
Distant Liver
60 Contralateral 60 Lung
Local Lymph node
50 50 9
Patients (n)
Patients (n)
Bone
40 41 40 11
30 30 11 9
29 9
20 20
6 5
10 10 24
12 3 14
0 5 0
D-ZOL IM-ZOL D-ZOL IM-ZOL
(n = 533) (n = 532) (n = 533) (n = 532)
*Multiple sites may be recorded within the same patient.
ZO-FAST: Overall Survival (ITT

Population)
100
90
80
70
60
OS (%)
50
40 HR: 0.69; log-rank P = .196
30
IM-ZOL 4 mg (26 events)
20 D-ZOL 4 mg (36 events)
10
0
0 6 12 18 24 30 36 42 48 54 60 66
Pts at Risk, n Time on Study (Mos)
IM-ZOL 532 522 511 502 485 406
D-ZOL 533 519 505 491 480 407
ZO-FAST: Conclusions
 Immediate initiation of ZOL at start of letrozole significantly
prolonged DFS vs delayed initiation of ZOL in
postmenopausal women with endocrine-responsive EBC[1]
– Continued to improve BMD after 5 yrs of follow-up
– 34% improvement in DFS
 Findings consistent with those observed in ABCSG-12 and
subset of patients > 5 yrs postmenopause in AZURE[2,3]
1. De Boer R, et al. SABCS 2011. Abstract S1-3. 2. Coleman RE, et al. N Engl J Med. 2011;365:1396-
1405. 3. Gnant M, et al. SABCS 2011. Abstract S1-2.
Zoledronic Acid Studies: DFS Comparison

0.66 P Value
ZO-FAST[1] N = 1065 .0375
 104 events
0.75
AZURE: > 5 yrs postmenopausal[2] n = 1041 .02
 263 events
0.71
ABCSG-12[3]
N = 1803 .011
 230 events
0.2 0.4 0.6 0.8 1.0 1.2 1.4

HR
1. De Boer R, et al. SABCS 2011. Abstract S1-3. 2. Coleman RE, et al. N Engl J Med. 2011;365:1396-
1405. 3. Gnant M, et al. SABCS 2011. Abstract S1-2.
NSABP B-34: Phase III Study of Adjuvant

Clodronate in Breast Cancer
 Primary endpoint: DFS (mean follow-up: 8.4 yrs)
 Two thirds aged 50 yrs or older; 25% node positive
Stratified by age, number of positive 3 Yrs
nodes, and ER/PgR status
Clodronate 1600 mg/day*

(n = 1662)
Women with stage I-III
breast cancer
(N = 3323) Placebo*
(n = 1661)
*All patients could receive adjuvant systemic chemotherapy with or without tamoxifen or no adjuvant
therapy at investigator discretion.
Paterson A, et al. SABCS 2011. Abstract S2-3.
NSABP B-34: Analysis of Specified

Endpoints
Endpoint Events, n HR (95% CI) P Value
Clodronate Placebo
(n = 1655) (n = 1656)
DFS 286 312 0.913 (0.778-1.072) .266
OS 140 167 0.842 (0.672-1.054) .131
RFI 148 177 0.834 (0.671-1.038) .101
BMFI 61 80 0.765 (0.548-1.068) .114
NBMFI 78 105 0.743 (0.554-0.996) .046

NSABP B-34 Subset Analysis: DMFI, RFI,

BMFI, NBMFI in Pts Aged > 50 Yrs
Endpoint for Patients Aged HR P Value
50 Yrs or Older
DMFI 0.62 .003
RFI 0.76 .05
BMFI 0.61 .024
NBMFI 0.63 .015

NSABP B-34: Conclusions

 No significant benefit in DFS (primary endpoint) with oral
clodronate in women with early breast cancer[1]
 Clodronate significantly reduced NBMFI vs placebo[1]
– HR: 0.743; 95% CI: 0.554-0.996; P = .046
 In patients aged 50 yrs or older, clodronate associated with

significant improvements in RFI, BMFI, NBMFI vs placebo[1]
– Findings consistent with those observed in older, postmenopausal
women in other adjuvant bisphosphonate studies[2-4]
 Adverse events similar in clodronate and placebo arms[1]
1. Paterson A, et al. SABCS 2011. Abstract S2-3. 2. De Boer R, et al. SABCS 2011. Abstract S1-3.
3. Coleman RE, et al. N Engl J Med. 2011;365:1396-1405. 4. Gnant M, et al. SABCS 2011. Abstract S1-2.
German GAIN Trial: Study Design

Randomized 2:1* Yr 2
Ibandronate 50 mg/day PO
Patients aged 65 yrs or (n = 2015)
younger with previously
untreated node-positive
primary breast cancer
Observation
(N = 3023) (n = 1008)
*Patients in trial also randomized 1:1 to receive ETC vs epirubicin/cyclophosphamide followed by paclitaxel/capecitabine
(EC-TX).
ECT regimen: epirubicin 150 mg/m2 every 2 wks for 3 cycles, followed by paclitaxel 225 mg/m 2 every 2 wks for 3 cycles,
followed by cyclophosphamide 2000 mg/m 2 every 2 wks for 3 cycles.
EC-TX regimen: concurrent epirubicin 112.5 mg/m 2 and cyclophosphamide 600 mg/m 2 every 2 wks for 4 cycles, followed
by concurrent paclitaxel 67.5 mg/m 2 wkly for 10 wks and capecitabine 2000 mg/m 2 on Days 1-14 every 3 wks for 4 cycles.
During chemotherapy, all patients received primary prophylaxis with pegfilgrastim and either epoetin or darbepoetin.
Mobus V, et al. SABCS 2011. Abstract S2-4.

GAIN: Patient Characteristics

Characteristic Ibandronate Observation
(n = 1996) (n = 998)
Age, median yrs 49 50
Premenopausal, % 48.4 47.2
pT4, % 2.1 1.4
pN1, % 38.1 37.1
pN2, % 34.9 36.3
pN3, % 27.0 26.7
Mastectomy, % 44.5 43.3
Ductal invasive, % 77.4 77.1
Grade 3, % 47.3 44.3
Hormone receptor positive, % 76.5 77.7
HER2 positive, % 22.1 21.8

GAIN: DFS and OS (ITT)

Product-Limit Survival Estimates Product-Limit Survival Estimates
With Number of Subjects at Risk With Number of Subjects at Risk
1.0 1.0 + Censored
+ Censored
0.8 0.8
Survival Probability
0.6 0.6
3-yr DFS: 3-yr OS:
Ibandronate 87.6% Ibandronate 94.7%
0.4 Observation: 87.2% 0.4 Observation: 94.1%
Cox regression: Cox regression:
0.2 HR: 0.945 (95% CI: 0.768-1.16; P = .59) 0.2 HR: 1.04 (95% CI: 0.763-1.42; P = .80)
0 Pts at risk, n 0 Pts at risk, n

1996 1814 1590 1057 555 210 1996 1836 1653 1121 586 219
998 871 727 483 264 105 998 886 756 506 277 112
0 12 24 36 48 60 0 12 24 36 48 60
DFS (Mos) OS (Mos)
Ibandronate Observation
GAIN: Subgroup Analyses

DFS for Ibandronate in Subgroups
pN1 HR: 1.04 (95% CI: 0.652-1.65; P = .877)

pN2 HR: 0.875 (95% CI: 0.599-1.28; P = .490)
pN3 HR: 0.951 (95% CI: 0.710-1.27; P = .734)
ER and/or PgR positive HR: 0.952 (95% CI: 0.736-1.23; P = .706)
ER and PgR negative HR: 0.856 (95% CI: 0.604-1.21; P = .383)
Pre- and perimenopausal HR: 1.02 (95% CI: 0.756-1.37; P = .912)
Postmenopausal HR: 0.897 (95% CI: 0.671-1.20; P = .462)
< 60 yrs HR: 1.02 (95% CI: 0.807-1.30; P = .842)
≥ 60 yrs HR: 0.746 (95% CI: 0.490-1.14; P = .172)
0.5 1.0 1.5

HR
Better with ibandronate Worse with ibandronate
GAIN: Conclusions
 Adjuvant ibandronate did not improve DFS nor OS
following dose-dense chemotherapy in patients with node-
positive primary breast cancer
 GAIN trial still ongoing to compare the 2 different dose-
dense chemotherapy regimens

Ongoing Phase III Trials of Antitumor

Properties of Bone-Targeted Agents
Trial Regimen Primary Outcomes
SWOG 0307 ZOL vs clodronate vs ibandronate DFS, OS
NATAN ZOL after neoadjuvant chemo EFS
Dmab 120 mg/mo for 6 mos, then Bone metastasis–free
D-CARE
120 mg q3m vs placebo survival
Triptorelin + tamoxifen vs
HOBOE triptorelin + letrozole vs DFS
triptorelin + letrozole + ZOL
FEC-D vs FEC-DG →
SUCCESS DFS
2 yrs ZOL vs 5 yrs ZOL
ABCSG-18 Dmab 60 mg q6m vs placebo Time to first fracture
Neoadjuvant Therapy
GeparTrio Trial: Study Design

TAC-NX*
(4 cycles NX)
(n = 301)
Not working? Minimal
Try another type response‡
of chemotherapy (n = 622)
TAC x 6
(4 additional cycles TAC)
(n = 321)
Women with
operable or locally
advanced TAC* Assess
breast cancer (2 cycles) response† TAC x 6
(4 additional cycles TAC)
(N = 2072) (n = 704)
*TAC regimen: docetaxel 75 mg/m2, doxorubicin 50
mg/m2, cyclophosphamide 500 mg/m 2 all on Day 1 q21d. CR or PR
NX regimen: vinorelbine 25 mg/m2 on Days 1 and 8, (n = 1390)
capecitabine 1000 mg/m2 on Days 1-14 q21d. TAC x 8
†
Response assessed by ultrasound/palpation. (6 additional cycles TAC)
‡
< 50% tumor reduction. Working? (n = 686)
Give more of the same
chemotherapy
Von Minckwitz G, et al. SABCS 2011. Abstract S3-2.
GeparTrio Trial: DFS and OS

 Median follow-up: 62 mos
Endpoint HR for Response-Guided vs P Value
Conventional Chemotherapy (95% CI)
DFS 0.71 (0.60-0.85) < .001
OS 0.79 (0.63-0.99) .048
 DFS benefit in early responding and nonresponding patients who

received response-guided vs conventional chemotherapy
Patient Treatment HR for DFS P Value
Subgroup Comparison (95% CI)
Responders TAC x 8 vs TAC x 6 0.78 (0.62-0.97) .026
Nonresponders TAC-NX vs TAC x 6 0.59 (0.49-0.82) .001

GeparTrio Trial: DFS by Patient Subgroup

Test for
Subgroup N patients HR (95% CI) Interaction
Overall 2012 0.74 (0.60-0.85)
Age (yrs)
<40 353 0.66 (0.42-1.03) 0.67
≥ 40 1659 0.73 (0.60-0.88)
cT-stage
cT1-3 1737 0.70 (0.56-0.85) 0.66
cT4 267 0.79 (0.54-1.17)
cT-size
< 40 mm 775 0.62 (0.44-0.85) 0.22
≥ 40 mm 1212 0.79 (0.63-0.98)
cN status
Negative 894 0.84 (0.61-1.14) 0.19
Positive NR 0.66 (0.53-0.82)
Histological type
Ductal or other 1571 0.73 (0.60-0.88) 0.71
Lobular 270 0.61 (0.37-1.03)
Grade
1 or 2 1176 0.79 (0.61-1.01) 0.25
3 725 0.65 (0.49-0.85)
Hormone receptor status
Negative 717 0.94 (0.73-1.22) 0.008
Positive 1295 0.56 (0.44-0.73)
HER2 status
Negative 1145 0.63 (0.49-0.81) 0.54
Positive 486 0.72 (0.51-1.04)
Breast cancer phenotype
Luminal A 572 0.55 (0.37-0.82) 0.12-0.01
Luminal B (HER2-) 211 0.40 (0.20-0.79)
Luminal B (HER2+) 281 0.56 (0.33-0.96)
HER2+ (nonluminal) 178 1.01 (0.61-1.67)
Triple negative 362 0.87 (0.61-1.25)
0.2 0.4 0.6 0.8 1.0 1.2 1.4
Response-guided treatments better Conventional treatments better
GeparTrio Trial: pCR by Breast Cancer

Subtype
40
35
30
25
pCR (%)
20
15
10
0
Luminal A Luminal B Luminal B HER2+ Triple Negative
(n = 572) (HER2-) (HER2+) (Nonluminal) (n = 362)
(n = 211) (n = 281) (n = 178)
GeparTrio Trial: Conclusions

 Adapting neoadjuvant chemotherapy based on early
response significantly improved DFS and OS vs
conventional chemotherapy
 Response-guided chemotherapy most effective in patients
with luminal A or luminal B tumors
– Low pCR rates in these tumors
– pCR not prognostic
 No DFS benefit with response-guided chemotherapy in
patients with HER2-positive or triple-negative tumors

Prognosis and Prediction
DCIS Score: Determining Risk of

Recurrence After DCIS Resection
 DCIS Score: gene-based score designed to predict for local
recurrence[1]
– Developed using subset of genes prognostic in both tamoxifen-
treated and tamoxifen-untreated patients
– Proliferation group: Ki67, STK15, survivin, CCNB1 (cyclin B1), MYBL2
– Hormone receptor group: PgR
– GSTM1
– Reference group: ACTB (β-actin), GAPDH, RPLPO, GUS, TFRC
 Evaluated using samples and data from ECOG E5194 trial[2]
1. Solin LJ, et al. SABCS 2011. Abstract S4-6. 2. Hughes LL, et al. J Clin Oncol. 2009;27:5319-5324.
DCIS Score: Patient Characteristics

(N = 327)
 Median age: 61 yrs
 Postmenopausal: 76%
 Median tumor size: 7 mm
– Tumor size ≤ 10 mm: 80%
 Negative margins ≥ 5 mm: 65%
 ER positive: 97%
 Treated with tamoxifen: 29%
 E5194 cohort 1 (low-/intermediate-grade DCIS, size
≤ 2.5 cm): 83%
 E5194 cohort 2 (high-grade DCIS, size ≤ 1 cm): 17%
Solin LJ, et al. SABCS 2011. Abstract S4-6.
DCIS Score: Risk of Ipsilateral Breast

Events (IBE)
Factor HR (95% CI) P Value
DCIS Score 2.34 (1.15-4.59) .02
21-gene RS 0.70 (0.15-2.65) .62
Tamoxifen use 0.56 (0.24-1.15) .12
10-Yr IBE by Risk Group
DCIS Score n 10-Yr Risk, % (95% CI) DCIS Score n 10-Yr Risk, % (95% CI)
50 Group 50 Group
45 High 36 27.3 (15.2-45.9) 45 High 36 19.1 (9.0-37.7)
Intermediate 45 24.5 (13.8-41.1) 40 Intermediate 45 8.9 (2.9-25.8)
40 Low 246 5.1 (2.8-9.5)
Low 246 12.0 (8.1-17.6)
35 35
30 Log-rank P = .02
30 Log-rank P = .01
25 25
20 20
15 15
10 10
5 5
0 0
0 2 4 6 8 10 0 2 4 6 8 10
Yrs Yrs
DCIS Score: Conclusions

 DCIS Score predicts 10-yr risk of IBE in patients with DCIS
treated with surgery in the absence of radiation therapy
– Not affected by adjuvant tamoxifen
– Independent prognostic information on IBE risk provided
above that attained with clinical and pathologic variables

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An Update on Early Breast

December 6-10, 2011

This program is supported by educational grants from

About These Slides

Overview of Early Breast Cancer

– 5-yr update of ZO-FAST

– NSABP B-34: clodronate vs placebo

– GAIN: ibandronate vs placebo

 Prognosis and Prediction

TEACH: Study Design

Women with resected Lapatinib 1500 mg once daily

Goss P, et al. SABCS 2011. Abstract S4-7.

TEACH: Risk of Recurrence in Patients

Goss P, et al. SABCS 2011. Abstract S4-7.

TEACH: DFS and OS

 No improvement in OS demonstrated with use of lapatinib:

TEACH: DFS in Patients With Centrally

Goss P, et al. SABCS 2011. Abstract S4-7.

Adverse Events, % Lapatinib Placebo

 DFS benefit with lapatinib observed in 2 patient subgroups

– Patients receiving lapatinib within 1 yr of primary diagnosis

 HER2 status reassessed by central review

– Significant improvement in DFS with lapatinib in this subset of patients

 Most common AEs associated with lapatinib: diarrhea and rash

ABCSG-12: Study Design

1803 premenopausal patients Long-term

ABCSG-12 (84 Mos): Efficacy

Univariate Multiple Cox Univariate Multiple Cox

Mos Since Randomization Mos Since Randomization

Gnant M, et al. SABCS 2011. Abstract S1-2

ABCSG-12 (84 Mos): First DFS Events

Gnant M, et al. SABCS 2011. Abstract S1-2

ABCSG-12 (84 Mos): Age Effect on DFS

20 No ZOL 42/213 vs no ZOL (Log-rank) 20 No ZOL 90/690 vs no ZOL (Log-rank)

Gnant M, et al. SABCS 2011. Abstract S1-2.

 Subanalysis suggests that survival benefits of ZOL may be

Gnant M, et al. SABCS 2011. Abstract S1-2.

ZO-FAST: 5-Yr Final Analysis

*If 1 of the following occurs:

De Boer R, et al. SABCS 2011. Abstract S1-3.

ZO-FAST (Primary Endpoint): Median

ZO-FAST: Final 5-Yr DFS

De Boer R, et al. SABCS 2011. Abstract S1-3.

ZO-FAST: Disease Recurrence

ZO-FAST: Overall Survival (ITT

Zoledronic Acid Studies: DFS Comparison

0.2 0.4 0.6 0.8 1.0 1.2 1.4

NSABP B-34: Phase III Study of Adjuvant

Clodronate 1600 mg/day*

NSABP B-34: Analysis of Specified

Paterson A, et al. SABCS 2011. Abstract S2-3.

NSABP B-34 Subset Analysis: DMFI, RFI,

Paterson A, et al. SABCS 2011. Abstract S2-3.

NSABP B-34: Conclusions

 In patients aged 50 yrs or older, clodronate associated with

German GAIN Trial: Study Design

Mobus V, et al. SABCS 2011. Abstract S2-4.

GAIN: Patient Characteristics

Mobus V, et al. SABCS 2011. Abstract S2-4.

GAIN: DFS and OS (ITT)

0 Pts at risk, n 0 Pts at risk, n

GAIN: Subgroup Analyses