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The 70-Gene Profile and
Chemotherapy Benefit in 1,600
Breast Cancer Patients
Bender RA et al.
ASCO 2009; Abstract 512. (Oral Presentation)
Introduction


Gene expression profiling has enabled assignment of risk profiles for
patients with early-stage breast cancer (BC) not easily achieved using
clinicopathologic variables
70-gene signature predicts 10-yr distant metastases-free survival (DMFS)
[J Natl Cancer Inst 2006;98(17):1183]
– Low risk: 90%; High risk 71%

70-gene signature predicts pathologic complete response to neoadjuvant
chemotherapy (Breast Cancer Res Treat 2009 Feb 13 Epub ahead of print)
– Low risk: 0%; High risk: 20%

Current study objectives:
– Pooled meta-analysis including patients from 7 large data sets at
multiple institutions across Europe (N = 1,696)
– Analyzed 541 patients with 0-3 involved lymph nodes who received
endocrine therapy (ET) or ET plus chemotherapy (ET + CT)
Source: Bender RA et al. ASCO 2009; Abstract 512.
Patients Treated with
Adjuvant ET or ET + CT
No. of
Patients
(n = 1,696)
0-3 Lymph
Nodes Involved
(n = 541)*
Van de Vijver 2002
295
30
Buyse 2006
302
0
Bueno-de-Mesquita 2007
427
182
Bueno-de-Mesquita 2008
123
29
Mook 2008a
241
154
Mook 2008b
148
27
Kok 2009
160
119
7 Clinical Studies in the Meta-Analysis
*Abstract included 575 patients, including all lymph node positive disease;
here patients with >3 nodes excluded
Source: Bender RA. ASCO 2009; Abstract 512.
Distant Disease-Free Survival (DDFS)
of Treated Patients as a Function of
70-Gene Risk Profile (MammaPrint)
100
95%
82%
80
Low risk (n=252, 47%)
High risk (n=289, 53%)
60
Percent
Survival
40
HR 3.88 (1.99-7.58)
P<0.01
20
0
0
1
2
3
4
5
Time in years
Source: With permission from Bender RA. ASCO 2009; Abstract 512.
DDFS in Patients Receiving
ET vs ET + CT
MammaPrint Low Risk (n = 252)
100
99%
93%
80
ET (n=174, 69%)
ET+CT (n=78, 31%)
60
Percent
Survival
40
HR 0.26 (0.03-2.02)
P=0.20
20
0
0
1
2
3
4
5
Time in years
Source: With permission from Bender RA. ASCO 2009; Abstract 512.
DDFS in Patients Receiving
ET vs ET + CT
MammaPrint High Risk (n = 289)
100
88%
80
76%
ET (n=141, 49%)
ET+CT (n=148, 51%)
60
Percent
Survival
40
HR 0.35 (0.17-0.71)
P<0.01
20
0
0
1
2
3
4
5
Time in years
Source: With permission from Bender RA. ASCO 2009; Abstract 512.
Summary and Conclusions

Patients with a “low risk” 70-gene profile are at sufficiently low
risk of developing distant metastases that adjuvant CT appears
to add no benefit to ET alone

Patients with a “high risk” profile are at high risk of developing
distant metastases and are likely to benefit from the addition of
CT to ET

MINDACT, the ongoing prospective randomized clinical trial in
Europe, is assessing the benefit of treatment assignment, based
on gene expression profiling instead of conventional
clinicopathologic risk assessment
Source: Bender RA et al. ASCO 2009; Abstract 512.
MINDACT: Comparison of 70-Gene Signature with
Clinical Assessment in Selecting Patients with
Node-Negative Breast Cancer for Adjuvant Chemotherapy
Eligibility: T1, T2 or operable T3 invasive breast cancer; 0-3 positive nodes; unilateral tumor
Target accrual: 6,000
Chemotherapy
Clinical high risk,
genomic high risk
Evaluate for
clinical-pathological
risk (using
Adjuvant! Online)
AND 70-gene
signature risk
(using
MammaPrint®)
Discordant
risk between
standard clinicalpathological and
70-gene signature
criteria
R
Clinical low risk,
genomic low risk
Use clinicalpathological risk
results to determine
chemotherapy
or not
Use 70-gene risk
results to determine
chemotherapy
or not
No chemotherapy
Source: Cardoso F et al. J Clin Oncol 2008;26(5):729-735.