Comparison of EndoPredict and EPclin With Oncotype DX Recurrence Score for Prediction of Risk of Distant Recurrence After Endocrine Therapy
Received: December
Comparison of EndoPredict and EPclin With Oncotype DX Recurrence Score for Prediction of Risk of Distant Recurrence After Endocrine Therapy
Richard Buus 0
Ivana Sestak 0
Ralf Kronenwett 0
Carsten Denkert 0
Peter Dubsky 0
Kristin Krappmann 0
Marsel Scheer 0
Christoph Petry 0
Jack Cuzick 0
Mitch Dowsett 0
0 Affiliations of authors: The Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research , London, UK (RB , MD); Academic Department of Biochemistry, Royal Marsden Hospital , London, UK (RB , MD); Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London , London , UK ( IS, JC); Sividon Diagnostics GmbH , Cologne, Germany (RK, KK, MS , CP); Institute of Pathology, Charite ́ University Hospital and German Cancer Consortium (DKTK) , Berlin , Germany ( CD); Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna , Vienna , Austria ( PD) Royal Marsden Hospital , Fulham Road, London, SW3 6JJ , UK
Background: Estimating distant recurrence (DR) risk among women with estrogen receptor-positive (ERþ), human epidermal growth factor receptor 2 (HER2)-negative early breast cancer helps decisions on using adjuvant chemotherapy. The 21-gene Oncotype DX recurrence score (RS) is widely used for this. EndoPredict (EPclin) is an alternative test combining prognostic information from an eight-gene signature (EP score) with tumor size and nodal status. We compared the prognostic information provided by RS and EPclin for 10-year DR risk. Methods: We used likelihood ratio v2 and Kaplan-Meier survival analyses to compare prognostic information provided by EP, EPclin, RS, and the clinical treatment score (CTS) of clinicopathologic parameters in 928 patients with ERþ disease treated with five years' anastrozole or tamoxifen. Comparisons were made for early (0-5 years) and late (5-10 years) DR according to nodal status. All statistical tests were two-sided. Results: In the overall population, EP and EPclin provided substantially more prognostic information than RS (LRv2: EP ¼ 49.3; LRv2: EPclin ¼ 139.3; LRv2: RS ¼ 29.1), with greater differences in late DR and in node-positive patients. EP and EPclin remained statistically significantly prognostic when adjusted for RS (DLRv2: EPþRS vs RS ¼ 20.2; DLRv2: EPclinþRS vs RS ¼ 113.8). Using predefined cut-offs, EPclin and RS identified 58.8% and 61.7% patients as low risk, with hazard ratios for non-low vs low risk of 5.99 (95% confidence interval [CI] ¼ 3.94 to 9.11) and 2.73 (95% CI ¼ 1.91 to 3.89), respectively. Conclusions: EP and EPclin were highly prognostic for DR in endocrine-treated patients with ERþ, HER2-negative disease. EPclin provided more prognostic information than RS. This was partly but not entirely because of EPclin integrating molecular data with nodal status and tumor size.
-
Breast cancer is the most common cancer in women. About
80% of primary breast cancers are estrogen receptor (ER)–
positive disease. Patients with ER-positive disease receive
adjuvant endocrine therapy after surgery that markedly
improves their prognosis (
1
). A large proportion of patients
receiving endocrine therapy have sufficiently low risk to
safely avoid chemotherapy. Differentiating these patients
from higher-risk patients who may benefit from
adjuvant chemotherapy is a priority for breast cancer
management (
2
).
1 of 7
E
L
C
I
T
R
A
Multigene expression prognostic assays may be used to
estimate residual risk of recurrence following surgery and endocrine
treatment to aid decisions on the appropriateness of
chemotherapy treatment. The most widely used test is the Oncotype DX
21gene recurrence score (RS) (
3
). Other prognostic scores to
estimate residual risk in endocrine-treated patients include the
PAM50 risk of recurrence (ROR) score (
4
), the Breast Cancer Index
(BCI) (
5
), and the IHC4 test that is immunohistochemically based
and is combined with the clinical treatment score (CTS) to
integrate clinicopathological parameters (
6
). The amount of
prognostic information provided for early (0-5 years) and late (beyond
five years) recurrence varies across these tests (
7
).
The EndoPredict (EP) assay combines the expression of three
proliferative and five ER-signaling/differentiation-associated
genes and is normalized by three housekeeping genes (
8
). EP
may be measured in formalin-fixed, paraffin-embedded tissue
sections by quantitative real-time polymerase chain reaction
(qRT-PCR) in decentralized laboratories (
9
) and provides a score
that ranges between 0 and 15 after scaling. EPclin was derived
from EP by incorporating nodal status and tumor size to create
an integrated diagnostic algorithm for clinical decisions (
8
).
Both EP and EPclin were trained on a cohort of 964 patients with
ER-positive, human epidermal growth factor receptor 2 (HER2)–
negative carcinomas treated with adjuvant endocrine therapy
only (
8
). Thresholds for EP and EPclin t (...truncated)