Abstract P2-09-14: Evidence for Predictive and Prognostic Impact of Molecular Classification in Taxane-Based Chemotherapy in Intermediate Risk Breast Cancer — An Analysis of the WSG EC-Doc Trial
Authors: Huober J , Gluz O , Hartmann A , Kates R , Kreipe HH , Pelz E , Thomssen C , Fischer HH , Moebus V , Augustin D , Weiss E , Erber R , Liedtke C , Kuhn W , Nitz U , Harbeck N, 
Published: April 2011

Background: Patients with hormone receptor positive breast cancer (BC) and 1-3 positive lymph nodes (LN) belong to the intermediate risk-group. Among these patients chemoendocrine therapy may be considered. The prognostic role of molecular breast cancer subgroups and their predictive impact regarding taxane-and anthracycline based chemotherapy is unclear. This analysis evaluated the ability of molecular subtypes to predict outcome after standard FEC or EC-Doc chemotherapy in pts with 1-3 positive LN.

Methods: The EC-Doc trial randomized 2012 patients with 1-3 positive LN to 6x FEC/CMF vs. 4x EC followed by 4 x docetaxel (Doc). Significantly better DFS and OS in favor of EC-Doc was reported previously (Nitz et al., SABCS 2008). Protein expression data and central histology/grade (G) were available for 772 patients (Control n=390; EC-Doc n=382). Protein expression was measured on tissue micro arrays for ER, PR, Her2 (both IHC/FISH), Ki-67, Ck 5/6, and EGFR. Molecular subgroups were classified using ki-67 cutt-off of 13.25 % (Cheang et al. JNCI 2009). Results: There was no difference in baseline characteristics (age, LN, grade, tumor size, HR) between the entire ITT-study population and the investigated cohort of 772 pts. There were significantly more G 3 tumors in the basal and Her2 group and more G 1/2 tumors in the luminal A cohort. Distribution of molecular subtypes is as follows:

- Luminal A: HR+ (ER and/or PR+), low KI-67 and Her2-: 26.1%

- Luminal B: HR+ and either Ki-67 high or Her2+: 44.8%

- Her2: HR-and Her2+: 10.9%

- Triple negative (TN) basal-like ER/PR/Her2- ; Ck 5/6+ and/or EGFR+: 11.8%

- TN non-basal-like: TNBC; both Ck 5/6 and EGFR-: 6.4%

After median follow up of 64 months, both DFS (5y 90% vs. 80%, p=0.006) and OS (5y 95% vs. 92%, p=0.022) rates also significantly favored EC-Doc vs. FEC in this cohort. DFS rates were highest in luminal A and lowest in TN basal-like tumors.

In univariate analysis a significant benefit of EC-DOC vs. FEC for DFS is seen in luminal B patients (p=0.004; HR=0.41; (0.22-0.77)). EC-Doc was also better than FEC in HR-patients who were not “basal-like (p=.057; HR=0.385 (0.14 — 1.07).

In multivariate analysis including age, nodal status, tumor size, molecular subtypes, and chemotherapy regimen age, luminal A subtype, and interaction of EC-Doc and luminal B subtype (HR=0.44) influenced significantly DFS survival. Conclusions: These data provide evidence that molecular subtypes are associated with both different levels of benefit from EC-Doc and different DFS within each treatment group. These retrospective results will be validated within the prospective WSG PlanB trial.

Table/Figure 1: multivariate model for DFS

Tabid Parameters bssdciated with benefitfrctm EC-Dgccompared to CEF in a multivariate tnofiel tor DFS

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-14.