Prognosis and chemosensitivity using a five monoclonal antibody IHC test in node negative, tamoxifen-treated, ER+ breast cancer - NSABP B14 and B20 trials. Poster at the ASCO 2007 Breast Cancer Symposium

D. T. Ross¹, C. Kim², G. Tang³, O. M. Mejia², R. A. Beck⁴, B. Z. Ring¹, R. S. Seitz⁴, S. Paik², J. P. Costantino⁵, N. Wolmark^6
1Applied Genomics Inc., Burlingame, CA, ²Pathology, NSABP, Pittsburgh, PA, ³Statistics, NSABP and University of Pittsburgh, Pittsburgh, PA, ⁴Applied Genomics Inc, Huntsville, AL, ⁵Graduate School of Public Health, NSABP and University of Pittsburgh, Pittsburgh, PA, ⁶NSABP and Allegheny General Hospital, Pittsburgh, PA.

Abstract

Background: A strong association between disease progression and a novel five antibody IHC test for ER+ breast cancer was previously demonstrated [Ring et al, JCO 2006]. As an additional trial of this IHC test we performed a prospectively designed blinded retrospective study using the combined tamoxifen-treated arms of the NSABP B14 and B20 ER+ N0 trials. We also examined the relationship between treatment with chemotherapy and the IHC test using the tamoxifen plus chemotherapy-treated arm of the B20 trial.

Subjects and Methods: Tissue arrays were constructed in triplicate and stained using five monoclonal antibodies targeting p53, NDRG1, SLC7A5, CEACAM5 and HTF9C. Pre-defined scoring rules and cutpoints for risk strata were applied to the 1007 scored patients (711 in the tamoxifen treated-B14 B20 trials, 296 in the tamoxifen plus chemotherapy treated-B20 trial). RFI was defined as time from entry to any local, regional or distant recurrence.

Results: In a univariate Cox model, the distribution of recurrence events between the test's risk strata for the ten year study period were significantly distinct (HR=1.304, 95%:CI 1.08-1.573, p=0.006). In a multivariate model the test contributed information independent of age, tumor size and menopausal status (p=0.007). Exploratory analysis revealed that the test may have the greatest clinical relevance in patients >60 years old with KM estimates of 10-year proportion of recurrence-free of 78.5% for the high risk group, 89% for the moderate risk group and 92% for the low risk group. The IHC test identified high and low risk groups that both showed significant improvement upon treatment with cytotoxic chemotherapy. However, the formal test for interaction between administration of chemotherapy and the risk group was not significant (p=0.107).

Conclusion: IHC staining patterns using five selected monoclonal antibodies combined using a predefined algorithm assign patients to risk strata significantly associated with outcome in ER+ N0 populations. Exploratory analysis suggests that this test may be most useful in clinical decision making for post-menopausal patients and may be able to identify groups of ER+, node negative patients who have greater absolute benefit from adjuvant chemotherapy compared to unstratified patient populations.

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