Abstract P5-08-50: Associations of MYC protein expression and gene status with breast cancer subtypes and outcome in patients treated with anthracycline-based adjuvant chemotherapy

Abstract

Abstract Background-Aim: Breast cancer is a heterogeneous disease and despite recent scientific progress there is still need for the identification of biomarkers associated with risk for relapse, as well as for markers identifying patients who will benefit from specific treatments. The aim of the present study was to investigate the role of MYC, as a clinically meaningful biomarker, in the outcome of breast cancer subtypes. Patients and Methods: We have pooled the patients and the respective breast carcinomas from two randomized anthracycline-based adjuvant phase III trials, consecutively conducted by the Hellenic Cooperative Oncology Group (HE10/97 and HE10/00). The HE10/97 trial included a non-paclitaxel arm. Tissue microarrays were constructed from 1,060 formalin-fixed paraffin-embedded tumor tissue samples that were collected retrospectively in the first and prospectively in the second trial. MYC was evaluated by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in 986 cases. Results: In total 61.0% of the cases showed positive cytoplasmic MYC immunostaining, while 26.5% showed positive nuclear staining. 65-80% of the patients were characterized as non-amplified or loss/normal-low gain in all FISH cut-offs examined. A weak association was observed between FISH and nuclear protein expression of MYC. High histological grade was associated with MYC protein overexpression and gene amplification. In terms of disease-free survival (DFS), low (2.5-5 copies) and high (≥5 copies) gain of MYC was of adverse prognostic value compared to loss/normal (<2.5 copies) MYC (HR=1.50, 95% CI 1.13-1.98, Wald's p=0.004 and HR=1.45, 95% CI 1.07-1.97, p=0.016, respectively). Comparable results were observed for overall survival (OS) (HR=1.51, 95% CI 1.09-2.08, p=0.013 and HR=1.65, 95% CI 1.17-2.33, p=0.005, respectively). The comparison of neoplasms with CEP8 ratio ≥1.3 and polysomy 8 for MYC versus all others resulted in worse survival prognosis (HR=1.44, 95% CI 1.13-1.83, p=0.004), while tumors with nuclear protein overexpression were associated with better DFS (HR=0.77, 95% CI 0.60-0.99, p=0.039) and OS (HR=0.73, 95% CI 0.55-0.98, p=0.034). In HER2-enriched patients, MYC amplification was found to be an adverse prognostic factor for DFS (HR=2.11, 95% CI 1.09-4.07, p=0.026) and OS (HR=2.41, 95% CI 1.12-5.15, p=0.024). Treatment with paclitaxel was found to differentiate the effect of MYC: CEP8 ratio ≥1.3 and polysomy 8 in terms of DFS and OS in our total cohort. Among patients with CEP8 ratio ≥1.3 and polysomy 8, those treated with paclitaxel performed significantly better than those not treated, while among patients not treated with paclitaxel, those with CEP8 ratio ≥1.3 and polysomy 8 performed much worse than those with CEP8 ratio <1.3 or no polysomy 8. Conclusions: Our data suggest that MYC has prognostic and predictive value in patients with breast cancer. MYC amplification and MYC protein overexpression are detected in breast cancer patients and are of adverse prognostic value for DFS and OS. Polysomy 8 is also associated with worse prognosis. Treatment with paclitaxel in the adjuvant setting benefits breast cancer patients with MYC:CEP8 ratio ≥1.3 and polysomy 8. Citation Format: Batistatou A, Razis E, Bobos M, Tsolaki E, Timotheadou E, Alexopoulou Z, Goussia A, Gogas H, Koutras A, Karina M, Pentheroudakis G, Efstratiou I, Petraki K, Sotiropoulou M, Pavlakis K, Koletsa T, Kotoula V, Fountzilas G. Associations of MYC protein expression and gene status with breast cancer subtypes and outcome in patients treated with anthracycline-based adjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-50.