Abstract P4-12-07: CCND1 amplification in early breast cancer patients: Correlation with subtypes and prognosis

Abstract

Abstract Background: Mechanisms of progress and recurrence of early breast cancer (BC) have gained importance since several targeted therapeutic options in metastatic breast cancer have been introduced over the last years, especially in hormone receptor positive BC. This study investigates the amplification of cell cycle regulator cyclin D1 gene (CCND1) amplification as one possible progression mechanism. Patients & Methods: Patients from an unselected cohort of early BC patients were included into this study. A tissue microarray (TMA) was available for n=832 patients with early breast cancer. CCND1 amplification was assessed after FISH (Abbott Vysis LSI CCND1 SpectumOrange/CEP11 SpectrumGreen Probes Kit). A CCND1/CEP11-ratio ≥ 2.0 was considered as amplification. Staining was successful in 545 tumor cores. Amplification results were correlated with clinical patient and tumor characteristics and survival analyses were performed with regard to distant disease free survival and overall survival. Results: CCND1 amplification was found in 13.6% of patients. Triple negative, luminal A like, luminal B like and HER2 positive tumors were amplified in 7.5%, 7.8%, 18.6% and 15.7% respectively (p = 0.010). CCDN1 amplification was significantly associated with a higher grading and a higher body mass index. Furthermore an amplification was seen more frequently in lobular BC and ductal BC than other histological subtypes. Survival analysis showed a reduced DDFS for patients with CCDN1-amplification. 5 year DDFS rates were 90.6% for non-amplified tumors and 86.0% for amplified tumors (p, log-rank =0.066 ). 5 year OS rates were 93.0% for non-amplified tumors and 90.1% for amplified tumors (p, log-rank =0.119). Adjusted for age, tumor size, nodal status and molecular subtype, cox regression showed HR of 1.3 (95% CI: 0.76-2.5, p=0.46) for DDFS and a HR of 1.33 (95% CI: 0.7-2.53, p=0.38) for OS. Conclusion: With a 13.6% prevalence in all breast cancer patients, mainly present in luminal B like cancers, CCND1-amplification is a genetic aberration associated with an unfavorable prognosis. Within hormone receptor positive women CCDN1 amplification might play a role in treatment resistance mechanisms in early breast cancer patients. Citation Format: Hanf DC, Fasching PA, Villalobos IE, Gasparyan A, Wachter D, Santiago A, Guzman R, Weihbrecht S, Hanf V, Hartmann A, Beckmann MW, Press MF. CCND1 amplification in early breast cancer patients: Correlation with subtypes and prognosis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-12-07.