Abstract P2-05-33: Refining the prognostic value of Ki67 biomarker by ataxia telangiectasia mutated (ATM) status in a retrospective study of early stage hormone receptor positive breast cancer

Abstract

Abstract Purpose: The current study was designed to investigate the combined influence of ataxia telangiectasia mutated (ATM) and Ki67 on clinical outcome in early stage hormone receptor positive breast cancer (ES-HPBC), particularly in patients with smaller tumors (< 4 cm) and fewer than four positive lymph nodes. Methods: Formalin-fixed paraffin-embedded specimens of resected primary breast tumors from 532 patients diagnosed with early stage breast cancer were used to construct a tissue microarray. Samples from 297 patients were suitable for final statistical analysis. We detected ATM and Ki67 proteins using immunohistochemistry and quantified their expression with digital image analysis. Data on expression levels were subsequently correlated with clinical outcome. Results: Remarkably, ATM expression was useful to stratify the low Ki67 group into subgroups with better or poorer prognosis. Specifically, in the low Ki67 subgroup defined as having smaller tumors and no positive nodes, patients with high ATM expression showed better outcome than those with low ATM, with estimated survival rates of 96% and 89% respectively at 15 years follow up (p = 0.04). Similarly, low-Ki67 patients with smaller tumors, 1-3 positive nodes and high ATM also had significantly better outcomes than their low ATM counterparts, with estimated survival rates of 88% and 46% respectively (p=0.03) at 15 years follow up. Multivariable analysis indicated that the combination of high ATM and low Ki67 is prognostic of improved survival, independent of tumor size, grade, and lymph node status (p = 0.02). Low Ki67/high ATM expression independently predicts favorable disease survival in a multivariate model in low Ki67 subgroup of ES-HPBC (Stage I-III)Variablesp valueHR (95%CI)Low Ki67/high ATM vs Low Ki67/low ATM0.020.36 (0.15-0.88)ize (T1/2 vs T3/4)0.010.16 (0.04-0.69)LN status (- vs +)0.140.49 (0.20-1.25)LVI (_- vs +)0.160.51 (0.20-1.31)Grade (1/2 vs 3)<0.00010.28 (0.11-0.67)Age (<65 vs >65)0.010.26 (0.10-0.74) Conclusions: These data suggest that the prognostic value of Ki67 can be improved by analyzing ATM expression in ES-HPBC. Citation Format: Feng X, Li H, Kornarga E, Dean M, Lees-Miller S, Riabowol K, Magliocco A, Morris D, Watson P, Enwere E, Bebb G, Paterson A. Refining the prognostic value of Ki67 biomarker by ataxia telangiectasia mutated (ATM) status in a retrospective study of early stage hormone receptor positive breast cancer [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 P2-05-33.