Abstract 5184: Age interactions in the prognostic value of ALDH1 for clinical outcome in breast cancer
Authors: Esther M. De Kruijf, Sven J. D. Mieog, Esther Bastiaannet, Peter J. K. Kuppen, Anita Sajet, Vincent T.H.B.M. Smit, Cornelis J.H. van de Velde, Gerrit Jan Liefers
Journal: Cancer Research (2011)

Abstract Introduction: Breast cancer is increasingly becoming a disease affecting older women. Clinicopathological characteristics, such as tumor size and hormone receptor expression, have been found to differ considerably between elderly and younger breast cancer patients, which suggests different underlying tumor biology between both populations. Cancer stem cells have been found to be a predictor of worse outcome in various breast cancer studies. However, these studies were all performed on populations of relative young patients. The aim of this study was to compare the frequency and the prognostic effect of ALDH1-positive tumors, representing the stem cell fraction, in elderly patients to younger patients. Methods: Our study population (n=574) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1994. Tissue micro array slides were immunohistochemically stained for expression of ALDH1. The percentage of ALDH1-positive tumors cells was microscopically assessed by two independent observers in a blinded manner. Results: Complete lack of expression of ALDH1 was found in 40% of tumors. With increasing age more tumors showed complete absence of ALDH1 (logistic regression p-value &amp;lt;0.001). For comparison of the prognostic effect of ALDH1 between elderly and young patients, a cut-off point of 65 years was taken for age stratification and only patients who did not receive systemic treatment were selected. A statistically significant worse outcome was found for relapse free period (RFP) and relative survival (RS) in younger patients with ALDH1 tumor presence (logrank p-value: RFP 0.009; RS 0.008). This prognostic effect of ALDH1 was independent of known clinicopathological parameters in multivariate analysis (RFP: Hazard Ratio (HR) 1.71, p-value 0.021; RS: HR: 2.36, p-value 0.016). In elderly patients no statistically significant differences in outcome were found for ALDH1 expression (logrank p-value: RFP 0.138; RS 0.354). Interactions between the effect of age and ALDH1 presence on outcome were tested and revealed that the diverse prognostic effect of ALDH1 between young and elderly patients as found in the stratified analyses was a statistically significant difference (p-value: 0.007). Conclusion: ALDH1 presence is less frequently found in tumors of elderly breast cancer patients. In addition, presence of ALDH1 results in a worse outcome in young patients, but not elderly patients. This is the first study demonstrating that presence of ALDH1 activity and its prognostic effect is age-dependent. Our results support the hypothesis that breast cancer biology is different in elderly patients compared to their younger counterparts and emphasizes the importance of taking into consideration age-specific interactions in breast cancer research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5184. doi:10.1158/1538-7445.AM2011-5184