Abstract P6-08-24: Age independently predicts worse disease-specific survival in patients diagnosed with invasive breast cancers at 50 years of age or older but not younger
Authors: Ru Yuanbin , Mural Richard J , Steeg Patricia S , Rui Hallgeir , Shriver Craig D , Hu Hai 
Published: May 2015

Abstract
BACKGROUND
It has been reported that women diagnosed with invasive breast cancer (IBC) in their 50s or 60s have better survival than either younger or older women. Young women with IBCs often have a more aggressive phenotype which contributes to worse survival. But there is supporting evidence in the literature for both sides whether age alone is an intrinsic driver of the poor outcome in young women. The availability of large-scale IBC data provided a good opportunity to address this issue.
METHODS
Clinicopathologic and gene expression data from 2 public datasets, including METABRIC from the European Genome-Phenome Archive (n=1992) and The Cancer Genome Atlas-Breast Cancer project (TCGA-BC, n=980) from National Cancer Institute, were used in this study. PAM50 was used to derive intrinsic subtypes based on microarray and RNA-Seq data. For a given phenotype, Fisher’s exact test was used for its association with age, and 2-sample test for equality of proportions with continuity correction between young and older patients. Kolmogorov-Smirnov’s test was used for equality of age distributions between phenotypes. Disease-specific survival (DSS) was examined for relationship with age, adjusted for race, AJCC stage, nodal metastasis, tumor size, grade, and subtype where applicable. Kaplan-Meier estimate and log-rank test were used to generate and compare survival curves, respectively. Cox proportional hazards model was used for univariate and multivariate analyses and to calculate hazard ratios (HRs).
RESULTS
Firstly, we confirmed that more aggressive IBCs were enriched in young patients. Younger patients (&lt;50 years) were diagnosed with more basal-like subtype (P&lt;0.05) and more node+ diseases (P&lt;0.05) compared with their older counterparts (≥50 years) in both datasets. Secondly, we found no significant difference in DSS between these 2 age groups after adjusting for subtype and other clinicopathologic variables. Finally, we examined the effect of age on DSS within the young and older patient groups separately. In the young patient group, age was not predictive of DSS in multivariate models in either datasets. However, in the older patient group, after adjusting for the effects of other clinicopathologic variables in the METABRIC dataset, the continuously increasing age was associated with worse DSS in all subtypes (HR=1.018, P=0.0076), as well as Luminal A (HR=1.041, P=0.00074) and Luminal B (HR=1.021, P=0.047) but not HER2+ or basal-like subtype in this age group. The results were validated in the TCGA-BC data (HR=1.055 and P=0.0052 in all older patients; HR=1.070 and P=0.066 in Luminal A; HR=1.081 and P=0.034 in Luminal B).
CONCLUSION
Our results supported that age was not an independent predictor of DSS for patients diagnosed at age &lt;50 years, and the worse outcome of this age group was apparently a surrogate for more aggressive IBC phenotype. Our observation that age was an independent predictor of worse DSS in the older patient group, especially patients with Luminal A and B but not the other subtypes, warrants further molecular studies.
The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Defense, or U.S. Government.
Citation Format: Yuanbin Ru, Richard J Mural, Patricia S Steeg, Hallgeir Rui, Craig D Shriver, Hai Hu. Age independently predicts worse disease-specific survival in patients diagnosed with invasive breast cancers at 50 years of age or older but not younger [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-24.