Abstract
Young and elderly breast cancer patients are more likely to have a poorer outcome than middle‐aged patients. The intrinsic molecular features for this disparity are unclear. We obtained data from the Cancer Genome Atlas (TCGA) on May 15, 2017 to test the potential mediation effects of the molecular features on the association between age and prognosis with a four‐step approach. The relative contributions of the molecular features (PAM50 subtype, risk stratification, DNAm age, and mutations in TP53,PIK3CA,MLL3,CDH1,GATA3, and MAP3K1) to age disparities in survival were estimated by Cox proportional hazard models with or without the features. Young patients were significantly more likely to have basal‐like subtype, GATA3 mutations, and younger DNA methylation (DNAm) age than middle‐aged patients (P < .05). Both the young and elderly patients had a significantly increased risk of breast cancer recurrence after adjusted by race, tumor size, and node status (Hazard ratio [HR] (95% confidence interval [CI]): 2.81 [1.44, 5.45], 2.37 [1.45, 3.89], respectively). This increased risk was weakened in the young patients after further adjustments in the molecular features, particularly basal‐like subtype, GATA3 mutations, and DNAm age (HR [95%CI]: 1.87 [0.81, 4.32]), resulting in 33.5% decreased risk of recurrence. Meanwhile, the adjustments of the molecular features did not alter the recurrence risk for the elderly patients. Compared with middle‐aged patients of breast cancer, poorer prognosis of elderly patients may be caused by aging, while poorer prognosis of young patients was probably mediated through intrinsic characteristics, such as basal‐like subtype, GATA3 mutations, and DNAm age of the cancerous tissues.
Highlights
Breast cancer is known as the most prevalent cancer type and one of the leading causes of cancer death among females worldwide.[1]
We investigated the impacts of the molecular features in young vs elderly breast cancer patients, such as gene and miRNA expression profiles, somatic mutations, and DNA methylation profiling, on survival disparities by age at diagnosis through the breast cancer clinical and molecular data from the Cancer Genome Atlas (TCGA)
It may be understandable and reasonable that elderly breast cancer patients had a worse prognosis than middle- aged patients due to the impaired capacity with aging or undertreatment.[7,10,34,35]
Summary
Breast cancer is known as the most prevalent cancer type and one of the leading causes of cancer death among females worldwide.[1] The incidence has been increasing worldwide and may continue to rise in the future.[2] The overall survival time has been prolonged because of the advances in the pharmacological and surgical therapy, but there is still space to improve the prognosis.[3,4] Plenty of studies have explored the prognostic factors of breast cancer,[4] and one of the intriguing findings is that the younger and older patients had a poorer outcome than the middle-aged patients.[5]. We investigated the impacts of the molecular features in young vs elderly breast cancer patients, such as gene and miRNA expression profiles, somatic mutations, and DNA methylation profiling, on survival disparities by age at diagnosis through the breast cancer clinical and molecular data from the Cancer Genome Atlas (TCGA)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
