Prediction of Breast Cancer Survival Using Clinical and Genetic Markers by Tumor Subtypes

Abstract

PurposeTo identify the genetic variants associated with breast cancer survival, a genome-wide association study (GWAS) was conducted of Korean breast cancer patients.MethodsFrom the Seoul Breast Cancer Study (SEBCS), 3,226 patients with breast cancer (1,732 in the discovery and 1,494 in the replication set) were included in a two-stage GWAS on disease-free survival (DFS) by tumor subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). The associations of the re-classified combined prognostic markers through recursive partitioning analysis (RPA) of DFS for breast cancer were assessed with the Cox proportional hazard model. The prognostic predictive values of the clinical and genetic models were evaluated by Harrell’s C.ResultsIn the two-stage GWAS stratified by tumor subtypes, rs166870 and rs10825036 were consistently associated with DFS in the HR+ HER2- and HR- HER2- breast cancer subtypes, respectively (P rs166870=2.88×10-7 and P rs10825036=3.54×10-7 in the combined set). When patients were classified by the RPA in each subtype, genetic factors contributed significantly to differentiating the high risk group associated with DFS inbreast cancer, specifically the HR+ HER2- (P discovery=1.18×10-8 and P replication=2.08×10-5) and HR- HRE2- subtypes (P discovery=2.35×10-4 and P replication=2.60×10-2). The inclusion of the SNPs tended to improve the performance of the prognostic models consisting of age, TNM stage and tumor subtypes based on ER, PR, and HER2 status.ConclusionCombined prognostic markers that include clinical and genetic factors by tumor subtypes could improve the prediction of survival in breast cancer.

Revisiting Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Cancer: Saint or Sinner?

“…The abnormally elevated levels of NGAL in most cancers appear significantly correlated with disease severity and poor survival [ 1 , 4 , 7 , 8 , 9 , 14 , 21 , 25 ]. For example, studies on breast cancer suggest the usefulness of serum NGAL in monitoring disease progression [ 22 ] and the association of serum NGAL with reduced survival [ 23 ]. NGAL appears to be a diagnostic biomarker of advanced or recurrent ovarian cancer [ 27 ] and pancreatic cancer [ 36 ].…”

Increased Cellular Levels of MicroRNA-9 and MicroRNA-221 Correlate with Cancer Stemness and Predict Poor Outcome in Human Breast Cancer

“…The use of ER, PR, and HER2 has become a common and acceptable way for clinicians to predict breast cancer prognosis and prescribe a suitable therapeutic regimen for women living with the disease [42,43]. A recent investigation of miRNAs in stem-cell biology revealed the involvement of miR-200 in the organization of miRNA clusters and its differential expression in human breast cancer stem cells compared with normal mammary stem cells; therefore, a better understanding of the molecular mechanisms underlying the miR-200 family miRNAs with respect to how their cellular levels and consequent loss of control of self-renewal and EMT in breast cancer stem cell-like cells can predict patient prognosis [44].…”

Histopathological Characteristics: Clinical Course of Breast Cancer Subtypes Depending on the ER(+) (−)/PR(+) (−) Receptor Status

“…Genetic testing is not commonly performed to determine tumor subtypes or select treatment, and treatment alternatives are usually applied based on the receptor and clinicopathological data. However, genetic variations and ethnic differences may alter the prognosis of the disease [25]. Consequently, different response rates have been observed in many of the studies.…”