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. 2014 Nov 5;9(3):555–568. doi: 10.1016/j.molonc.2014.10.012

Figure 6.

Figure 6

Breast cancer‐specific survival analysis with respect to the novel DNA methylation defined subtypes, i.e. the Epi‐LumB and Epi‐Basal subtypes. A) Patients with breast tumors classified as either Epi‐LumB or Epi‐Basal on the basis of proxy CpG methylation markers (see Section 3.6 for details) are associated with reduced time to death due to breast cancer (i.e. breast cancer‐specific death). The lower panel displays a multivariate Cox's proportional hazards modeling of the survival data wherein the Epi‐LumB subtype was found to be an independent prognostic factor after adjustment for tumor size, lymph node metastases and age‐ and year at diagnosis. B) In analyzing a subset of the tumors wherein information on hormone receptor status (along with subtype‐specific markers) was available, we show that ER positive tumors classified as either Epi‐LumB (based on proxy‐methylation markers) or LumB (based on the Ki‐67 expression marker) represents an improvement above the LumB definition alone for predicting reduced time to breast cancer‐specific death. The lower panel shows the multivariate Cox's proportional hazards regression model for ER positive tumors classified as either Epi‐LumB (based on the proxy‐methylation markers) or LumB (based on high Ki‐67 expression) referred to as “high‐risk luminal tumors”, demonstrating the superior prognostic value in combining epigenetic and expression data above that of expression data alone. C) The Epi‐Basal subtype combined with the basal‐like expression‐based definition (using EGFR and CK5/6) was not significantly associated with reduced time to breast cancer‐specific deaths in ER negative breast cancers. However, as shown in the lower panel, the combination of epigenetic and expression data provides superior prognostic value of marginal statistical significance above that of expression data alone. Here, ER negative tumors classified as either Epi‐Basal (on the basis of proxy‐methylation markers) or basal‐like (based on expression of either EGFR or CK5/6), referred to as “high‐risk non‐luminal tumors” remain marginally significant for predicting breast cancer‐specific deaths while the basal‐like definition alone does not hold significant.