Related Experiment Video
Updated: Oct 18, 2025
Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression,
Philipp Jurmeister1,2,3,4, Karsten Weber5, Sonia Villegas6
1Institute of Pathology, Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117, Berlin, Germany. philipp.jurmeister@med.uni-muenchen.de.
Background:
Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1-10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation profiling on 23 LowHR breast cancer specimens, including 13 samples with HER2 amplification and compared our results with a reference breast cancer cohort from The Cancer Genome Atlas to clarify the status for this infrequent but important patient subgroup.
Results:
In unsupervised clustering and dimensionality reduction, breast cancers with low hormone receptor expression that lacked HER2 amplification usually clustered with triple negative breast cancer (TNBC) reference samples (8/10; "LowHR TNBC-like"). In contrast, most specimens with low hormone receptor expression and HER2 amplification grouped with hormone receptor positive cancers (11/13; "LowHR HRpos-like"). We observed highly similar DNA methylation patterns of LowHR TNBC-like samples and true TNBCs. Furthermore, the Ki67 proliferation index of LowHR TNBC-like samples and clinical outcome parameters were more similar to TNBCs and differed from LowHR HRpos-like cases.
Conclusions:
We here demonstrate that LowHR breast cancer comprises two epigenetically distinct groups. Our data strongly suggest that LowHR TNBC-like samples are molecularly, histologically and clinically closely related to TNBC, while LowHR HRpos-like specimens are closely related to hormone receptor positive tumors.
