DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status
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DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status. / Jurmeister, Philipp; Weber, Karsten; Villegas, Sonia; Karn, Thomas; Untch, Michael; Thieme, Anne; Müller, Volkmar; Taube, Eliane; Fasching, Peter; Schmitt, Wolfgang D; Marmé, Frederik; Stickeler, Elmar; Sinn, Bruno V; Jank, Paul; Schem, Christian; Klauschen, Frederick; van Mackelenbergh, Marion; Denkert, Carsten; Loibl, Sibylle; Capper, David.
In: CLIN EPIGENETICS, Vol. 13, No. 1, 184, 03.10.2021.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status
AU - Jurmeister, Philipp
AU - Weber, Karsten
AU - Villegas, Sonia
AU - Karn, Thomas
AU - Untch, Michael
AU - Thieme, Anne
AU - Müller, Volkmar
AU - Taube, Eliane
AU - Fasching, Peter
AU - Schmitt, Wolfgang D
AU - Marmé, Frederik
AU - Stickeler, Elmar
AU - Sinn, Bruno V
AU - Jank, Paul
AU - Schem, Christian
AU - Klauschen, Frederick
AU - van Mackelenbergh, Marion
AU - Denkert, Carsten
AU - Loibl, Sibylle
AU - Capper, David
N1 - © 2021. The Author(s).
PY - 2021/10/3
Y1 - 2021/10/3
N2 - 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.
AB - 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.
U2 - 10.1186/s13148-021-01176-5
DO - 10.1186/s13148-021-01176-5
M3 - SCORING: Journal article
C2 - 34602069
VL - 13
JO - CLIN EPIGENETICS
JF - CLIN EPIGENETICS
SN - 1868-7075
IS - 1
M1 - 184
ER -