MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial
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MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial. / Jank, Paul; Gehlhaar, Claire; Bianca, Lederer; Caterina, Fontanella; Andreas, Schneeweiss; Karn, Thomas; Marmé, Frederik; Sinn, Hans-Peter; van Mackelenbergh, Marion; Sinn, Bruno; Zahm, Dirk-Michael; Ingold-Heppner, Barbara; Schem, Christian; Stickeler, Elmar; Fasching, Peter A; Nekljudova, Valentina; Taube, Eliane Tabea; Heppner, Frank; Müller, Volkmar; Denkert, Carsten; Loibl, Sibylle.
In: PLOS ONE, Vol. 15, No. 8, 2020, p. e0238021.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial
AU - Jank, Paul
AU - Gehlhaar, Claire
AU - Bianca, Lederer
AU - Caterina, Fontanella
AU - Andreas, Schneeweiss
AU - Karn, Thomas
AU - Marmé, Frederik
AU - Sinn, Hans-Peter
AU - van Mackelenbergh, Marion
AU - Sinn, Bruno
AU - Zahm, Dirk-Michael
AU - Ingold-Heppner, Barbara
AU - Schem, Christian
AU - Stickeler, Elmar
AU - Fasching, Peter A
AU - Nekljudova, Valentina
AU - Taube, Eliane Tabea
AU - Heppner, Frank
AU - Müller, Volkmar
AU - Denkert, Carsten
AU - Loibl, Sibylle
PY - 2020
Y1 - 2020
N2 - Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA. In glioblastoma multiforme, MGMT methylation status is a predictive biomarker for increased response to temozolomide therapy. It has been suggested, that MGMT protein may have relevance for cellular adaptation and could have an influence on resistance to carboplatin therapy. We investigated the influence of MGMT promoter methylation on pathologic complete response and survival of patients with TNBC treated in the neoadjuvant GeparSixto trial. In 174 of 210 available TNBC tumors a valid MGMT promoter methylation status was determined by pyrosequencing of 5 CpG islands. In 21.8%, we detected a mean MGMT promoter methylation >10%. Overall, MGMT promoter methylation was not significantly associated with pathological complete response (pCR) rate. After stratification for the two therapy arms with and without Cb no statistically significant differences in therapy response rates between the two MGMT promoter methylation groups could be observed. Our results show that different MGMT promoter methylation status is not related to different chemotherapy response rates in the TNBC setting in GeparSixto.
AB - Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA. In glioblastoma multiforme, MGMT methylation status is a predictive biomarker for increased response to temozolomide therapy. It has been suggested, that MGMT protein may have relevance for cellular adaptation and could have an influence on resistance to carboplatin therapy. We investigated the influence of MGMT promoter methylation on pathologic complete response and survival of patients with TNBC treated in the neoadjuvant GeparSixto trial. In 174 of 210 available TNBC tumors a valid MGMT promoter methylation status was determined by pyrosequencing of 5 CpG islands. In 21.8%, we detected a mean MGMT promoter methylation >10%. Overall, MGMT promoter methylation was not significantly associated with pathological complete response (pCR) rate. After stratification for the two therapy arms with and without Cb no statistically significant differences in therapy response rates between the two MGMT promoter methylation groups could be observed. Our results show that different MGMT promoter methylation status is not related to different chemotherapy response rates in the TNBC setting in GeparSixto.
KW - Biopsy
KW - Clinical Trials as Topic
KW - Clinical Trials, Phase II as Topic
KW - Cohort Studies
KW - CpG Islands/genetics
KW - DNA Methylation
KW - DNA Modification Methylases/genetics
KW - DNA Repair Enzymes/genetics
KW - Humans
KW - Promoter Regions, Genetic/genetics
KW - Retrospective Studies
KW - Sequence Analysis, DNA
KW - Survival Analysis
KW - Triple Negative Breast Neoplasms/genetics
KW - Tumor Suppressor Proteins/genetics
U2 - 10.1371/journal.pone.0238021
DO - 10.1371/journal.pone.0238021
M3 - SCORING: Journal article
C2 - 32841306
VL - 15
SP - e0238021
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 8
ER -