MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial.

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.

Déclaration de conflit d'intérêts

I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Schneeweiss reports grants from Celgene, grants from Roche, grants from AbbVie, grants from Molecular Partner, personal fees from Roche, personal fees from AstraZeneca, personal fees from Celgene, personal fees from Roche, personal fees from Roche, personal fees from Celgene, personal fees from Pfizer, personal fees from AstraZeneca, personal fees from Novartis, personal fees from MSD, personal fees from Tesaro, personal fees from Lilly, personal fees from Pfizer, other from Roche, outside the submitted work. Dr. v. Mackelenbergh reports travel grants and honoria from AstraZeneca, Amgen, Gebomic Health, Novartis, Lilly. Dr. Denkert reports personal fees from Novartis, personal fees from Roche, personal fees from MSD Oncology, from Daiichi Sankyo, grants from Myriad Genetics, other from Sividon Diagnostics / Myriad, outside the submitted work; In addition, Dr. Denkert has a patent EP18209672 pending, a patent EP20150702464 pending, and a patent Software (VMscope digital pathology) pending. All other authors declare no conflict of interest. We confirm that the patents do not alter our adherence to PLOS ONE policies on sharing data and materials. We would like to point out, that the patents had been added as general COI information but are not related to MGMT methylation.