title: BRCA1 promoter methylation is a marker of better response to anthracycline-based therapy in sporadic TNBC.
abstract: The aim of the current study was to investigate the role of BRCA1 gene aberrations in sporadic triple-negative breast cancer (TNBC) and its impact on anthracycline-based therapy. BRCA1 promoter methylation was analyzed in 70 TNBC and compared with the clinical and pathologic characteristics. As a control group, we used 70 patients with non-TNBC. BRCA1 promoter methylation was observed in 65.2 % of patients and was similar in both groups. BRCA1 promoter methylation was associated with decreased intensity of BRCA1 protein expression (P = 0.002) and significant increase of median disease-free survival (DFS) of TNBC patients receiving adjuvant anthracycline-based chemotherapy (P = 0.001). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to DFS (HR 0.224; 95 % CI 0.092-0.546, P = 0.001) in TNBC after adjustment for other prognostic factors. In contrast, in non-TNBC, BRCA1 promoter methylation was not associated with any clinical and pathologic parameters. BRCA1 promoter methylation is a common mechanism of BRCA1 gene aberration in sporadic breast cancer and is predictive for better response to anthracycline-based therapies.
authors.affiliation: Department of Obstetrics and Gynecology, Otto-von-Guericke University, G.-Hauptmann Str. 35, 39108, Magdeburg, Germany, tanja.ignatov@med.ovgu.de.
authors.forename: T
authors.initials: T
authors.lastname: Ignatov
authors.forename: A
authors.initials: A
authors.lastname: Poehlmann
authors.forename: A
authors.initials: A
authors.lastname: Ignatov
authors.forename: A
authors.initials: A
authors.lastname: Schinlauer
authors.forename: S D
authors.initials: SD
authors.lastname: Costa
authors.forename: A
authors.initials: A
authors.lastname: Roessner
authors.forename: T
authors.initials: T
authors.lastname: Kalinski
authors.forename: J
authors.initials: J
authors.lastname: Bischoff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D047368:Tumor Burden
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D019313:BRCA1 Protein