Breast cancers with a BRCA1-like DNA copy number profile recur less often than expected after high-dose alkylating chemotherapy

• Verfasst von: Schouten, Philip [VerfasserIn]
• Verfasst von: Marmé, Frederik [VerfasserIn]
• Verfasst von: Aulmann, Sebastian [VerfasserIn]
• Verfasst von: Sinn, Peter [VerfasserIn]
• Verfasst von: Essen, Hendrik F. van [VerfasserIn]
• Verfasst von: Ylstra, Bauke [VerfasserIn]
• Verfasst von: Hauptmann, Michael [VerfasserIn]
• Verfasst von: Schneeweiss, Andreas [VerfasserIn]
• Verfasst von: Linn, Sabine C. [VerfasserIn]
• Titel: Breast cancers with a BRCA1-like DNA copy number profile recur less often than expected after high-dose alkylating chemotherapy
• Verf.angabe: Philip C. Schouten, Frederik Marmé, Sebastian Aulmann, Hans-Peter Sinn, Hendrik F. van Essen, Bauke Ylstra, Michael Hauptmann, Andreas Schneeweiss, and Sabine C. Linn
• Jahr: 2015
• Jahr des Originals: 2014
• Umfang: 8 S.
• Fussnoten: Published online first December 5, 2014 ; Gesehen am 14.07.2020
• Titel Quelle: Enthalten in: Clinical cancer research
• Ort Quelle: Philadelphia, Pa. [u.a.] : AACR, 1995
• Jahr Quelle: 2015
• Band/Heft Quelle: 21(2015), 4, Seite 763-770
• ISSN Quelle: 1557-3265
• DOI: doi:10.1158/1078-0432.CCR-14-1894
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1724628194

Abstract

Purpose: Breast cancers in carriers of inactivating mutations of the BRCA1 gene carry a specific DNA copy-number signature (“BRCA1-like”). This signature is shared with cancers that inactivate BRCA1 through other mechanisms. Because BRCA1 is important in repair of DNA double-strand breaks through error-free homologous recombination, patients with a BRCA1-like tumor may benefit from high-dose alkylating (HD) chemotherapy, which induces DNA double-strand breaks. - Experimental Design: We investigated a single institution cohort of high-risk patients that received tandem HD chemotherapy schedule comprising ifosfamide, epirubicin, and carboplatin or conventional chemotherapy. We classified copy-number profiles to be BRCA1-like or non-BRCA1-like and analyzed clinical associations and performed survival analysis with a treatment by biomarker interaction design. - Results: BRCA1-like status associated with high-grade and triple-negative breast cancers. BRCA1-like cases benefitted from the HD compared with a conventional regimen on disease-free survival (DFS): [hazard ratio (HR), 0.05; 95% confidence interval (CI), 0.01-0.38; P = 0.003]; distant DFS (DDFS): (HR, 0.06; 95% CI, 0.01-0.43; P = 0.01); and overall survival (OS; HR, 0.15; 95% CI, 0.03-0.83; P = 0.03) after correction for prognostic factors. No such benefit was observed in the non-BRCA1-like cases on DFS (HR, 0.74; 95% CI, 0.38-1.46; P = 0.39), DDFS (HR, 0.79; 95% CI, 0.41-1.52; P = 0.47), and OS (HR, 0.93; 95% CI, 0.52-1.64; P = 0.79). The P values for interaction were 0.01 (DFS), 0.01 (DDFS), and 0.045 (OS). - Conclusions: BRCA1-like tumors recurred significantly less often after HD than conventional chemotherapy. BRCA1-like copy-number profile classification may be a predictive marker for HD alkylating chemotherapy. Clin Cancer Res; 1-8. ©2014 AACR.