| Autor: |
Philip C, Schouten, Oleg, Gluz, Nadia, Harbeck, Svjetlana, Mohrmann, Raihana, Diallo-Danebrock, Enrico, Pelz, Janneke, Kruizinga, Arno, Velds, Marja, Nieuwland, Ron M, Kerkhoven, Cornelia, Liedtke, Markus, Frick, Ronald, Kates, Sabine C, Linn, Ulrike, Nitz, Frederik, Marme |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
International journal of cancer. 139(4) |
| ISSN: |
1097-0215 |
| Popis: |
BRCA1 is an important protein in the repair of DNA double strand breaks (DSBs), which are induced by alkylating chemotherapy. A BRCA1-like DNA copy number signature derived from tumors with a BRCA1 mutation is indicative for impaired BRCA1 function and associated with good outcome after high dose (HD) and tandem HD DSB inducing chemotherapy. We investigated whether BRCA1-like status was a predictive biomarker in the WSG AM 01 trial. WSG AM 01 randomized high-risk breast cancer patients to induction (2× epirubicin-cyclophosphamide) followed by tandem HD chemotherapy with epirubicin, cyclophosphamide and thiotepa versus dose dense chemotherapy (4× epirubicin-cyclophospamide followed by 3× cyclophosphamide-methotrexate-5-fluorouracil). We generated copy number profiles for 143 tumors and classified them as being BRCA1-like or non-BRCA1-like. Twenty-six out of 143 patients were BRCA1-like. BRCA1-like status was associated with high grade and triple negative tumors. With regard to event-free-survival, the primary endpoint of the trial, patients with a BRCA1-like tumor had a hazard rate of 0.2, 95% confidence interval (CI): 0.07-0.63, p = 0.006. In the interaction analysis, the combination of BRCA1-like status and HD chemotherapy had a hazard rate of 0.19, 95% CI: 0.067-0.54, p = 0.003. Similar results were observed for overall survival. These findings suggest that BRCA1-like status is a predictor for benefit of tandem HD chemotherapy with epirubicin-thiotepa-cyclophosphamide. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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