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Tailored Chemo More Effective with Amplified Cancer Genes

Anthracycline-based chemotherapy more effective in women with breast cancer and HER-2/neu and TOP2A amplifications

WEDNESDAY, May 10 (HealthDay News) -- Breast cancer patients whose tumors have amplifications of two genes have better relapse-free survival if treated with individually tailored and dose-escalated adjuvant anthracycline-based chemotherapy, according to a report published online May 8 in the Journal of Clinical Oncology.

Jorma Isola, M.D., Ph.D., from Tampere University in Finland, and colleagues retrospectively analyzed stored tissue samples taken from 391 high-risk breast cancer patients for amplification of the HER-2/neu gene. Amplification of the TOP2A gene was also examined in tumors with HER-2/neu amplification. One group of women received nine courses of tailored and dose-escalated anthracycline-based chemotherapy with fluorouracil, epirubicin and cyclophosphamide. Another group received three to four courses of standard anthracycline-based chemotherapy followed by bone marrow-supported high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin.

The investigators found that HER-2/neu was amplified in 32.7 percent of tumors and that TOP2A was co-amplified in 37 percent of these tumors. While HER-2/neu amplification alone was significantly associated with short relapse-free and overall survival, TOP2A co-amplification was associated with better relapse-free survival, specifically for patients treated with nine courses of tailored and dose-escalated anthracycline-based chemotherapy.

"Co-amplification of HER-2/neu and TOP2A may define a subgroup of high-risk breast cancer patients who benefit from individually tailored and dose-escalated adjuvant anthracyclines," the authors conclude.

The study was funded by Amgen Inc., Roche Inc. and the former Pharmacia Inc., now part of Pfizer Inc.

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