Prognostic value of breast cancer m-RNA transcripts (Ts) detection by RT-PCR in GCSF stimulated peripheral blood (PB) after adjuvant chemotherapy (ACT) in high-risk breast cancer patients (HRBCP)

532 Background: The primary objective of the study was to evaluate TOP2A as predictive marker for adjuvant treatment with epirubicin in high-risk breast cancer patients. As a secondary objective the prognostic characteristics of TOP2A gene aberrations was investigated. The data presented on the predictive properties is a follow-up to the data previously published (Knoop et al, J Clin Oncol 2005; 23: 7483–90). Methods: 962 pre- and postmenopausal high-risk Danish patients were enrolled in the DBCG89D protocol. The patients were randomly allocated to either 9 × CMF (cyclophosphamide, methotrexate, 5-flurouracil) (n=495) or 9 × CEF (cyclophosphamide, epirubicin, 5-flurouracil) (n=467) every 3 weeks. Tumor-tissue was available from 806 patients (84%). The tumors were analyzed for TOP2A copy number changes with the TOP2A FISH pharmDx Kit (Dako, Glostrup). Recurrence-free survival (RFS) was used as primary end-point. Univariate and multivariate statistics were used to assess the predictive and prognostic properties of the TOP2A gene aberrations. Results: The TOP2A test was successful in 96% of the patients. Ninety-two (12.0%) patients were found to have TOP2A amplified tumors, and 86 (11.1%) to have TOP2A deleted tumors. For the primary study endpoint (RFS) a significant predictive value of TOP2A gene amplifications was found (HR=0.39; CI: 0.22–0.70; p=0.0017). A similar trend was seen with respect to TOP2A deletions (HR=0.61; CI: 0.35–1.07; p=0.082). TOP2A gene aberrations were significantly associated with several established prognostic factors and had independent prognostic value, associated with a significant worse prognosis both for RFS (p=0.036) and overall survival (p=0.012). Conclusions: The DBCG89D study has shown that TOP2A amplifications are associated with a favorable outcome of adjuvant treatment with epirubicin in primary breast cancer. Further, TOP2A aberrations demonstrated an independent prognostic value. [Table: see text]

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Patient selection in high-dose chemotherapy trials: relevance in high-risk breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.10.3178 ◽

1997 ◽

Vol 15 (10) ◽

pp. 3178-3184 ◽

Cited By ~ 60

Author(s):

R García-Carbonero ◽

M Hidalgo ◽

L Paz-Ares ◽

J Calzas ◽

H Gómez ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Cancer Patients ◽

High Dose ◽

Breast Cancer Patients ◽

Short Term ◽

High Risk Breast Cancer ◽

High Risk Breast ◽

Risk Breast Cancer

PURPOSE To evaluate the impact of the selection criteria that are used in current high-dose consolidation chemotherapy (HDCT) trials on the outcome of high-risk breast cancer patients treated with conventional adjuvant chemotherapy. PATIENTS AND METHODS From 1975 to 1995, 265 breast cancer patients at our institution showed involvement of ten or more positive axillary lymph nodes. Of these, 171 received standard adjuvant combination chemotherapy, but not HDCT consolidation, and were the subjects of our study. One hundred twenty-eight patients met the standard selection criteria for HDCT with hematological support (< 60 years, no significant concomitant disease, and no progression during adjuvant treatment), whereas 43 did not. Clinical outcome was analyzed by using disease-free survival (DFS) and overall survival (OS) as endpoints. To provide an assessment of the short-term efficacy of HDCT, we also evaluated the outcome in a cohort of 39 patients from the last 4 years who met the criteria for, and were actually treated with, HDCT after adjuvant chemotherapy. RESULTS With a median follow-up of 4.4 years (range, 0.7 to 17.2 years), 112 of the 171 patients have had a relapse, and 87 have died. The estimated 5-year DFS was 32.3%, and OS was 49.4%. DFS was significantly higher for patients who met the HDCT criteria (36.6% at 5 years) than for those who did not (15.8% at 5 years; P < .05). OS was also significantly more favorable in patients meeting HDCT criteria (55.4% at 5 years) than in patients not meeting HDCT criteria (22.7% at 5 years; P < .01). We performed a multivariate analysis to adjust for other potential prognostic factors and found that meeting the HDCT criteria and having undergone locoregional radiotherapy were the only significant independent predictors for DFS and OS. Finally, we compared the outcome of the 128 patients who met the HDCT criteria and were treated with conventional adjuvant chemotherapy only with that of the 39 patients who met the criteria and who actually underwent HDCT, and we did not observe significant differences in the DFS or OS between these groups. CONCLUSIONS Meeting HDCT inclusion criteria is an independent indicator of favorable prognosis in high-risk breast cancer patients. The selection of patients by these criteria may explain, at least in part, the promising short-term results of nonrandomized adjuvant HDCT trials in high-risk breast cancer.

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