Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

Anne-Sofie Schrohl Rasmussen, Maxime P. Look, Marion E. Meijer-van Gelder, John A. Foekens, Nils Brünner

    Publikation: KonferencebidragPosterForskning

    Abstract

     Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006) suggesting that TIMP-1 may be a predictive marker in breast cancer patients.

    Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen.

    Patients and Methods: 525 pre-menopausal lymph node-positive patients were included; 324 patients received adjuvant CMF, 99 received an adjuvant anthracycline-containing regimen and 102 had no adjuvant chemotherapy. Total TIMP-1 levels were measured by use of ELISA in cytosolic extracts of frozen primary tumors. Using the untreated patient group as a reference group, we analyzed the benefit of adjuvant CMF and anthracyclines in TIMP-1 high and low patients, respectively. The median TIMP-1 concentration was used to dichotomize patients into high and low TIMP-1 groups. End points were disease-free and overall survival (DFS, OS).

    Results: The median TIMP-1 level in the total patient group was 12,54 ng/mg of total protein (range, 0 - 112,9 ng/mg). TIMP-1 levels in subgroups according to adjuvant therapy were not significantly different (P=0,20). In a multivariate model including basic clinico-pathological parameters, TIMP-1 low and high patients benefited differentially from adjuvant CMF and anthracyclines when compared to untreated patients. In particular, patients with high tumor levels of TIMP-1 had little benefit from adjuvant anthracyclines. Hazard ratios (HR) and 95% confidence intervals (CI) are given in the table below for the analysis of DFS. A similar pattern was seen in the analyses of OS. In the group treated with CMF, both TIMP-1 low and high patients had significantly better survival than untreated patients (P<0,01). Among anthracycline-treated patients, those with TIMP-1 low tumors appear to benefit more from the adjuvant therapy than TIMP-1 high patients although these results did not reach significance in the present analyses.

     

     

    CMF-treated (HR, 95% CI)

    Anthracycline-treated (HR, 95% CI

    TIMP-1 low

    0,47 (0,31-0,72)

    0,65 (0,39-1,07)

    TIMP-1 high

    0,58 (0,39-0,87)

    0,90 (0,56-1,44)

     

    Conclusion: This study suggests that high tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however, is small and should be enlarged to confirm our results. In the group treated with CMF, all patients benefit from the therapy with TIMP-1 high patients having slightly less benefit from the therapy than TIMP-1 low patients.

    OriginalsprogEngelsk
    Publikationsdato2008
    StatusUdgivet - 2008
    BegivenhedSan Antonio Breast Cancer Symposium 2008 - San Antonio, Texas, USA
    Varighed: 10 dec. 200814 dec. 2008

    Konference

    KonferenceSan Antonio Breast Cancer Symposium 2008
    Land/OmrådeUSA
    BySan Antonio, Texas
    Periode10/12/200814/12/2008

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