scholarly journals Locally advanced breast cancer as a model for biomarkers research

2003 ◽  
Vol 11 (3) ◽  
pp. 135-138
Author(s):  
Dragica Nikolic-Vukosavljevic
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Molecular Biomarkers ◽  
Advanced Breast ◽  
In Vivo Model ◽  
Breast Cancer Growth ◽  
Er Alpha

The presence of the tumor in locally advanced breast cancer as an in vivo model offers the possibility of studying the effect of primary anticancer therapy on biological parameters. The hypothesis is that changes in certain molecular biomarkers, particular determinants of tumor growth such as proliferation or apoptosis, or molecular biomarkers of angiogenesis modulation, may predict clinical outcome. In this review, numerous molecular biomarkers of proliferation (ER alpha and ER beta, PR, EGF-R family) and apoptosis (p53, Bcl-2 family), as well as molecular biomarkers of angiogenesis (FGF, VEGF) are discussed for their possible role in locally advanced breast cancer growth.

Targeted Inhibition of Farnesyltransferase in Locally Advanced Breast Cancer: A Phase I and II Trial of Tipifarnib Plus Dose-Dense Doxorubicin and Cyclophosphamide

2006 ◽  
Vol 24 (19) ◽  
pp. 3013-3018 ◽  
Author(s):  
Joseph A. Sparano ◽  
Stacy Moulder ◽  
Aslamuzzaman Kazi ◽  
Linda Vahdat ◽  
Tianhong Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Enzyme Activity ◽  
Advanced Breast Cancer ◽  
Primary Tumor ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Advanced Breast ◽  
Preoperative Treatment ◽  
Dose Dense

Purpose To determine the recommended phase II dose (RPTD) of the farnesyltransferase (FTase) inhibitor tipifarnib when combined with doxorubicin and cyclophosphamide (AC) in patients with advanced breast cancer, the pathologic complete response (pCR) rate after preoperative treatment with four cycles of the combination in locally advanced breast cancer (LABC), and the effect of tipifarnib on primary tumor FTase enzyme activity in vivo. Patients and Methods Thirty-two patients with metastatic breast cancer (n = 11) or LABC (n = 21) received AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously on day 1 plus tipifarnib (100, 200, or 300 mg bid for 6 to 14 days) without (n = 2) or with (n = 30) granulocyte colony-stimulating factor (G-CSF) for up to four cycles. Patients with LABC underwent surgery after up to four cycles of the combination. Results When combined with AC every 2 weeks plus G-CSF, the RPTD of tipifarnib was 200 mg bid administered on days 2 to 7. Seven (33%) of 21 patients (95% CI, 15% to 55%) with LABC treated with up to four cycles of the combination at the RPTD had a pCR in the breast at surgery. The five patients had serial biopsies that demonstrated at least 50% FTase enzyme inhibition in the primary tumor (median, 100%; range, 55% to 100%) after tipifarnib. Conclusion Tipifarnib may be safely combined with dose-dense AC using a dose and schedule that significantly inhibits FTase enzyme activity in human breast cancer in vivo and may enhance the pCR rate after four cycles of preoperative dose-dense AC.

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