In Response to “Drug Metabolizing Enzyme Polymorphisms Predict Clinical Outcome in a Node-Positive Breast Cancer Cohort”

2007 ◽  
Vol 25 (35) ◽  
pp. 5675-5677 ◽  
Author(s):  
Angela DeMichele ◽  
Phyllis Gimotty ◽  
Jeffrey Botbyl ◽  
Richard Aplenc ◽  
Theresa Colligon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Node Positive ◽  
Enzyme Polymorphisms ◽  
Drug Metabolizing Enzyme ◽  
Breast Cancer Cohort ◽  
Metabolizing Enzyme ◽  
Positive Breast Cancer

HER-2/neu oncogene protein and prognosis in breast cancer.

1989 ◽  
Vol 7 (8) ◽  
pp. 1120-1128 ◽  
Author(s):  
A K Tandon ◽  
G M Clark ◽  
G C Chamness ◽  
A Ullrich ◽  
W L McGuire
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Node Negative ◽  
Node Positive ◽  
Her 2 ◽  
Neu Oncogene ◽  
Disease Free ◽  
Oncogene Protein ◽  
Positive Breast Cancer

Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.

Correlation of levels of Akt phosphorylation at Ser473 with benefit from paclitaxel chemotherapy in NSABP B-28 patients with node-positive breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 537-537
Author(s):  
S. X. Yang ◽  
J. P. Costantino ◽  
D. Nguyen ◽  
J. Jeong ◽  
E. P. Mamounas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Imaging System ◽  
Statistical Significance ◽  
Her2 Status ◽  
Primary Tumors ◽  
Akt Phosphorylation ◽  
Node Positive ◽  
Sequential Addition ◽  
Positive Breast Cancer

537 Background: We investigated the levels of tumor phospho-Akt(Ser473) (pAkt) and treatment outcome of patients with node-positive breast cancer after adjuvant treatment with doxorubicin/cyclophosphamide (AC) followed by four cycles of paclitaxel (PTX) (AC→PTX) compared with AC chemotherapy alone in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 trial. Methods: The primary tumors on B-28 tissue microarray were available from 1581 of 3060 patients enrolled. pAkt status was examined by immunohistochemistry with the antibody to pAkt(Ser473) (Cell Signaling Technology) at the National Cancer Institute. Levels of pAkt were quantitatively scored with the assistance of an Automated Digital Imaging System blinded to clinical outcome, and categorized by the staining index (intensity X % of staining /100) of > 2 (high) and ≤ 2 (low). The association between tumor pAkt level and clinical outcome at 10 years was assessed using multivariate Cox modeling adjusting for age, tumor size, number of positive nodes, tumor grade, estrogen receptor and HER2 status. Results: Among patients with low tumor pAkt levels (n = 975), there was no DFS difference between those treated with or without PTX (adjusted HR = 1.02, p = 0.81). However, among patients with high tumor pAkt levels (n = 606), those treated with AC→PTX had a 26% reduction in DFS event rate compared to those treated with AC only (adjusted HR = 0.74, p = 0.02). There was no OS difference between treatment groups for those with low pAkt cancer (HR = 0.97, p = 0.80). In patients with high pAkt cancer, those treated with AC→PTX had a 20% reduction in death rate compared to those treated with AC only but this difference did not reach statistical significance (adjusted HR = 0.80, p = 0.17). Conclusions: High levels of Akt phosphorylation at Ser473 independently predict a DFS benefit from the sequential addition of paclitaxel to adjuvant doxorubicin plus cyclophosphamide in node-positive breast cancer. Patients with low levels of pAkt breast cancer may not benefit from the sequential addition of PTX to doxorubicin plus cyclophosphamide. [Table: see text]

Drug-Metabolizing Enzyme Polymorphisms Predict Clinical Outcome in a Node-Positive Breast Cancer Cohort

2005 ◽  
Vol 23 (24) ◽  
pp. 5552-5559 ◽  
Author(s):  
Angela DeMichele ◽  
Richard Aplenc ◽  
Jeffrey Botbyl ◽  
Theresa Colligan ◽  
Lisa Wray ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Clinical Outcome ◽  
High Dose ◽  
Group Status ◽  
Genotype Group ◽  
Functional Polymorphisms ◽  
Node Positive ◽  
Positive Breast Cancer

Purpose Adjuvant chemotherapy cures only a subset of women with nonmetastatic breast cancer. Genotypes in drug-metabolizing enzymes, including functional polymorphisms in cytochrome P450 (CYP) and glutathione S-transferases (GST), may predict treatment-related outcomes. Patients and Methods We examined CYP3A4*1B, CYP3A5*3, and deletions in GST μ (GSTM1) and θ (GSTT1), as well as a priori–defined combinations of polymorphisms in these genes. Using a cohort of 90 node-positive breast cancer patients who received anthracycline-based adjuvant chemotherapy followed by high-dose multiagent chemotherapy with stem-cell rescue, we estimated the effect of genotype and other known prognostic factors on disease-free survival (DFS) and overall survival (OS). Results Patients who carried homozygous CYP3A4*1B and CYP3A5*3 variants and did not carry homozygous deletions in both GSTM1 and GSTT1 (denoted low-drug genotype group) had a 4.9-fold poorer DFS (P = .021) and a four-fold poorer OS (P = .031) compared with individuals who did not carry any CYP3A4*1B or CYP3A5*3 variants but had deletions in both GSTT1 and GSTM1 (denoted high-drug genotype group). After adjustment for other significant prognostic factors, the low-drug genotype group retained a significantly poorer DFS (hazard ratio [HR] = 4.9; 95% CI, 1.7 to 14.6; P = .004) and OS (HR = 4.8; 95% CI, 1.8 to 12.9; P = .002) compared with the high- and intermediate-drug combined genotype group. In the multivariate model, having low-drug genotype group status had a greater impact on clinical outcome than estrogen receptor status. Conclusion Combined genotypes at CYP3A4, CYP3A5, GSTM1, and GSTT1 influence the probability of treatment failure after high-dose adjuvant chemotherapy for node-positive breast cancer.

C-Met overexpression in node-positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu

2004 ◽  
Vol 113 (4) ◽  
pp. 678-682 ◽  
Author(s):  
Ernst Lengyel ◽  
Dieter Prechtel ◽  
James H. Resau ◽  
Katja Gauger ◽  
Anita Welk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Poor Clinical Outcome ◽  
Node Positive ◽  
Positive Breast Cancer
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