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.

scholarly journals Akt Phosphorylation at Ser473 Predicts Benefit of Paclitaxel Chemotherapy in Node-Positive Breast Cancer

2010 ◽  
Vol 28 (18) ◽  
pp. 2974-2981 ◽  
Author(s):  
Sherry X. Yang ◽  
Joseph P. Costantino ◽  
Chungyeul Kim ◽  
Eleftherios P. Mamounas ◽  
Dat Nguyen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Disease Free Survival ◽  
Primary Tumors ◽  
Free Survival ◽  
Node Positive ◽  
Sequential Addition ◽  
Disease Free ◽  
Positive Breast Cancer

Purpose We tested the hypothesis that Akt-Ser473 phosphorylation (pAkt) predicts benefit from the sequential addition of paclitaxel to adjuvant doxorubicin plus cyclophosphamide (AC) chemotherapy in patients with node-positive breast cancer participating in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 trial. Patients and Methods Primary tumors from the NSABP B-28 trial tissue microarray were available from 1,581 of 3,060 patients who were randomly assigned to receive either four cycles of AC alone or followed by four cycles of paclitaxel. Immunohistochemistry and quantitative analysis of pAkt were performed at the National Cancer Institute blinded to clinical outcome. Association between pAkt and clinical outcome was assessed using multivariate Cox modeling adjusting for age, tumor size, number of positive nodes, tumor grade, estrogen receptor status, and human epidermal growth factor receptor 2 status. Results With a median follow-up of 9.1 years, there were no differences in disease-free survival (adjusted hazard ratio [HR], 1.02; P = .81) or overall survival (HR, 0.97; P = .80) with and without receiving paclitaxel among 975 patients with pAkt-negative tumors. In 606 patients with pAkt-positive tumors, the sequential addition of paclitaxel resulted in a 26% improvement in disease-free survival (HR, 0.74; P = .02) or a 20% improvement in overall survival (HR, 0.80; P = .17). Conclusion pAkt significantly predicts disease-free benefit from the sequential addition of paclitaxel to AC chemotherapy in patients with node-positive breast cancer. Patients with pAkt-negative breast tumors do not appear to benefit from the addition of paclitaxel.

Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group.

1993 ◽  
Vol 11 (10) ◽  
pp. 1936-1942 ◽  
Author(s):  
R Seshadri ◽  
F A Firgaira ◽  
D J Horsfall ◽  
K McCaul ◽  
V Setlur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Tumor Size ◽  
Copy Number ◽  
Node Negative ◽  
Node Positive ◽  
Oncogene Amplification ◽  
Her 2 ◽  
Neu Oncogene

PURPOSE To determine prospectively the prognostic significance of HER-2/neu oncogene amplification in the primary tumors of breast cancer patients. METHODS HER-2/neu amplification in tumor DNA was determined by the slot-blot technique in 1,056 patients with breast cancer (stage I to III) diagnosed between 1987 and 1990. Parameters such as estrogen receptor (ER) and progesterone receptor (PgR) levels, tumor size, axillary nodal involvement, tumor grade, and time to relapse were prospectively obtained. RESULTS HER-2/neu oncogene amplification, > or = 2, > or = 3, and > or = 5 copy number, was detected in 21%, 11%, and 7% of patients, respectively. In a test set of 529 patients, Cox multivariate analysis showed HER-2/neu copy number > or = 3 or > or = 5 was associated with shorter disease-free survival (DFS) duration. HER-2/neu copy number > or = 3 correlated significantly with pathologic stage of disease, number of axillary nodes with tumor, histologic type, and absence of ER and PgR. For all patients, after a median follow-up duration of 39 months, Kaplan-Meier univariate analysis indicated that tumor oncogene copy number > or = 3 correlated with shorter DFS in both node-negative and node-positive patients. In Cox multivariate analysis, HER-2/neu copy number > or = 3 was associated with shorter DFS, independent of nodal status, ER level, and tumor size. CONCLUSION Although the follow-up duration of this study is relatively short, we conclude that HER-2/neu amplification is an independent predictor of shorter DFS in both node-negative and node-positive patients.

Short-course FAC-M versus 1 year of CMFVP in node-positive, hormone receptor-negative breast cancer: an intergroup study.

1995 ◽  
Vol 13 (4) ◽  
pp. 831-839 ◽  
Author(s):  
G T Budd ◽  
S Green ◽  
R M O'Bryan ◽  
S Martino ◽  
M D Abeloff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Hormone Receptor ◽  
Disease Free Survival ◽  
Free Survival ◽  
Node Positive ◽  
Short Course ◽  
Disease Free ◽  
Positive Breast Cancer

PURPOSE To compare 1 year of therapy with continuous cyclophosphamide, methotrexate, fluorouracil (5-FU), vincristine, and prednisone (CMFVP) with a short course of treatment with a doxorubicin-based regimen in the postsurgical adjuvant treatment of patients with hormone receptor-negative, node-positive breast cancer. PATIENTS AND METHODS Five-hundred thirty-one eligible women with hormone receptor-negative, node-positive breast cancer were randomized to receive either 1 year of therapy with CMFVP or 20 weeks of therapy with four 5-week courses of treatment with 5-FU, doxorubicin, cyclophosphamide, and methotrexate (FAC-M). RESULTS At a median follow-up time of 4.9 years, the two treatment arms cannot be demonstrated to be different with respect to overall survival (stratified log-rank, P = .27). The 5-year survival rate is 64% on the CMFVP arm and 61% on the FAC-M arm. CMFVP produces marginally superior disease-free survival (P = .06). The estimated 5-year disease-free survival rate is 55% for patients treated with CMFVP as opposed to 50% for patients treated with FAC-M. CONCLUSION Neither regimen was shown to be superior in terms of overall survival. Because the disease-free survival produced by CMFVP is marginally superior to that produced by FAC-M, we do not recommend FAC-M for further investigation or for routine use. Possible implications of this study are discussed in the context of other adjuvant chemotherapy trials.

Sequential Adjuvant Epirubicin-Based and Docetaxel Chemotherapy for Node-Positive Breast Cancer Patients: The FNCLCC PACS 01 Trial

2006 ◽  
Vol 24 (36) ◽  
pp. 5664-5671 ◽  
Author(s):  
Henri Roché ◽  
Pierre Fumoleau ◽  
Marc Spielmann ◽  
Jean-Luc Canon ◽  
Thierry Delozier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Relative Risk ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Risk Of Death ◽  
Node Positive ◽  
Disease Free ◽  
Positive Breast Cancer

Purpose The PACS 01 trial compared six cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) with a sequential regimen of three cycles of FEC followed by three cycles of docetaxel (FEC-D) as adjuvant treatment for women with node-positive early breast cancer. Patients and Methods Between June 1997 and March 2000, 1,999 patients with operable node-positive breast cancer were randomly assigned to either FEC every 21 days for six cycles, or three cycles of FEC followed by three cycles of docetaxel, both given every 21 days. Hormone-receptor–positive patients received tamoxifen for 5 years after chemotherapy. The primary end point was 5-year disease-free survival (DFS). Results Median follow-up was 60 months. Five-year DFS rates were 73.2% with FEC and 78.4% with FEC-D (unadjusted P = .011; adjusted P = .012). Multivariate analysis adjusted for prognostic factors showed an 18% reduction in the relative risk of relapse with FEC-D. Five-year overall survival rates were 86.7% with FEC and 90.7% with FEC-D, demonstrating a 27% reduction in the relative risk of death (unadjusted P = .014; adjusted P = .017). The incidence of grade 3 to 4 neutropenia, the need for hematopoietic growth factor, and incidence of nausea/vomiting were higher with FEC. Docetaxel was associated with more febrile neutropenia in the fourth cycle, stomatitis, edema, and nail disorders. Though rare overall, there were fewer cardiac events after FEC-D (P = .03), attributable mainly to the lower anthracycline cumulative dose. Conclusion Sequential adjuvant chemotherapy with FEC followed by docetaxel significantly improves disease-free and overall survival in node-positive breast cancer patients and has a favorable safety profile.

Sign in / Sign up

Export Citation Format

Share Document