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.

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.

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 Real-world adjuvant TAC or FEC-D for HER2-negative node-positive breast cancer in women less than 50 years of age

2016 ◽  
Vol 23 (3) ◽  
pp. 164 ◽  
Author(s):  
S. Lupichuk ◽  
D. Tilley ◽  
X. Kostaras ◽  
A.A. Joy
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Granulocyte Colony Stimulating Factor ◽  
Free Survival ◽  
Node Positive ◽  
Patient Groups ◽  
Stimulating Factor ◽  
Disease Free ◽  
Positive Breast Cancer

Purpose We compared the efficacy, toxicity, and use of granulocyte colony–stimulating factor (G-CSF) with TAC (docetaxel–doxorubicin–cyclophosphamide) and FEC-D (5-fluorouracil–epirubicin–cyclophosphamide followed by docetaxel) in women less than 50 years of age.Methods The study included all women more than 18 years but less than 50 years of age with her2-negative, node-positive, stage II or III breast cancer diagnosed in Alberta between 2008 and 2012 who received TAC (n = 198) or FEC-D (n = 274).Results The patient groups were well-balanced, except that radiotherapy use was higher in the TAC group (91.9% vs. 79.9%, p < 0.001). At a median follow-up of 49.6 months, disease-free survival was 91.4% for TAC and 92.0% for FEC-D (p = 0.76). Overall survival (OS) was 96% with TAC and 95.3% with FEC-D (p = 0.86).The incidences of grades 3 and 4 toxicities were similar in the two groups (all p > 0.05). Overall, febrile neutropenia (FN) was reported in 11.6% of TAC patients and 15.7% of FEC-D patients (p = 0.26). However, use of G-CSF was higher in the TAC group than in the FEC-D group (96.4% vs. 71.5%, p < 0.001). Hospitalization for FN was required in 10.5% of TAC patients and 13.0% of FEC-D patients (p = 0.41). In G-CSF–supported and –unsupported patients receiving tac, FN occurred at rates of 11.1% and 33.3% respectively (p = 0.08); in patients receiving the FEC portion of FEC-D, those proportions were 2.9% and 8.1% respectively (p = 0.24); and in patients receiving docetaxel after FEC, the proportions were 4.1% and 17.6% respectively (p < 0.001).Conclusions In women less than 50 years of age receiving adjuvant TAC or FEC-D, we observed no differences in efficacy or other nonhematologic toxicities. Based on the timing and rates of FN, use of prophylactic G-CSF should be routine for the docetaxel-containing portion of treatment; however, prophylactic G-CSF could potentially be avoided during the FEC portion of FEC-D treatment.

Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Beata Jagielska ◽  
Andrzej Czubek ◽  
Konrad Tałasiewicz ◽  
A. Twarowski ◽  
P. Rutkowski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Statistical Analysis ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Clinical Staging ◽  
Primary Tumors ◽  
Free Survival ◽  
Adjuvant Immunotherapy ◽  
Disease Free

Introduction In patients suffering from breast cancer, adjuvant radiation, chemotherapy, or immunotherapy, which immediately follow the surgery as the first line therapy, greatly improve overall (OS) and disease-free survival (DFS). Various regimens of adjuvant therapy for these patients have been tested contingent upon the clinical staging. Inclusion of adjuvant immunotherapy is particularly promising. Specific aim The aim of this study was to assess efficacy of trastuzumab (Herceptin) - comprising adjuvant immunotherapy in terms of overall and disease-free survival as compared to other adjuvant therapies. Patients All patients were presented with the Patient Bill of Rights and have provided the Patient Informed Consent to participate in this study. Eligible patients include those with primary tumors initially staged at the clinical stages: I-T1c N0, II-T0-2, N0-1, or IIIA-T3 N1, or patients for whom neoadjuvant chemotherapy provides the possibility to remove surgically a tumor at the stage IIIA T0-3 N2. Of 9,058 patients enrolled in the Breast Cancer Treatment Program between 2008 and 2015, 6,832 fulfilled the inclusion criteria. Statistical Analysis The effects of clinical and demographic factors on overall survival (OS) and disease-free survival (DFS) were assessed using Cox’s proportional hazards regression models. OS and DFS were evaluated with Kaplan-Meier calculations. The study was meeting the criteria for a controlled, open-access clinical trial. Results OS rates for years 1-7 were, respectively, 99.42%, 97.26%, 94.57%, 92.41%, 90.48%, 88.63%, and 88.23%; thus with the 5-year survival at 90.48%. The corresponding data for DFS were 96.17%, 84.07%, 77.26%, 72.57%, 68.59%, 65.04%, and 63.05%, respectively; thus with the 5-year DFS at 68.59%. Adverse effects, with the exception of cardiac complications, occurred in 1194 (17%), while causing withdrawal of 421 (6%) patients. Most of other adverse events were related to hepatotoxicity 1755 (25%) and fatigue 681 (9.7%). Conclusion These results demonstrate the great benefits of inclusion of immunotherapy as the adjuvant component as currently the best overall therapeutic strategy for the patients suffering breast cancers. As this strategy greatly exceeds any other therapeutic options available for practicing oncologists at the present time, it definitely justifies allocation of all needed public resources, while assuring highest quality health service for the patients in Poland.

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]

Disease-free Survival of Node-positive Breast Cancer Patients

1995 ◽  
Vol 191 (10) ◽  
pp. 982-990 ◽  
Author(s):  
M. Aubele ◽  
G. Auer ◽  
A. Voss ◽  
U. Falkmer ◽  
L. Rutquist ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Node Positive ◽  
Disease Free ◽  
Positive Breast Cancer
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