Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early Breast Cancer: Results From the GEICAM/2003-10 Study

2015 ◽  
Vol 33 (32) ◽  
pp. 3788-3795 ◽  
Author(s):  
Miguel Martín ◽  
Amparo Ruiz Simón ◽  
Manuel Ruiz Borrego ◽  
Nuria Ribelles ◽  
Álvaro Rodríguez-Lescure ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Invasive Disease ◽  
Hazard Ratio ◽  
Free Survival ◽  
Node Positive ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Disease Free

Purpose Capecitabine is an active drug in metastatic breast cancer (BC). GEICAM/2003-10 is an adjuvant trial to investigate the integration of capecitabine into a regimen of epirubicin and docetaxel for node-positive early BC. Patients and Methods Patients with operable node-positive BC (T1-3/N1-3) were eligible. After surgery, 1,384 patients were randomly assigned to receive epirubicin plus cyclophosphamide (EC; 90 and 600 mg/m2, respectively, × four cycles), followed by docetaxel (100 mg/m2 × four cycles; EC-T) or epirubicin plus docetaxel (ET; 90 and 75 mg/m2, respectively, × four cycles), followed by capecitabine (1,250 mg/m2 twice a day on days 1 to 14, × four cycles; ET-X); all regimens were given every 3 weeks. The primary end point was invasive disease-free survival. Secondary end points included safety (with an alopecia-specific study) and overall survival (OS). Results After a median follow-up of 6.6 years and 297 events, 86% of patients who received EC-T and 82% of those who received ET-X were invasive disease free at 5 years (hazard ratio, 1.30; 95% CI, 1.03 to 1.64; log-rank P = .03). The OS difference between arms was not statistically significant (hazard ratio, 1.13; 95% CI, 0.82 to 1.55; log-rank P = .46). The most frequent grade 3 to 4 adverse events in the EC-T versus ET-X arms were neutropenia (19% v 10%), with 7% febrile neutropenia across arms; fatigue (13% v 11%); diarrhea (3% v 11%); hand-foot syndrome (2% v 20%); mucositis (6% v 5%); vomiting (both, 5%); and myalgia (4.5% v 1%). Incomplete scalp hair recovery was more frequent in the EC-T than ET-X arm (30% v 14%), and patients who received EC-T wore wigs significantly longer than those who received ET-X (8.35 v 6.03 months). Conclusion Invasive disease-free survival, but not OS, was significantly superior for patients with node-positive early BC who received the adjuvant standard schedule EC-T than for those who received the experimental ET-X regimen. Toxicity profiles differed substantially across arms.

Invasive disease-free survival benefit following neratinib as extended adjuvant therapy in centrally-confirmed HER2+ early-stage breast cancer: The ExteNET phase III randomized placebo-controlled trial.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 117-117 ◽  
Author(s):  
Arlene Chan ◽  
Miguel Martin ◽  
Gunter Von Minckwitz ◽  
Bent Ejlertsen ◽  
Stephen K. L. Chia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Invasive Disease ◽  
Phase Iii ◽  
Free Survival ◽  
Disease Free

117 Background: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor with clinical efficacy in trastuzumab pre-treated HER2-positive (HER2+) metastatic breast cancer (BC). ExteNET is an ongoing multicenter randomized placebo-controlled phase III trial evaluating the efficacy and safety of a 1-year course of neratinib in patients with early-stage HER2+ BC after trastuzumab-based adjuvant therapy (clinicaltrials.gov: NCT00878709). Methods: Women with locally-confirmed early-stage HER2+ BC were randomly assigned to oral neratinib 240mg/day or matching placebo for 1 year. Archived diagnostic tumor samples were submitted for HER2 gene amplification testing at a central laboratory. Primary endpoint: invasive disease-free survival (iDFS). Secondary endpoints: DFS including ductal carcinoma in situ (DFS+DCIS); distant disease-free survival (DDFS); time to distant recurrence (TDR). Stratified Cox proportional-hazards models were used to estimate hazard ratios (HR) for the ITT and amended ITT (aITT) populations; unstratified models were used for the centrally confirmed HER2 population. Treatment groups were compared using 2-sided log-rank tests. Results: The ITT population included 2840 patients (neratinib, N=1420; placebo, N=1420). The higher-risk aITT population (i.e. node-positive disease and randomized ≤1 year of completing prior trastuzumab) included 1873 patients (neratinib, N=938; placebo, N=935). Of the tumor samples analyzed, 1463 (86%) were centrally confirmed (neratinib, N=741; placebo, N=722). Conclusions: Neratinib significantly improves iDFS in trastuzumab-treated early-stage HER2+ BC patients. An enhanced treatment effect is observed with neratinib in women with centrally confirmed HER2+ tumors. Clinical trial information: NCT00878709. [Table: see text]

scholarly journals Concurrent Doxorubicin Plus Docetaxel Is Not More Effective Than Concurrent Doxorubicin Plus Cyclophosphamide in Operable Breast Cancer With 0 to 3 Positive Axillary Nodes: North American Breast Cancer Intergroup Trial E 2197

2008 ◽  
Vol 26 (25) ◽  
pp. 4092-4099 ◽  
Author(s):  
Lori J. Goldstein ◽  
Anne O'Neill ◽  
Joseph A. Sparano ◽  
Edith A. Perez ◽  
Lawrence N. Shulman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Operable Breast Cancer ◽  
Free Survival ◽  
Significant Difference ◽  
Negative Tumor ◽  
Grade 3 ◽  
Disease Free

PurposeThe combination of doxorubicin and cyclophosphamide (AC) is a standard adjuvant regimen. Doxorubicin and docetaxel (AT) is one of the most active cytotoxic regimens for metastatic breast cancer. The purpose of this trial was to determine whether adjuvant AT improved disease-free survival compared with AC in operable breast cancer.Patients and MethodsWomen with invasive breast cancer were eligible if there were one to three positive lymph nodes or if the node-negative tumor was greater than 1 cm. Patients were randomly assigned after surgery to receive doxorubicin (60 mg/m2) plus either cyclophosphamide (600 mg/m2; AC) or docetaxel (60 mg/m2; AT) given every 3 weeks for four cycles, followed by hormone therapy for patients with estrogen receptor (ER) and/or progesterone receptor (PR)–positive tumors.ResultsThere were 2,882 eligible patients enrolled. After a median follow-up of 79.5 months, there was no significant difference in disease-free survival (DFS; 85% in both arms) or overall survival (91% v 92%) at 5 years. The hazard ratio for AC versus AT was 1.02 (95% CI for DFS, 0.86 to 1.22; P = .78). In an exploratory analysis of prespecified stratification factors by ER and PR expression there were trends toward improved DFS for AT in ER/PR-negative disease. Grade 3 neutropenia associated with fever or infection occurred more often with AT (26% v 10%; P < .05).ConclusionAT did not improve DFS or overall survival in this population, and was associated with more toxicity.

Is It The Time That We Can Depend on Bioscore as a New Staging System in Non-Metastatic Breast Cancer to Predict the Disease-Free Survival?

2021 ◽  
Author(s):  
Rehab Farouk Mohamed ◽  
Donia Hussein Abd El Hameed ◽  
Mohamed Alaa Eldeen Hassan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Free Survival ◽  
Disease Free

Abstract Purpose: Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value. This study investigates the prognostic value of the Bioscore among non-metastatic breast cancer patients with respect to disease free survival (DFS).Methods: This study included 317 patients with non-metastatic surgically treated breast cancer; they were identified in the period from January 2015 to December 2018 at Clinical Oncology Department of Assiut University Hospital. Many variables were used; pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptors (PR), and human epidermal growth factor receptor (HER2) status. Univariate & two multivariate analyses were performed to identify which of these variables are associated with disease-free survival (DFS). Results: The only significant factors in the Univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER -ve, PR -ve, and HER2 –ve. The factors which were significant in the first multivariate analysis; PS3, G3, ER –ve, and in the second one were; T2, T4, N3, G3, and ER –ve. Two sets of models were built to determine the utility of combining variables. Models incorporating G and E status had the highest C-index (0.72) for T+N + G + ER in comparison with (0.69) for (PS+ G + ER) and the lowest AIC (953.01) for T + N + G + E and (966.9) for PS + G + E. Conclusions: This study confirms the prognostic significance of bioscore in non-metastatic breast cancer in concerning DFS.

scholarly journals Stem Cells Inhibition by Bevacizumab in Combination with Neoadjuvant Chemotherapy for Breast Cancer

2019 ◽  
Vol 8 (5) ◽  
pp. 612 ◽  
Author(s):  
Renaud Sabatier ◽  
Emmanuelle Charafe-Jauffret ◽  
Jean-Yves Pierga ◽  
Hervé Curé ◽  
Eric Lambaudie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Cells ◽  
Disease Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Open Label ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free

Preclinical works have suggested cytotoxic chemotherapies may increase the number of cancer stem cells (CSC) whereas angiogenesis inhibition may decrease CSC proliferation. We developed a proof of concept clinical trial to explore bevacizumab activity on breast CSC. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicenter phase II trial. All received FEC-docetaxel combination, and patients randomized in the experimental arm received concomitant bevacizumab. The primary endpoint was to describe ALDH1 (Aldehyde dehydrogenase 1) positive tumor cells rate before treatment and after the fourth cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Seventy-five patients were included. ALDH1+ cells rate increase was below the predefined 5% threshold in both arms for the 32 patients with two time points available. Grade 3 or 4 adverse events rates were similar in both arms. A non-significant increase in pCR was observed in the bevacizumab arm (42.6% vs. 18.2%, p = 0.06), but survival was not improved (OS: p = 0.89; DFS: p = 0.45; and RFS: p = 0.68). The increase of ALDH1+ tumor cells rate after bevacizumab-based chemotherapy was less than 5%. However, as similar results were observed with chemotherapy alone, bevacizumab impact on breast CSC cells cannot be confirmed.

scholarly journals Rationale and description of a lifestyle intervention programme to achieve moderate weight loss in women with non-metastatic breast cancer: the lifestyle intervention part of the SUCCESS C Study

2020 ◽  
pp. bmjnph-2020-000119
Author(s):  
Dagmar Hauner ◽  
Brigitte Rack ◽  
Thomas Friedl ◽  
Philip Hepp ◽  
Wolfgang Janni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Weight Loss ◽  
Lifestyle Intervention ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Intervention Programme ◽  
Long Term Outcome ◽  
Free Survival ◽  
Disease Free

ObjectiveThere is growing evidence from observational studies that lifestyle factors such as obesity, an unhealthy diet and lack of physical activity are associated with poor long-term outcome in women with breast cancer. The primary objective of the lifestyle modification part of the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS C) Trial is to investigate the effect of an individualised lifestyle intervention programme aiming at moderate weight loss on disease-free survival in women with HER2/neu-negative breast cancer. Secondary objectives include the effect of the intervention on body weight, cardiovascular risk and quality of life.MethodsThe SUCCESS C Trial is an open-label, multicentre, randomised controlled phase III study using a 2×2 factorial design in women with newly diagnosed HER2/neu-negative intermediate-risk to high-risk breast cancer. The first randomisation served to compare disease-free survival in patients treated with two different chemotherapy regimens (3642 participants). The second randomisation served to compare disease-free survival in patients with a body mass index of 24–40 kg/m² (2292 participants) receiving either a telephone-based individualised lifestyle intervention programme for moderate weight loss or general recommendations for a healthy lifestyle for 2 years. Outcome analyses will be conducted after 5 years of follow-up.PerspectiveThis study will provide information on the efficacy and safety of a comprehensive lifestyle intervention programme on disease-free survival in a large cohort of women with breast cancer. EU Clinical Trials Identifier: 2008-005453-38.

scholarly journals Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 423-430 ◽  
Author(s):  
Alberto Zambelli ◽  
Giovanni Pappagallo ◽  
Paolo Marchetti
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Disease Free

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

Prognostic Role of Estrogen Receptor Determination in Breast Cancer

1983 ◽  
Vol 69 (6) ◽  
pp. 527-530 ◽  
Author(s):  
Stefano Ciatto ◽  
Patrizia Bravetti ◽  
Gaetano Cardona ◽  
Luigi Cataliotti ◽  
Roberto Crescioli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recent Literature ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Prognostic Role ◽  
Free Survival ◽  
The Difference ◽  
Disease Free ◽  
Actuarial Method

The authors report on 283 primary, non-metastatic, breast cancer cases consecutively referred after surgery and followed-up from a minimum of 10 months to a maximum of 3.5 years. All cases were studied according to the presence of estrogen receptors (ER). ER presence was correlated with age and menstrual status, with ER+ cases more frequent in older patients. No correlation was found between ER and nodal status. Prognosis was evaluated in terms of disease-free survival at 2 years (actuarial method). No correlation between ER and survival was evident for N– cases, whereas a better prognosis was recorded for ER+N+ patients compared to ER-N+, although the difference was not statistically significant. The observed results are compared with recent literature data and agree with other recent reports, which did not confirm the previously undiscussed statement regarding the prognostic role of ER determination. According to these studies and to the present study, the prognostic role of ER determination seems at least questionable and particularly the postoperative adjuvant treatment of ER-N– cases should be reconsidered.

Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in operable breast cancer: Results of Intergroup Trial E1199

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 516-516 ◽  
Author(s):  
J. A. Sparano ◽  
M. Wang ◽  
S. Martino ◽  
V. Jones ◽  
E. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Axillary Lymph ◽  
Free Survival ◽  
Significant Difference ◽  
Phase Iii Study ◽  
Grade 3

516 Background: Evidence suggests that docetaxel is more effective than paclitaxel, and paclitaxel is more effective when given weekly than every 3 weeks in metastatic breast cancer (BC). Methods: Eligibility included axillary lymph node positive or high-risk (tumor at least 2 cm) node-negative BC. All patients received 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks × 4 (P3), (2) paclitaxel 80 mg/m2 weekly × 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks × 4 (D3), or (4) docetaxel 35 mg/m2 weekly × 12 (D1). The primary comparisons included taxane (P vs. D) and schedule (every 3 weeks vs. weekly), and secondary comparisons included P3 vs. other arms. The trial had 86% power to detect a 17.5% decrease in disease-free survival (DFS) for either primary comparison, and 80% power to detect a 22% decrease for the secondary comparisons (2-sided nomimal 5% level tests corrected for multiple comparisons). Results: A total of 4,950 eligible patients were accrued. There was no difference in the primary comparisons afer 856 DFS events and 483 deaths after a median follow-up of 46.5 months at the 4th interim analysis ( www.sabcs.org , abstract 48). This is the final pre-specified analysis for the primary comparisons after 1,042 DFS events and 650 deaths (with 1,020 DFS events at this time, to be updated at the meeting). After a median followup of 60.2 months, there remains no significant difference in the hazard ratio (HR) for the taxane (1.02; p=0.73) or schedule (1.07; p=0.30) (as in the first analysis). In secondary comparisons of the standard arm (P3) with the other arms (HR > 1 favoring the experimental arms), the HRs were 1.30 (p = 0.003) for arm P1, 1.24 (p=0.02) for arm D3, and 1.09 (p=0.33) for arm D1. Analysis of interaction by hormone-receptor status will be presented. The incidence of worst grade toxicity (grade 3/4) was 24%/6% for arm P3, 24%/3% for arm P1, 21%/50% for arm D3, and 38%/6% for arm D1. Conclusions: There were no differences in DFS when comparing taxane or schedule overall. DFS was significantly improved in the weekly paclitaxel and every 3-week docetaxel arms compared with the every 3-week paclitaxel arm. [Table: see text]

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