Phase III Trial of Concurrent or Sequential Adjuvant Chemoradiotherapy After Conservative Surgery for Early-Stage Breast Cancer: Final Results of the ARCOSEIN Trial

2007 ◽  
Vol 25 (4) ◽  
pp. 405-410 ◽  
Author(s):  
Alain Toledano ◽  
David Azria ◽  
Pascal Garaud ◽  
Alain Fourquet ◽  
Daniel Serin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locoregional Recurrence ◽  
Early Stage ◽  
Treatment Protocol ◽  
Disease Free Survival ◽  
New Drugs ◽  
Phase Iii ◽  
Adjuvant Chemoradiotherapy ◽  
Free Survival ◽  
Significant Difference

Purpose In 1996, we initiated the French multicenter phase III randomized trial to compare the effect on disease-free survival (DFS) of concurrent versus sequential chemotherapy (CT) and radiotherapy (RT) after breast-conserving surgery for stages I and II breast cancer. This report presents the clinical results with a median follow-up of 60 months. Patients and Methods Between February 1996 and April 2000, 716 patients were entered onto this trial. Adjuvant treatment began within 6 weeks after surgery. Sequential treatment of CT administered first followed by RT was compared with concurrent treatment of CT administered with RT. The CT regimen consisted of mitoxantrone (12 mg/m2), fluorouracil (500 mg/m2), and cyclophosphamide (500 mg/m2) on day 1, and it was repeated every 21 days for six courses. RT was delivered to the breast and, when indicated, to the regional lymphatics. Results There was no statistically significant difference in treatment in the 5-year DFS (80% in both groups; P = .83), locoregional recurrence-free survival (LRFS; 92% in sequential v 95% in concurrent; P = .76), metastasis-free survival (87% in sequential v 84% in concurrent; P = .55), or overall survival (90% in sequential v 91% in concurrent; P = .76). Nevertheless, in the node-positive subgroup, the 5-year LRFS was statistically better in the concurrent arm (97% in concurrent v 91% in sequential; P = .02), corresponding to a risk of locoregional recurrence decreased by 39% (hazard ratio, 0.61; 95% CI, 0.38 to 0.93). Conclusion This treatment protocol remains an appealing clinical option for many women with operable breast cancer at a high risk of recurrence. Combination treatments with new drugs for breast cancer are warranted.

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]

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 SWOG S0221: A Phase III Trial Comparing Chemotherapy Schedules in High-Risk Early-Stage Breast Cancer

2015 ◽  
Vol 33 (1) ◽  
pp. 58-64 ◽  
Author(s):  
George T. Budd ◽  
William E. Barlow ◽  
Halle C.F. Moore ◽  
Timothy J. Hobday ◽  
James A. Stewart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Hormone Receptor ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Secondary Outcome ◽  
Original Design ◽  
Significant Difference

Purpose To determine the optimal dose and schedule of anthracycline and taxane administration as adjuvant therapy for early-stage breast cancer. Patients and Methods A 2 × 2 factorial design was used to test two hypotheses: (1) that a novel continuous schedule of doxorubicin-cyclophosphamide was superior to six cycles of doxorubicin-cyclophosphamide once every 2 weeks and (2) that paclitaxel once per week was superior to six cycles of paclitaxel once every 2 weeks in patients with node-positive or high-risk node-negative early-stage breast cancer. With 3,250 patients, a disease-free survival (DFS) hazard ratio of 0.82 for each randomization could be detected with 90% power with two-sided α = .05. Overall survival (OS) was a secondary outcome. Results Interim analyses crossed the futility boundaries for demonstrating superiority of both once-per-week regimens and once-every-2-weeks regimens. After a median follow-up of 6 years, a significant interaction developed between the two randomization factors (DFS P = .024; OS P = .010) in the 2,716 patients randomly assigned in the original design, which precluded interpretation of the two factors separately. Comparing all four arms showed a significant difference in OS (P = .040) but not in DFS (P = .11), with all treatments given once every 2 weeks associated with the highest OS. This difference in OS seemed confined to patients with hormone receptor–negative/human epidermal growth factor receptor 2 (HER2) –negative tumors (P = .067), with no differences seen with hormone receptor–positive/HER2-negative (P = .90) or HER2-positive tumors (P = .40). Conclusion Patients achieved a similar DFS with any of these regimens. Subset analysis suggests the hypothesis that once-every-2-weeks dosing may be best for patients with hormone receptor–negative/HER2-negative tumors.

Taxane-based adjuvant chemotherapy in node positive, early stage Turkish breast cancer patients

Open Medicine ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. 454-458
Author(s):  
Ahmet Alacacioglu ◽  
Baha Zengel ◽  
Ali Denecli
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Early Stage ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Node Positive ◽  
Significant Difference ◽  
Disease Free

AbstractAdjuvant chemotherapy decreases the risk of breast cancer recurrence in patients with breast cancer. In addition, it increases the rate of survival. Therefore, various chemotherapy regimens are administered in the treatment of breast cancer. The efficacy of taxane-based adjuvant chemotherapies has been demonstrated in various trials. This trial was designed to retrospectively evaluate the efficacy of taxane-based chemotherapies in lymph node-positive, early-stage Turkish breast cancer patients. 29 patients receiving TAC regimen and 29 patients receiving AC+P regimen were evaluated. 6 courses of TAC regimen were administered every 3 weeks (docetaxel 75 mg/m2, doxorubicine 50 mg/m2, cyclophosphamide 500 mg/m2). The other patient group was administered AC+P regimen (4 courses of doxorubicin 60mg/m2, cyclophosphamide 600 mg/m2 combination every 2 weeks, followed by paclitaxel 175 mg/m2 for 4 courses every 2 weeks). The 1-year, 2-year and 3-year disease-free survival (DFS) rates were 96.3%, 81.1% and 72.8% respectively. No significant difference was detected in DFS between premenopausal and postmenopausal patients on the taxane regimen (p=0.82). There was no significant difference in DFS between estrogen or progesterone receptor positive and negative patients (p=0.46). Disease-free survival of patients receiving TAC and AC+P adjuvant chemotherapy regimen was compared. The follow-up period of patients on AC+P chemotherapy was longer than those receiving TAC (AC+P mean 38.6±12.8 months, TAC mean 17.1±5.4 months). No significant difference was observed upon evaluation of both treatment arms with respect to DFS (p=0.92). In conclusion, this trial once more demonstrated that taxane-based adjuvant chemotherapy was effective and safe in lymph node-positive, early-stage Turkish breast cancer patients.

Denosumab versus placebo as adjuvant treatment for women with early-stage breast cancer who are at high risk of disease recurrence (D-CARE): An international, randomized, double-blind, placebo-controlled phase III clinical trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS670-TPS670
Author(s):  
Paul Edward Goss ◽  
Carlos H. Barrios ◽  
Richard Bell ◽  
Dianne M Finkelstein ◽  
Hiroji Iwata ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Stage ◽  
Human Monoclonal Antibody ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Free Survival ◽  
Oral Bisphosphonate ◽  
Her 2

TPS670 Background: Bone is a common site of distant recurrence in women with early-stage breast cancer, and represents approximately 40% of all first recurrences. Tumor cells in bone release growth factors and cytokines that stimulate osteoclast-mediated bone resorption through the RANK ligand (RANKL) pathway. In preclinical studies, RANKL inhibition significantly delays skeletal tumor formation, reduces skeletal tumor burden, and prolongs survival of tumor-bearing mice. Denosumab is a fully human monoclonal antibody that binds to RANKL with high affinity and specificity. It is approved for the prevention of skeletal-related events in patients with established bone metastases from a variety of solid tumors. The purpose of the D-CARE trial is to evaluate the ability of denosumab to prolong bone metastasis-free survival (BMFS) and disease-free survival (DFS) in the adjuvant breast cancer setting. Methods: Approximately 4,500 women with stage II or III breast cancer, at high risk for recurrence and with known hormone and HER-2 receptor status, are eligible. Standard-of-care adjuvant or neoadjuvant chemo-, endocrine, or HER-2 targeted therapy, alone or in combination must be planned. Exclusion criteria include: a prior history of breast cancer (except DCIS or LCIS) or distant metastasis, oral bisphosphonate (BP) use within 1 year of randomization or any intravenous BP use. Patients are randomized 1:1 to receive denosumab 120 mg or placebo subcutaneously monthly for 6 months, then every 3 months for a total of 5 years of treatment. All patients receive vitamin D (≥ 400 IU) and calcium (≥ 500 mg) supplements. Primary endpoint of this event-driven trial is BMFS. Secondary endpoints include DFS and overall survival. Safety, quality of life assessments, breast density, and biomarkers are additional endpoints. The trial, sponsored by Amgen Inc. and registered with the ClinicalTrials.gov identifier NCT01077154, began enrolling patients in June 2010 and is expected to complete in October 2016. Paul Goss and Dianne Finkelstein supported in part by the Avon Foundation New York.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

scholarly journals Relationship between Ribosomal Protein S6-pS240 Expression and other Prognostic Factors in Non-Special Type Invasive Breast Cancer

Breast Care ◽  
2018 ◽  
Vol 14 (3) ◽  
pp. 171-175
Author(s):  
Frederik Cuperjani ◽  
Lumturije Gashi ◽  
Fisnik Kurshumliu ◽  
Shemsedin Dreshaj ◽  
Fitim Selimi
Keyword(s):  
Breast Cancer ◽  
Ribosomal Protein ◽  
Invasive Breast Cancer ◽  
Menopausal Status ◽  
Treatment Protocol ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free

Background: The aim of this study was to investigate the immunohistochemical expression of ribosomal protein (RP) S6-pS240 in non-special type invasive breast cancer in relation to other prognostic markers and gain new insights to facilitate more individualized treatment. Methods: The following clinical and histopathological parameters of 120 patients were determined: S6-pS240 expression, age, menopausal status, tumor size and grade, TNM stage, Nottingham Prognostic Index (NPI), lymph node stage, estrogen and progesterone receptor (ER/PR) expression, HER2/neu amplification, lymphovascular invasion, and proliferative index as measured by Ki-67. Treatment protocol and disease-free survival were evaluated accordingly. Results: Significant positive correlations were seen between S6-pS240 expression and Ki-67 values (rho = 0.530, p < 0.001), and NPI (rho = 0.370, p < 0.001) and HER2/neu amplification (rho = 0.368, p < 0.001). A negative correlation was found between S6-pS240 and ER/PR expression (rho = 0.362, p < 0.001). Patients with negative RP S6-pS240 expression had significantly longer disease-free survival (log-rank test, p = 0.005). Conclusion: Immunohistochemical analysis of RP S6-pS240 is a valuable additional prognostic marker in patients with invasive breast cancer. Routine use of S6-pS240 immunohistochemistry is recommended.

Sign in / Sign up

Export Citation Format

Share Document