Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer

2003 ◽  
Vol 21 (6) ◽  
pp. 976-983 ◽  
Author(s):  
I. Craig Henderson ◽  
Donald A. Berry ◽  
George D. Demetri ◽  
Constance T. Cirrincione ◽  
Lori J. Goldstein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Estrogen Receptor ◽  
Adjuvant Chemotherapy ◽  
Confidence Interval ◽  
Chemotherapy Regimen ◽  
Disease Free Survival ◽  
Free Survival ◽  
Adjuvant Chemotherapy Regimen ◽  
Disease Free

Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival. Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m2, with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m2, for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m2. Tamoxifen was given to 94% of patients with hormone receptor–positive tumors. Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m2, respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald χ2 P = .0023; unadjusted Wilcoxon P = .0011) and 18% for death (adjusted P = .0064; unadjusted P = .0098). At 5 years, the disease-free survival (± SE) was 65% (± 1) and 70% (± 1), and overall survival was 77% (± 1) and 80% (± 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor–negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor–positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest. Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.

5-Year Results of Dose-Intensive Sequential Adjuvant Chemotherapy for Women With High-Risk Node-Positive Breast Cancer: A Phase II Study

1999 ◽  
Vol 17 (4) ◽  
pp. 1118-1118 ◽  
Author(s):  
C. Hudis ◽  
M. Fornier ◽  
L. Riccio ◽  
D. Lebwohl ◽  
J. Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Pilot Study ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Free Survival ◽  
Dose Dense ◽  
Disease Free

PURPOSE: We conducted a phase II pilot study of dose-intensive adjuvant chemotherapy with doxorubicin followed sequentially by high-dose cyclophosphamide to determine the safety and feasibility of this dose-dense treatment and to estimate the disease-free and overall survival in breast cancer patients with four or more involved axillary lymph nodes. PATIENTS AND METHODS: Seventy-three patients received adjuvant treatment with four cycles of doxorubicin 75 mg/m2 as an intravenous bolus every 21 days, followed by three cycles of cyclophosphamide 3,000 mg/m2 every 14 days with granulocyte colony-stimulating factor support. RESULTS: Seventy-one patients were assessable, and all but two completed all planned chemotherapy. There was no treatment-related mortality. The most common toxicity was neutropenic fever, which occurred in 39% of patients. Median disease-free survival is 66 months (95% confidence interval, 34 to 98 months), and median overall survival has not yet been reached. At 5 years of follow-up, the disease-free survival is 51.7%, and overall survival is 60.0%. There is no long-term treatment-related toxicity, and no cases of acute myelogenous leukemia or myelodysplastic syndrome have been observed. CONCLUSION: Our pilot study of doxorubicin followed by cyclophosphamide demonstrates the safety and feasibility of the sequential dose-dense plan. Long-term follow-up, although noncomparative, is promising. However, this regimen is associated with a higher incidence of toxicity (and also higher costs) than the standard dose and schedule of doxorubicin and cyclophosphamide, and therefore it should not be used as conventional therapy in the absence of demonstrated improvement of outcome. Randomized trials testing the dose-dense approach have been completed but not yet reported. Because the sequential plan can decrease overlapping toxicities, it is an appropriate platform for the addition of newer active agents, such as taxanes or monoclonal antibodies.

Estrogen Receptor Expression and Efficacy of Docetaxel-Containing Adjuvant Chemotherapy in Patients With Node-Positive Breast Cancer: Results From a Pooled Analysis

2008 ◽  
Vol 26 (16) ◽  
pp. 2636-2643 ◽  
Author(s):  
Fabrice Andre ◽  
Kristine Broglio ◽  
Henri Roche ◽  
Miguel Martin ◽  
John R. Mackey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Estrogen Receptor ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
Free Survival ◽  
Er Positive ◽  
Disease Free ◽  
Er Expression ◽  
Er Status

PurposeSeveral adjuvant chemotherapy trials suggested that cytotoxic treatment is less effective in patients with estrogen receptor (ER) –positive breast cancers. The aim of the present study was to assess the efficacy of adjuvant docetaxel and anthracycline therapy according to ER expression in two randomized clinical trials.Patients and MethodsPooled data from two randomized trials, BCIRG001 and PACS01, were examined. Hazard ratios for recurrence and survival were estimated by Cox proportional hazards models and were adjusted for clinical variables. Interaction between docetaxel and ER expression was tested.ResultsER status was available for 3,329 patients (95% of all randomly assigned patients), of whom 75% (n = 2,493) were ER positive. Docetaxel therapy was associated with a 30% reduction in the risk of death (hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.91) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.52 to 0.94) in ER-negative patients. Docetaxel therapy was associated with a 21% reduction in the risk of recurrence (HR = 0.79; 95% CI, 0.66 to 0.93) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.54 to 0.97) in ER-negative patients. The interaction between docetaxel therapy and ER status was not statistically significant for either overall survival (P = .87) or disease-free survival (P = .30). ER expression was also not predictive for docetaxel efficacy when it was analyzed as a semi-continuous variable based on percent of positive cells by immunohistochemistry (test for heterogeneity, P = .56 and .86 for overall survival and disease-free survival, respectively).ConclusionIn the pooled analysis of these two trials, docetaxel did not have a statistically significantly different effect on the risk of recurrence or death in ER-positive and ER-negative patients.

Effect of Molecular Disease Subsets on Disease-Free Survival in Randomized Adjuvant Chemotherapy Trials for Estrogen Receptor–Positive Breast Cancer

2008 ◽  
Vol 26 (28) ◽  
pp. 4679-4683 ◽  
Author(s):  
Lajos Pusztai ◽  
Kristine Broglio ◽  
Fabrice Andre ◽  
W. Fraser Symmans ◽  
Kenneth R. Hess ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Adjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Disease Free Survival ◽  
Molecular Diagnostic ◽  
Free Survival ◽  
Er Positive ◽  
Disease Free ◽  
Positive Breast Cancer

Purpose The majority of estrogen receptor (ER)–positive cancers are sensitive to endocrine therapy and may not derive much further benefit from chemotherapy, but a subset are potentially chemotherapy sensitive. Molecular diagnostic tests allow the identification of these various subsets with some accuracy. The goal of the current analysis was to examine how the proportion of cases in the various risk (recurrence score [RS]) categories of a commercially available multigene assay influences the power of randomized trials to show benefit from adjuvant chemotherapy. Methods We modeled 10-year disease-free survival (DFS) for hypothetical, two-arm clinical trials that randomly assigned patients with ER-positive breast cancer to endocrine therapy alone or endocrine therapy plus chemotherapy. We varied the proportion of patients in low, intermediate, and high RS categories and used DFS estimates for each risk group based on results from the Southwest Oncology Group 8814 study. Results The probability of observing significant improvement in DFS as a result of chemotherapy decreases as the proportion of patients in the low RS category increases. For example, if a trial is designed with 80% power and the actual proportion of low RS patients accrued to the study increases from 40% to 60%, the power drops to 63%. Conclusion Variable accrual of low RS patients into different randomized adjuvant chemotherapy trials may partly explain contradictory results in the literature. Studies can be underpowered to detect improvement with chemotherapy as a result of inclusion of too many patients with low RS. Future adjuvant studies for ER-positive breast cancer will need to consider stratifying patients by molecular subtype.

scholarly journals Six versus 12 months’ adjuvant trastuzumab in patients with HER2-positive early breast cancer: the PERSEPHONE non-inferiority RCT

2020 ◽  
Vol 24 (40) ◽  
pp. 1-190 ◽  
Author(s):  
Helena Earl ◽  
Louise Hiller ◽  
Anne-Laure Vallier ◽  
Shrushma Loi ◽  
Karen McAdam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Free Survival ◽  
Life Years ◽  
Disease Free

Background The addition of adjuvant trastuzumab to chemotherapy has significantly improved outcomes for people with human epidermal growth factor receptor 2 (HER2)-positive, early, potentially curable breast cancer. Twelve months’ trastuzumab, tested in registration trials, was adopted as standard adjuvant treatment in 2006. Subsequently, similar outcomes were demonstrated using 9 weeks of trastuzumab. Shorter durations were therefore tested for non-inferiority. Objectives To establish whether or not 6 months’ adjuvant trastuzumab is non-inferior to 12 months’ in the treatment of HER2-positive early breast cancer using a primary end point of 4-year disease-free survival. Design This was a Phase III randomised controlled non-inferiority trial. Setting The setting was 152 NHS hospitals. Participants A total of 4088 patients with HER2-positive early breast cancer who it was planned would receive both chemotherapy and trastuzumab took part. Intervention Randomisation (1 : 1) to 6 months’ or 12 months’ trastuzumab treatment. Main outcomes The primary end point was disease-free survival. The secondary end points were overall survival, cost-effectiveness and cardiac function during treatment with trastuzumab. Assuming a 4-year disease-free survival rate of 80% with 12 months’ trastuzumab, 4000 patients were required to demonstrate non-inferiority of 6 months’ trastuzumab (5% one-sided significance, 85% power), defining the non-inferiority limit as no worse than 3% below the standard arm. Costs and quality-adjusted life-years were estimated using a within-trial analysis and a lifetime decision-analytic model. Results Between 4 October 2007 and 31 July 2015, 2045 patients were randomised to 12 months’ trastuzumab and 2043 were randomised to 6 months’ trastuzumab. Sixty-nine per cent of patients had ER-positive disease; 90% received anthracyclines (49% with taxanes; 41% without taxanes); 10% received taxanes without anthracyclines; 54% received trastuzumab sequentially after chemotherapy; and 85% received adjuvant chemotherapy (58% were node negative). At 6.1 years’ median follow-up, with 389 (10%) deaths and 566 (14%) disease-free survival events, the 4-year disease-free survival rates for the 4088 patients were 89.5% (95% confidence interval 88.1% to 90.8%) in the 6-month group and 90.3% (95% confidence interval 88.9% to 91.5%) in the 12-month group (hazard ratio 1.10, 90% confidence interval 0.96 to 1.26; non-inferiority p = 0.01), demonstrating non-inferiority of 6 months’ trastuzumab. Congruent results were found for overall survival (non-inferiority p = 0.0003) and landmark analyses 6 months from starting trastuzumab [non-inferiority p = 0.03 (disease-free-survival) and p = 0.006 (overall survival)]. Six months’ trastuzumab resulted in fewer patients reporting adverse events of severe grade [365/1929 (19%) vs. 460/1935 (24%) for 12-month patients; p = 0.0003] or stopping early because of cardiotoxicity [61/1977 (3%) vs. 146/1941 (8%) for 12-month patients; p < 0.0001]. Health economic analysis showed that 6 months’ trastuzumab resulted in significantly lower lifetime costs than and similar lifetime quality-adjusted life-years to 12 months’ trastuzumab, and thus there is a high probability that 6 months’ trastuzumab is cost-effective compared with 12 months’ trastuzumab. Patient-reported experiences in the trial highlighted fatigue and aches and pains most frequently. Limitations The type of chemotherapy and timing of trastuzumab changed during the recruitment phase of the study as standard practice altered. Conclusions PERSEPHONE demonstrated that, in the treatment of HER2-positive early breast cancer, 6 months’ adjuvant trastuzumab is non-inferior to 12 months’. Six months’ treatment resulted in significantly less cardiac toxicity and fewer severe adverse events. Future work Ongoing translational work investigates patient and tumour genetic determinants of toxicity, and trastuzumab efficacy. An individual patient data meta-analysis with PHARE and other trastuzumab duration trials is planned. Trial registration Current Controlled Trials ISRCTN52968807, EudraCT 2006-007018-39 and ClinicalTrials.gov NCT00712140. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 40. See the NIHR Journals Library website for further project information.

Neoadjuvant Chemotherapy with Taxotere-Epirubicin-5-Fluorouracil (TEF) in Local-Regionally Advanced Breast Cancer: A Preliminary Report

2002 ◽  
Vol 88 (6) ◽  
pp. 474-477 ◽  
Author(s):  
Eşmen Baltali ◽  
M Kadri Altundağ ◽  
Demir Ali Onat ◽  
Osman Abbasoğlu ◽  
Yavuz Özişik ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Chemotherapy Regimen ◽  
Disease Free Survival ◽  
Advanced Breast ◽  
Free Survival ◽  
The Mean ◽  
Disease Free

Aims and background Sixty-three patients with local-regionally advanced breast cancer were treated with neoadjuvant chemotherapy consisting of docetaxel (Taxotere), epirubicin, and 5-fluorouracil (TEF). Methods and study design Preoperatively, patients received four cycles of Taxotere (80 mg/m2), epirubicin (60 mg/m2), and 5-fluorouracil (500 mg/m2), repeated every 21 days. Following completion of four cycles of chemotherapy, appropriate surgery was performed. After the surgery, patients received one cycle of the TEF chemotherapy regimen; following chemotherapy, radiotherapy was applied, and at the end two more cycles of TEF chemotherapy regimen were given. Results Sixty-three patients with locally advanced breast cancer were treated. Three patients were excluded from the study before the evaluation of response. Median age of the patients was 50 years (range, 25–77). Twenty-seven and 33 patients were premenopausal and postmenopausal, respectively. Thirty-nine patients were in stage IIIA and 21 in stage IIIB. Complete and partial responses were observed in 15 (25%) and 42 (70%) of the patients following four cycles of preoperative TEF chemotherapy regimen, respectively. Overall response was 95%, and primary lesion progressed only in 3 (5%) patients. The mean disease-free survival was 15.9 ± 6.8 (range, 3.5–28) months and the mean overall survival was 18.6 ± 7.2 (range, 5–30) months. The most frequent side effects were nausea-vomiting, mucositis, alopecia and leukopenia. Conclusions TEF therapy is a treatment with a high overall response rate and toxicities similar to other taxotere combinations. A longer follow-up of patients is necessary for the determination of disease-free survival and overall survival.

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.

Neutrophil-lymphocyte index as prognostic factor for overall survival and disease-free survival in breast cancer patients

2020 ◽  
Vol 33 (4) ◽  
pp. 137-144
Author(s):  
Guillermo Peralta-Castillo ◽  
Antonio Maffuz-Aziz ◽  
Mariana Sierra-Murguía ◽  
Sergio Rodriguez-Cuevas
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Disease Free

Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer

2021 ◽  
Author(s):  
Jie-Yu Zhou ◽  
Kang-Kang Lu ◽  
Wei-Da Fu ◽  
Hao Shi ◽  
Jun-Wei Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Discriminative Ability ◽  
Free Survival ◽  
Disease Free

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

scholarly journals Circulating Tumor Cells and Cancer Stem Cells: Clinical Implications in Nonmetastatic Breast Cancer

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40856 ◽  
Author(s):  
M. Sayed ◽  
A.M. Zahran ◽  
M.S.F. Hassan ◽  
D.O. Mohamed
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Overall Survival ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Disease Free Survival ◽  
Free Survival ◽  
The Third ◽  
Disease Free

Purpose Despite the therapeutic advances, disease recurrence remains an ever-present threat to the health and well-being of breast cancer survivors. Assessment of circulating tumor cells (CTCs) and cancer stem cells (CSCs) during and after treatment may be of value in refining treatment. Methods Three 5 mL blood samples were taken from each patient: the first, at diagnosis; the second, after completion of neoadjuvant anthracyclin-based chemotherapy; and the third, a month after surgery and completion of adjuvant radiotherapy. The absolute numbers of CTCs were identified as CD45-cytokeratin+ cells. CTCs per 5 mL of blood were determined by recording all events in the whole suspension. CSCs were identified as cytokeratin+CD44+CD24-/CD45- cells. The CSCs were expressed as a percentage of CTCs. Results Univariate analysis identified the measurements of baseline CTCs and CSCs, taken after chemotherapy and one month after the cessation of radiotherapy, as prognostic factors for both four-year disease-free survival and four-year overall survival. Multivariable analysis identified the third measurement of CSCs, taken one month after the completion of radiotherapy, as the only independent prognostic factor for the four-year disease-free survival (P < 0.002, hazard ratio [HR] = 1.231, 95% CI 1.077–1.407). The initial CTC measurement was the one factor that reached significance on multivariate analysis (P < 0.03, HR 1.969, 95% CI 1.092–3.551) for the four-year overall survival. Correlation was higher between CTC and CSC counts at diagnosis ( r = 0.654, P < 0.001) than after chemotherapy ( r = 0.317, P < 0.03), because of the more rapid decrease in the mean CTC count with chemotherapy. Conclusion The CTC count could be suitable as one of the measures for monitoring response to chemotherapy, while persistence of CSC after cessation of the treatment of nonmetastatic breast cancer, except hormonal therapy when indicated, may be a reason to consider additional therapy in the future. These findings need confirmation in larger randomized trials.

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