scholarly journals Comparison of Doxorubicin and Cyclophosphamide Versus Single-Agent Paclitaxel As Adjuvant Therapy for Breast Cancer in Women With 0 to 3 Positive Axillary Nodes: CALGB 40101 (Alliance)

2014 ◽  
Vol 32 (22) ◽  
pp. 2311-2317 ◽  
Author(s):  
Lawrence N. Shulman ◽  
Donald A. Berry ◽  
Constance T. Cirrincione ◽  
Heather P. Becker ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Duration Of Therapy ◽  
The One ◽  
Absolute Advantage

Purpose Optimal adjuvant chemotherapy for early-stage breast cancer balances efficacy and toxicity. We sought to determine whether single-agent paclitaxel (T) was inferior to doxorubicin and cyclophosphamide (AC), when each was administered for four or six cycles of therapy, and whether it offered less toxicity. Patients and Methods Patients with operable breast cancer with 0 to 3 positive nodes were enrolled onto the study to address the noninferiority of single-agent T to AC, defined as the one-sided 95% upper-bound CI (UCB) of hazard ratio (HR) of T versus AC less than 1.30 for the primary end point of relapse-free survival (RFS). As a 2 × 2 factorial design, duration of therapy was also addressed and was previously reported. Results With 3,871 patients enrolled onto the trial, a median follow-up period of 6.1 years, and 437 RFS events, we achieved an HR of 1.26 (one sided 95% UCB, 1.48; favoring AC does not allow a conclusion of noninferiority of T with AC; UCB > 1.3). With 266 patient deaths, the HR for overall survival (OS) was 1.27 favoring AC (UCB, 1.56). The estimated absolute advantage of AC at 5 years is 3% for RFS (91 v 88%) and 1% for OS (95 v 94%). All nine treatment-related deaths were patients receiving AC and are included in the analyses of both RFS and OS. Hematologic toxicity was more common in patients treated with AC, and neuropathy was more common in patients treated with T. Conclusion This trial did not show noninferiority of T to AC, a conclusion that is unlikely to change with additional events and follow-up. T was less toxic than AC.

Comparison of doxorubicin and cyclophosphamide (AC) versus single-agent paclitaxel (T) as adjuvant therapy for breast cancer in women with 0-3 positive axillary nodes: CALGB 40101.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1007-1007
Author(s):  
Lawrence N. Shulman ◽  
Donald A. Berry ◽  
Constance T. Cirrincione ◽  
Heather Becker ◽  
Edith A. Perez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Relative Effectiveness ◽  
Single Agent ◽  
Hazard Ratio ◽  
Hematologic Toxicity ◽  
Grade 3 ◽  
Reduced Toxicity ◽  
Absolute Advantage

1007 Background: Determining optimal adjuvant chemotherapy for early stage breast cancer depends on efficacy and toxicity. We sought to determine if T is equivalent to AC but with reduced toxicity. Methods: Pts with operable breast cancer with 0-3 positive nodes were enrolled on a 2x2 factorial design study which addressed (1) superiority of 6 vs. 4 cycles of therapy (previously reported, Shulman, JCO 2012) and (2) equivalence of single-agent T to standard AC, defined as upper bound of 95% confidence interval (CI) of hazard ratio (HR) of T vs. AC < 1.30 for the primary endpoint of relapse-free survival (RFS). A planned target of 567 RFS events required 4,646 pts with 4 yrs FU. At activation in 2002, T (80mg/m2) was q1wk for 12 or 18 wks and AC (60/600 mg/m2) was q3wk for 4 or 6 cycles. In 2003 (570 pts enrolled) schedules were revised to 4 or 6 cycles q2wk for both T (175 mg/m2) and AC. The 6-cycle arms were dropped in 2008 (3,171 pts enrolled) due to slow accrual. Relative effectiveness of T to AC is shown by hazard ratio (HR). Logrank p-values are measures of discordance but are not relevant for the equivalence question and are not adjusted for multiple comparisons. Results: After enrolling 3,871 pts, the study closed in 2010 due to slowing accrual. With a median follow-up of 6.1 yrs there are 437 RFS events. The HR of 1.26 (95% CI: 1.05-1.53; p = 0.02) does not allow a conclusion of equivalence of T with AC. With 266 deaths the HR for overall survival (OS) is 1.27 (95% CI=1.00-1.62; p = 0.05), favoring AC. The estimated absolute advantage of AC at 5 yrs is 3% (91 vs. 88%) for RFS and 1% (95 vs. 94%) for OS. All 9 treatment-related deaths were in pts receiving AC and are included in the survival analysis. The incidence of Grade 3+ toxicity for AC vs T was 33% vs. 4% for hematologic toxicity and 36% vs 22% for non-hematologic toxicity. Conclusions: This trial did not show equivalence of T to AC, a conclusion that is very unlikely to change with additional follow-up. T was less toxic than AC. Clinical trial information: CDR0000069444/NCT00041119.

The association of clinical-pathologic factors and Oncotype Dx recurrence score (RS) in the outcome of early stage breast cancer.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 55-55
Author(s):  
Manjeet Chadha ◽  
Robert Stewart ◽  
Jonathan Wallach
Keyword(s):  
Breast Cancer ◽  
Patient Outcomes ◽  
Early Stage ◽  
Brca Mutation ◽  
Recurrence Score ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Pathologic Features ◽  
Oncotype Dx Recurrence Score

55 Background: Oncotype Dx recurrence score (RS) is routinely used to guide systemic therapy based on the estimated risk for distant relapse. Patients with early stage disease are also at risk for locoregional recurrence, and in some instances local relapse is the only site of failure. The objective of this study is to evaluate patient outcomes in association with known clinical-pathologic risk factors and RS. Observations in context of known clinical-pathologic features and RS may have important clinical implications relative to adjuvant locoregional therapy. Methods: This is an IRB approved retrospective study that includes patients with unilateral breast cancer and in whom the RS was reported. A total of 716 patients met this defined criteria. Seventy two percent underwent breast conserving therapy (BCS) and 28% underwent mastectomy; 68% had stage I and the remaining had > Stage II disease.The clinical-pathologic variables including age, stage, BRCA mutation, extent of surgery, and RS were studied in evaluating patient outcomes. Results: The median age was 56 years (27 to 84 years). The overall distribution of RS reported as low (18), intermediate (19-30), and high ( > 31) was 59%, 31%, and 10%, respectively. This distribution ratio was no different among patients treated with BCS and mastectomy. However, among BRCA mutation carriers there was a higher incidence of the high RS.Overall, the median follow up was over 3 years, and 25% of the patients have been followed over 5 years. The 3-year and 5-year any relapse-free survival was 93% and 89%, respectively. Age was significantly associated with observed inferior any relapse-free survival; 85% and 91% in women < 40 years vs > 40 years, respectively (p = 0.018). On univariate analysis, RS had no significant association with local regional relapse free survival. Further, associations between the clinical-pathologic features and RS using multivariate analysis will be presented. Conclusions: Observations with early follow up do not suggest a select role of RS in guiding risk tailored local regional therapy. Longer follow will further our understanding of patients at risk for local regional relapse.

scholarly journals Neural Network Analysis of Follow-Up Data in Primary Breast Cancer

2000 ◽  
Vol 15 (1) ◽  
pp. 116-122 ◽  
Author(s):  
N. Harbeck ◽  
R. Kates ◽  
K Ulm ◽  
H. Graeff ◽  
M. Schmitt
Keyword(s):  
Breast Cancer ◽  
Neural Network ◽  
Risk Group ◽  
Neural Network Analysis ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Neural Network ◽  
Pai 1

This paper reports on the performance of a recently developed neural network environment incorporating likelihood-based optimization and complexity reduction techniques in the analysis of breast cancer follow-up data with the goal of building up a clinical decision support system. The inputs to the neural network include classical factors such as grading, age, tumor size, estrogen and progesterone receptor measurements, as well as tumor biological markers such as PAI-1 and uPA. The network learns the structural relationship between these factors and the follow-up data. Examples of neural models for relapse-free survival are presented, which are based on data from 784 breast cancer patients who received their primary therapy at the Department of Obstetrics and Gynecology, Technische Universität München, Germany. The performance of the neural analysis as quantified by various indicators (likelihood, Kaplan-Meier curves, log-rank tests) was very high. For example, dividing the patients into two equally sized groups based on the neural score (i.e., cutoff = median score) leads to an estimated difference in relapse-free survival of 40% or better (80% vs. 40%) after 10 years in Kaplan-Meier analysis. Evidence for factor interactions as well as for time-varying impacts is presented. The neural network weights included in the models are significant at the 5% level. The use of neural network analysis and scoring in combination with strong tumor biological factors such as uPA and PAI-1 appears to result in a very effective risk group discrimination. Considerable additional comparison of data from different patient series will be required to establish the generalization capability more firmly. Nonetheless, the improvement of risk group discrimination represents an important step toward the use of neural networks for decision support in a clinical framework and in making the most of biological markers.

scholarly journals Effect of Pretreatment Renal Function on Treatment and Clinical Outcomes in the Adjuvant Treatment of Older Women With Breast Cancer: Alliance A171201, an Ancillary Study of CALGB/CTSU 49907

2016 ◽  
Vol 34 (7) ◽  
pp. 699-705 ◽  
Author(s):  
Stuart M. Lichtman ◽  
Constance T. Cirrincione ◽  
Arti Hurria ◽  
Aminah Jatoi ◽  
Maria Theodoulou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Early Stage ◽  
Single Agent ◽  
Hematologic Toxicity ◽  
End Points ◽  
Increased Risk ◽  
The Relationship

Purpose CALGB 49907 showed the superiority of standard therapy, which included either cyclophosphamide/doxorubicin (AC) or cyclophosphamide/methotrexate/fluorouracil over single-agent capecitabine in the treatment of patients age ≥ 65 with early-stage breast cancer. The treatment allowed dosing adjustments of methotrexate and capecitabine for pretreatment renal function. The purpose of the current analysis was to assess the relationship between pretreatment renal function and five end points: toxicity, dose modification, therapy completion, relapse-free survival, and overall survival. Methods Pretreatment renal function was defined as creatinine clearance (CrCl) using the Cockcroft-Gault equation. Multivariable logistic and proportional hazards regression were used to model separately for each regimen the relationship between CrCl and the first three binary end points and the last two time-to-event end points, respectively, after adjusting for variables of prognostic importance. Results Six hundred nineteen assessable patients were analyzed. The incidence of stage III (moderate) or stage IV (severe) renal dysfunction was 72%, 64%, and 75% for treatment with cyclophosphamide/methotrexate/fluorouracil, AC, and capecitabine, respectively. There was no relationship for any regimen between pretreatment renal function and the five end points. For AC, as CrCl increased, the odds of nonhematologic toxicity decreased (P = .008), whereas for capecitabine, as CrCl increased, the odds of experiencing toxicity of any type also increased (P = .035). Patients with renal insufficiency who received dose modifications were not at increased risk for complications compared with those who did not have renal insufficiency and received a full dose. Conclusion Excluding from clinical trials patients with renal insufficiency but good performance status on the basis of concern of excessive hematologic toxicity or poor outcomes may not be justified with appropriate dosing modifications. Results should be considered in the design of clinical trials for older patients.

scholarly journals High mutation burden of circulating cell‐free DNA in early‐stage breast cancer patients is associated with a poor relapse‐free survival

2020 ◽  
Vol 9 (16) ◽  
pp. 5922-5931
Author(s):  
Jouni Kujala ◽  
Jaana M. Hartikainen ◽  
Maria Tengström ◽  
Reijo Sironen ◽  
Veli‐Matti Kosma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Cell Free Dna ◽  
Free Survival ◽  
Free Dna ◽  
Mutation Burden

scholarly journals Prognostic Value of HER2-Low Expression in Non-Metastatic Triple-Negative Breast Cancer and Correlation with Other Biomarkers

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6059
Author(s):  
William Jacot ◽  
Aurélie Maran-Gonzalez ◽  
Océane Massol ◽  
Charlotte Sorbs ◽  
Caroline Mollevi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Histological Grade ◽  
Univariate Analysis ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Few Data

HER2-low breast cancer (i.e., HER 1+ or 2+, without gene amplification) is an emerging subtype for which very few data are available, especially within the triple-negative breast cancer (TNBC) group. Our aim was to evaluate HER2 expression and its prognostic value in a large retrospective series of patients with non-metastatic TNBC (median age: 57.7 years; range: 28.5–98.6). Among the 296 TNBC samples, 83.8% were HER2 0, 13.5% were HER2 1+, and 2.7% were HER2 2+ (HercepTestTM and 2018 ASCO/CAP guidelines for HER2 scoring). CK5/6 and/or EGFR-expressing androgen receptors and FOXA1-expressing tumors were classified as basal-like (63.8%) and molecular apocrine-like (MA, 40.2%), respectively. Compared with HER2 0 tumors, HER2 1+/2+ tumors exhibited a lower histological grade (1/2) (35.4% vs. 18.2%, p = 0.007) and MA profile (57.5% vs. 36.7%, p = 0.008). Moreover, patients with HER2 1+/2+ tumors were older (p = 0.047). After a median follow-up of 9.7 years, HER2 2+ tumors (compared with HER2 0/1+ tumors) were associated with worse relapse-free survival (RFS) (HR = 3.16, 95% CI [1.27; 7.85], p = 0.034) in a univariate analysis. Overall survival (OS) and RFS were not different in the HER2 0 and 1+/2+ groups. HER2 levels were not significantly associated with OS or RFS in a multivariate analysis.

Impact of Concurrent Versus Sequential Tamoxifen With Radiation Therapy in Early-Stage Breast Cancer Patients Undergoing Breast Conservation Treatment

2005 ◽  
Vol 23 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Eleanor E.R. Harris ◽  
Vasthi J. Christensen ◽  
Wei-Ting Hwang ◽  
Kevin Fox ◽  
Lawrence J. Solin
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Breast Conservation ◽  
Tamoxifen Therapy ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Conservation Treatment ◽  
Breast Conservation Treatment

Purpose To assess the impact of sequencing of tamoxifen and radiation therapy (RT) on outcomes in early-stage breast cancer. Patients and Methods This retrospective study evaluates the effect of the sequence of tamoxifen with RT on outcomes in stage I to II breast cancer patients who underwent breast-conservation treatment (BCT) and received adjuvant tamoxifen, with or without adjuvant chemotherapy. Patients were grouped as concurrent (tamoxifen given during RT followed by continued tamoxifen; 174 patients) and sequential (RT followed by tamoxifen; 104 patients). Results Median follow-up after RT was 8.6 years for both groups. The pathologic T and N stage, race, estrogen and progesterone status, number of positive nodes, and RT were comparable between the two groups (all P ≥ .08). More women age 49 years or younger and women who received chemotherapy were in the sequential group than the concurrent group (6% and 25%, respectively; P < .0001). The sequence of tamoxifen therapy did not influence 10-year local recurrence rates (sequential, 7%; concurrent, 3%; P = .52), overall survival (sequential, 86%; concurrent, 81%; P = .64), or relapse-free survival (sequential, 76%; concurrent, 85%; P = .35). When adjusting age and chemotherapy use in the multivariable Cox model, hazard ratios comparing sequential versus concurrent tamoxifen therapy were 1.56 (95% CI, 0.87 to 2.79), 1.23 (95% CI, 0.63 to 2.41), and 1.22 (95% CI, 0.33 to 4.49) for the overall survival, relapse-free survival, and local recurrence, respectively. Conclusion The therapeutic regimens of tamoxifen given concurrently or sequentially with RT both appear to be reasonable options for patients treated with BCT.

Capecitabine in operable triple receptor–negative breast cancer: A subgroup analysis of a randomized phase III trial.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 292-292
Author(s):  
C. M. Kelly ◽  
M. C. Green ◽  
K. Broglio ◽  
L. Pusztai ◽  
E. Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Subgroup Analysis ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Phase Iii ◽  
Relapse Free Survival ◽  
Phase Iii Trial ◽  
Free Survival

292 Background: Recent data suggest that patients with operable triple negative breast cancer (TNBC) may derive greater benefit from the addition of capecitabine to anthracycline-taxane regimens. Methods: We examined pathological complete response (pCR), relapse-free survival (RFS) and overall survival (OS) in patients with TNBC randomized to paclitaxel 80mg/m2 weekly (WP) x 12 followed by fluorouracil (500mg/m2), epirubicin (100mg/m2), cyclophosphamide (500mg/m2) every 3 weeks x 4 cycles (FEC) vs. docetaxel (75mg/m2) 3 weekly and capecitabine D1-14 (1500mg/m2 daily; DX) followed by FEC. Patients were stratified by timing of chemotherapy (preoperative vs. adjuvant). Results: 149 patients with TNBC comprising 25% of all patients randomized (N=601). Median age; 49 years (IQR; 41 to 55). The number and proportion of patients by stage were; I (n=32: 21.5%), IIA (n=72: 48.3%), IIB (n=34: 22.8%), IIIA (n=9: 6.0%) and IIIC (n=2; 1.3%). Preoperative therapy was administered to 58 patients (39%) and adjuvant to 91 (61%). There were 17 events (21%) in the DX arm and 10 events (15%) in the WP arm (P=0.36) including 11 distant recurrences in the DX arm and 9 in the WP arm (P=0.99). We observed a pCR in 11 patients (37%) and 10 (36%) in the DX and WP arms respectively (P=0.94). The odds ratio for pCR for patients with TNBC given DX vs. WP was 0.98 (95% CI; 0.33 to 2.80: P=0.94). At 50-months median follow-up the RFS and OS in patients with TNBC randomized to DX or WP was 77% (66 to 86%) and 83% (73 to 92%) (P=0.41) and 78% (67 to 87%) and 87% (77 to 95%) (P=0.16) respectively. RFS and OS for WP vs. DX for non-TNBC was 93% (87 to 95%) and 92% (88 to 96%) (p=0.91) and 96% (92 to 98%) and 97% (94 to 99%) for WP and DX respectively (P=0.39). Conclusions: In this unplanned subgroup analysis there was no difference in pCR, RFS or OS in patients with operable TNBC randomized to WP or DX however, power is limited and should be considered when interpreting these data.

Adjuvant treatment of early-stage HER2+ elderly breast cancer patients: A retrospective, multicenter French study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 636-636
Author(s):  
Philippe Barthelemy ◽  
Karine Bassot ◽  
Florence Joly ◽  
Isabelle Ray Coquard ◽  
Gilles Freyer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Adjuvant Treatment ◽  
Early Stage ◽  
Single Agent ◽  
Her2 Status ◽  
Routine Practice ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer

636 Background: Trastuzumab (T) is the standard of care for the adjuvant treatment of early stage, HER2+ breast cancer (BC). However, few data are available for elderly HER2+ breast cancer patients in this setting. In this current study, the patterns of care for elderly HER2+ early stage BC in 7 French cancer centres was evaluated. Methods: Medical records of all consecutive early stage HER2+ BC patients over 70 years old treated between 2006 and 2011 among participating centres were retrospectively reviewed. Specific factors such as age, comorbidities, tumor stage, grade, ER/PR and HER2 status, treatment characteristics, follow-up and cardiotoxicity data were analysed. Results: One hundred and two patients were identified, median age 75.4 (range 70-95). Elderly patients presented mostly (57%) large tumors (pT ≥2), and positive lymph node involvement (n=61). Trastuzumab-based adjuvant treatment was administered in 62% of patients (n=63). 54% of patients (n=55) received adjuvant chemotherapy whereas five patients received neoadjuvant chemotherapy. Chemotherapy without T was administered in 2 additional patients. Anthracyclines (A)-Taxanes (Ta) combination-based chemotherapy was given in 27% of patients (n=16), whereas 38% received a Ta-based chemotherapy (n=23), 35% (n=19) an A-based chemotherapy. Five patients received single-agent T. Treatment delays for T were required in 37% of patients (n=23) among whom 15 and 8 permanently or temporarily stopped T, respectively. The most frequent reason for interrupting or delaying therapy was cardiotoxicity (n=12) as well as patients refusal (n=7). A ≥ 10% decrease in LVEF was observed in 18/63 (29%) of patients, among whom T was stopped in 12. After a median 33 months follow-up, the median progression-free survival was not reached in patients receiving T-based therapy. The 2 and 3-year PFS rate were 94 and 89.5%, respectively. Conclusions: In routine practice only 62% of elderly early stage HER2+ BC patients are treated with a neoadjuvant or adjuvant T-based regimen. However, less than 50% of all patients completed their therapy. A-based chemotherapy was administered in around 60% of treated patients, and could explain cardiotoxicity in this setting.

Serum CA 15.3, CEA and ESR Patterns in Breast Cancer

1997 ◽  
Vol 12 (4) ◽  
pp. 168-173 ◽  
Author(s):  
M. Rubach ◽  
J.J. Szymendera ◽  
J. Kamińska ◽  
M. Kowalska
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Peak Level ◽  
Serum Markers ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Ca 15.3

Serum CA 15.3, CEA and ESR were longitudinally determined in 298 patients with breast cancer during postsurgical follow-up and/or therapy. Observation lasted until the death of the patient or at least for three years. With regard to longitudinal serum markers and ESR curves, four different patterns have been identified: pattern I: the markers and ESR stayed at normal levels; pattern II: the markers and ESR decreased from a peak level; pattern III: the markers and ESR fluctuated widely; pattern IV: the markers and ESR increased steadily. We have looked at overall survival (OS) and relapse-free survival (RFS) versus longitudinal CA 15.3, CEA and ESR patterns. Univariate Cox regression analysis showed that OS and RFS were significantly associated with all four patterns.

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