scholarly journals Obesity and Risk of Recurrence or Death After Adjuvant Endocrine Therapy With Letrozole or Tamoxifen in the Breast International Group 1-98 Trial

2012 ◽  
Vol 30 (32) ◽  
pp. 3967-3975 ◽  
Author(s):  
Marianne Ewertz ◽  
Kathryn P. Gray ◽  
Meredith M. Regan ◽  
Bent Ejlertsen ◽  
Karen N. Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Normal Weight ◽  
Baseline Body Mass Index ◽  
Risk Of Recurrence ◽  
Breast International Group ◽  
International Group ◽  
Free Interval

Purpose To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up. Patients and Methods This report analyzes 4,760 patients with breast cancer randomly assigned to 5 years of monotherapy with letrozole or tamoxifen in the BIG 1-98 trial with available information on BMI at randomization. Multivariable Cox modeling assessed the association of BMI with disease-free survival, overall survival (OS), breast cancer–free interval, and distant recurrence-free interval and tested for treatment-by-BMI interaction. Median follow-up was 8.7 years. Results Seventeen percent of patients have died. Obese patients (BMI ≥ 30 kg/m2) had slightly poorer OS (hazard ratio [HR] = 1.19; 95% CI, 0.99 to 1.44) than patients with normal BMI (< 25 kg/m2), whereas no trend in OS was observed in overweight (BMI 25 to < 30 kg/m2) versus normal-weight patients (HR = 1.02; 95% CI, 0.86 to 1.20). Treatment-by-BMI interactions were not statistically significant. The HRs for OS comparing obese versus normal BMI were HR = 1.22 (95% CI, 0.93 to 1.60) and HR = 1.18 (95% CI, 0.91 to 1.52) in the letrozole and tamoxifen groups, respectively. Conclusion There was no evidence that the benefit of letrozole over tamoxifen differed according to patients' BMI.

scholarly journals Assessing the Clinical Benefit of Systemic Adjuvant Therapies for Early Breast Cancer

2017 ◽  
Vol 77 (10) ◽  
pp. 1079-1087 ◽  
Author(s):  
Volker Möbus ◽  
Susanne Hell ◽  
Marcus Schmidt
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Clinical Benefit ◽  
Early Stage ◽  
Survival Rates ◽  
Disease Free Survival ◽  
New Drugs ◽  
Early Stage Breast Cancer ◽  
Risk Of Recurrence ◽  
Adjuvant Therapies

AbstractOncologic therapy is currently undergoing significant changes. A number of innovative targeted medications currently in clinical development have raised high expectations. With that in mind, discussions about terms such as “clinical benefit” and “clinical relevance” are highly topical. This also applies to further developments in the field of adjuvant systemic therapies for early-stage breast cancer. As the treatment aim is curative, assessment of the clinical benefit of adjuvant therapies must be largely based on efficacy outcomes. The focus must be on improving disease-free survival rates and lowering the risk of recurrence. Because of the current low mortality rates, statements about overall survival rates are only possible after very long observation periods. Consequently, new drugs in adjuvant therapies should be considered as offering a clinical benefit, if they reduce the risk of recurrence below current low levels of risk. The evidence for established adjuvant therapy standards in early-stage breast cancer can be used as objective criteria for comparison. This review article considers the requirements for clinical benefit of new adjuvant therapies for early breast cancer, based on examples from adjuvant endocrine therapy, adjuvant polychemotherapy and adjuvant anti-HER2 therapy.

Cholesterol, Cholesterol-Lowering Medication Use, and Breast Cancer Outcome in the BIG 1-98 Study

2017 ◽  
Vol 35 (11) ◽  
pp. 1179-1188 ◽  
Author(s):  
Signe Borgquist ◽  
Anita Giobbie-Hurder ◽  
Thomas P. Ahern ◽  
Judy E. Garber ◽  
Marco Colleoni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
Distant Recurrence ◽  
Cholesterol Lowering ◽  
Hormone Receptor Positive ◽  
Cholesterol Levels ◽  
Free Interval

Purpose Cholesterol-lowering medication (CLM) has been reported to have a role in preventing breast cancer recurrence. CLM may attenuate signaling through the estrogen receptor by reducing levels of the estrogenic cholesterol metabolite 27-hydroxycholesterol. The impact of endocrine treatment on cholesterol levels and hypercholesterolemia per se may counteract the intended effect of aromatase inhibitors. Patients and Methods The Breast International Group (BIG) conducted a randomized, phase III, double-blind trial, BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. Systemic levels of total cholesterol and use of CLM were measured at study entry and every 6 months up to 5.5 years. Cumulative incidence functions were used to describe the initiation of CLM in the presence of competing risks. Marginal structural Cox proportional hazards modeling investigated the relationships between initiation of CLM during endocrine therapy and outcome. Three time-to-event end points were considered: disease-free-survival, breast cancer–free interval, and distant recurrence–free interval. Results Cholesterol levels were reduced during tamoxifen therapy. Of 789 patients who initiated CLM during endocrine therapy, the majority came from the letrozole monotherapy arm (n = 318), followed by sequential tamoxifen-letrozole (n = 189), letrozole-tamoxifen (n = 176), and tamoxifen monotherapy (n = 106). Initiation of CLM during endocrine therapy was related to improved disease-free-survival (hazard ratio [HR], 0.79; 95% CI, 0.66 to 0.95; P = .01), breast cancer–free interval (HR, 0.76; 95% CI, 0.60 to 0.97; P = .02), and distant recurrence–free interval (HR, 0.74; 95% CI, 0.56 to 0.97; P = .03). Conclusion Cholesterol-lowering medication during adjuvant endocrine therapy may have a role in preventing breast cancer recurrence in hormone receptor–positive early-stage breast cancer. We recommend that these observational results be addressed in prospective randomized trials.

Pharmacogenetic profiling for oxaliplatin-based adjuvant chemotherapy (CT) benefit in stage II-III colon cancer (CC) patients: A GEMCAD study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3618-3618
Author(s):  
Jaime Feliu ◽  
Ana Custodio ◽  
Juan Moreno ◽  
Jorge Aparicio ◽  
Javier Gallego ◽  
...  
Keyword(s):  
Early Stage ◽  
Disease Free Survival ◽  
Treatment Resistance ◽  
Stage Ii ◽  
Nucleotide Polymorphisms ◽  
Genotype Relative Risk ◽  
Prognostic Information ◽  
Combined Analysis ◽  
Risk Of Recurrence

3618 Background: Identifying molecular biomarkers for tumour recurrence is critical in successfully selecting early-stage CC patients who are more likely to benefit from adjuvant CT. We tested whether single nucleotide polymorphisms (SNP) within genes involved in biological pathways of interest for CC progression and treatment resistance would predict the risk of recurrence in stage II-III CC patients treated with oxaliplatin and fluoropyrimidines-based adjuvant CT. Methods: Genomic DNA was extracted from formalin-fixed paraffin-embedded samples from 202 surgically treated high-risk stage II (29.7%) and stage III (70.29%) CC patients receiving adjuvant CT (25.24% FOLFOX, 74.75% XELOX) from January 2004 to December 2008. Minimum follow-up was 36 months. Genotyping was performed for 62 SNPs in 31 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 stage II-III CC. Results: After a median follow-up of 51.4 months (7-96), 63 patients (31.18%) had experienced a relapse and 31 (15.34%) had died. Three-year disease-free survival (DFS) and overall survival (OS) were 72.2% (+/-0.032) and 89.1% (+/-0.022), respectively. Multivariate analysis showed that the risk of recurrence for patients with the E-selectine rs3917412 G>A G/G genotype was higher than for those with any A allele genotype [relative risk (RR): 2.02, 95% confidence interval (CI): 1.09-3.73, p=0.024]. In haplotype analysis, patients harboring the E-selectine rs3917412 G>A G/G and methylentetrahydrofolate reductase (MTHFR) rs1801133 C>T T/T haplotype had a higher risk of developing tumor recurrence compared to the E-selectine rs3917412 G>A any A and/or MTHFR rs1801133 C>T any C haplotype (RR: 3.39, 95% CI, 1.51-7.62, p=0.003). The ability to predict recurrence of this combined analysis was independently validated in the second cohort (RR: 3.75, 95% CI, 1.32-10.68, p=0.013). Conclusions: E-selectine and MTHFR SNPs were found to be independent prognostic markers for stage II-III CC patients, suggesting that this combined analysis provides additional prognostic information to that offered by clinicopathologic variables.

Inflammatory markers in early-stage breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11537-e11537
Author(s):  
Hilbrahim Petekkaya ◽  
Sercan Aksoy ◽  
Gizem Gecmez ◽  
Emre Kulahcioglu ◽  
Alexis K. Okoh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Markers ◽  
Early Stage ◽  
Disease Free Survival ◽  
Serum Markers ◽  
Early Stage Breast Cancer ◽  
Chemotherapy Response ◽  
Significant Difference ◽  
Stage Ia

e11537 Background: In a few number of studies a possible relationship between inflammatory markers and the prognosis, chemotherapy response and survival in breast cancer has been reported. The aim of this study is to point out the place of serum markers as a prognostic factor in early stage breast cancer. Methods: This study was conducted in Hacettepe University Cancer Institute. Patients operated and stage IA to III C for breast cancer between December 2009 and June 2012 were included the study. Before the any adjuvant therapy inflammation markers were studied. Results: A total of 704 patients were included in the study. The median age of the patients was 50 (25-92). 42,8% of the patients were premenopausal and 48,2% postmenopausal. The median follow up period for the whole study group was 22 months (3-287). We studied the CRP, erythrocyte sedimentation rate, B2 microglobulin, LDH, albumin, and ferritin studied and values for each marker were grouped as high and normal. There was no statistically significant difference in disease free survival and overall survival for each marker who had high and normal levels. Conclusions: We did not found any inflammatory markers as a prognostic value. However our follow up time is short and we should be wait for more mature data.

scholarly journals Prognostic and Predictive Value of Centrally Reviewed Ki-67 Labeling Index in Postmenopausal Women With Endocrine-Responsive Breast Cancer: Results From Breast International Group Trial 1-98 Comparing Adjuvant Tamoxifen With Letrozole

2008 ◽  
Vol 26 (34) ◽  
pp. 5569-5575 ◽  
Author(s):  
Giuseppe Viale ◽  
Anita Giobbie-Hurder ◽  
Meredith M. Regan ◽  
Alan S. Coates ◽  
Mauro G. Mastropasqua ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Postmenopausal Women ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Labeling Index ◽  
Ki 67 ◽  
Treatment Benefit ◽  
Breast International Group ◽  
International Group

Purpose To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. Patients and Methods Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. Results Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). Conclusion Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.

Accelerated Treatment of Breast Cancer

2001 ◽  
Vol 19 (7) ◽  
pp. 1993-2001 ◽  
Author(s):  
Frank A. Vicini ◽  
Kathy L. Baglan ◽  
Larry L. Kestin ◽  
Chris Mitchell ◽  
Peter Y. Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Time ◽  
Reference Group ◽  
Early Stage ◽  
Estrogen Receptor Status ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Patients ◽  
Tumor Bed

PURPOSE: Radiation therapy (RT) restricted to the tumor bed, by means of an interstitial implant, and lasting 4 to 5 days after lumpectomy was prospectively evaluated in early-stage breast cancer patients treated with breast-conserving therapy (BCT). The goals of the study were to determine whether treatment time can be reduced and whether elective treatment of the entire breast is necessary. MATERIALS AND METHODS: Between January 1993 and January 2000, 174 cases of early-stage breast cancer were managed with lumpectomy followed by RT restricted to the tumor bed using an interstitial implant. Each brachytherapy patient was matched with one external-beam RT (ERT) patient derived from a reference group of 1,388 patients treated with standard BCT. Patients were matched for age, tumor size, histology, margins of excision, absence of an extensive intraductal component, nodal status, estrogen receptor status, and tamoxifen use. Median follow-up for both the ERT and brachytherapy groups was 36 months. RESULTS: No statistically significant differences were noted in the 5-year actuarial rates of ipsilateral breast treatment failure or locoregional failure between ERT and brachytherapy patients (1% v 0%, P = .31 and 2% v 1%, P = .63, respectively). In addition, there were no statistically significant differences noted in rates of distant metastasis (6% v 3%, P = .24), disease-free survival (87% v 91%, P = .55), overall survival (90% v 93%, P = .66), or cause-specific survival (97% v 99%, P = .28). CONCLUSION: Accelerated treatment of breast cancer using an interstitial implant to deliver radiation to the tumor bed alone over 4 to 5 days seems to produce 5-year results equivalent to those achieved with conventional ERT. Extended follow-up will be required to determine the long-term efficacy of this treatment approach.

The Head to Head trial: Letrozole vs anastrozole as adjuvant treatment of postmenopausal patients with node positive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10672-10672 ◽  
Author(s):  
R. De Boer ◽  
H. A. Burris ◽  
A. Monnier ◽  
H. Mouridsen ◽  
J. A. O’Shaughnessy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Safety Data ◽  
Disease Free Survival ◽  
Her2 Status ◽  
Open Label ◽  
Specific Patient ◽  
Risk Of Recurrence ◽  
Cancer Data

10672 Introduction: Aromatase Inhibitors (AIs) have demonstrated both efficacy and safety advantages over tamoxifen (T) in all treatment settings in breast cancer (BC) and are becoming the new standard of care as endocrine therapy for postmenopausal patients (PM) with BC. Rationale: Cumulative evidence suggests that all AIs may not be the same, raising the question of whether there is a superior AI, and whether any specific patient populations derive differing degrees of benefit from a particular AI. In the ATAC trial, evaluating anastrozole (A) in PM patients with early breast cancer (EBC), at 33 months median follow up the risk of recurrence in the hormone receptor positive (HR+) population was reduced by 22%.The BIG 1–98 Trial, evaluating letrozole (L) in PM women with EBC, showed a significant benefit in favor of L over T at a median follow up of 26 months, with a 19% reduction in the risk of recurrence; in subgroup analyses, L significantly decreased the risk of recurrence in LN+ patients and in patients who received adjuvant chemotherapy. This study is a head to head comparison of L and A in HR+, LN+ PM patients with EBC and aims to compare L vs A in the adjuvant treatment of these patients. Design and Methods: This is a Phase IIIb open-label, randomized, multicentre study including 4000 PM patients from up to 250 international sites. PM patients with HR+, LN+ BC who have recently undergone surgery for primary BC will be randomized to either receive L 2.5 mg or A 1 mg daily. Treatment will commence following completion of standard chemotherapy (if given) and concurrently with radiotherapy (if given)Patients will receive treatment until disease recurrence/relapse for up to 5 years. Patients will be stratified by number of LN and HER2 status. The primary objective is disease free survival at 5 years for L and A. Secondary objectives include safety, overall survival, time to distant metastases and time to contralateral breast cancer. Data analysis will be conducted by an independent group of investigators. Summary: Updated patient accrual figures, including any available early safety data, will be presented at the meeting. No significant financial relationships to disclose.

Modeling longer-term efficacy of neratinib in the extended adjuvant setting for early-stage breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12011-e12011
Author(s):  
Mark D. Danese ◽  
Marc Halperin ◽  
Deepa Lalla ◽  
Bin Yao ◽  
John Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Link Function ◽  
Adjuvant Setting ◽  
Term Efficacy ◽  
Interaction Terms ◽  
Parametric Survival

e12011 Background: Long-term efficacy in the extended adjuvant setting requires a long follow-up. In the ExteNET trial, neratinib was given for a year and invasive disease-free survival (iDFS) assessed at 2 and 5 years. In women with HER2+ hormone receptor positive (HR+) cancer who initiated neratinib, the observed difference in iDFS between neratinib and placebo at 5 years (4.5%) was greater than at 2 years (3.7%). The objective of these analyses was to extrapolate the effect of neratinib on iDFS beyond 5 years in patients with HER2+/HR+ early stage breast cancer who initiated treatment after receiving adjuvant trastuzumab. Methods: We analyzed the 5-year follow-up of the ExteNET trial using flexible spline-based parametric survival models to project iDFS risk at 10 years. Analyses included only HR+ patients. Several model specifications were explored including various combinations of the following variables: treatment as a time varying covariate, nodal status (0, 1-3, ≥4 nodes), and months from last trastuzumab treatment to randomization. The regression models included different combinations of interaction terms, either a proportional hazards or a proportional odds (PO) link function, and either 2 or 6 knots. The model fit was compared using Akaike Information Criterion (AIC). Results: In general, the fit statistics among the 16 models were comparable; however, the model with the lowest AIC included no interaction terms, 2 knots, and the PO link function. The mean iDFS event rate at 10 years was estimated to be 12.2% for neratinib and 18.9% for placebo for a difference of 6.8% (range across 16 models: 6.8%-7.8%). The recurrence rate and the difference between treatment groups were largest in women with ≥4 positive nodes. Conclusions: Based on these analyses, the projected 10-year difference in iDFS between placebo and neratinib patients seems likely to persist. However, because the data was limited to 5 years, we could not include the effect of hormonal therapy cessation. Also, low event rates in the node negative group may require longer follow-up to evaluate. In absence of longer-term data for neratinib, flexible parametric survival modeling of the iDFS suggests that the effect of neratinib therapy may remain stable.

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