bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract S2-3: The Impact of Body Mass Index (BMI) on the Efficacy of Adjuvant Endocrine Therapy in Postmenopausal Hormone Sensitive Breast Cancer (BC) Patients; Exploratory Analysis from the TEAM Study
Authors: Seynaeve C , Hille E , Hasenburg A , Rea D , Markopoulos C , Hozumi Y , Putter H , Nortier H , van Nes J , Dirix L , van de Velde C. 
Published: April 2011

Abstract
Background: Obesity is associated with an increased risk of breast cancer (BC) recurrence and decreased survival, also in case of adjuvant endocrine therapy. It is still not clear whether the activity of aromatase inhibitors and tamoxifen (T) given as adjuvant therapy is affected by body mass index (BMI), although both drugs are widely prescribed. In this analysis, we explored the outcome of TEAM patients (pts) treated with exemestane (E) versus T (2.75 yrs), and with E versus T followed by E (T/E) (5 yrs) in relation to BMI.
Patients and Methods: The TEAM trial is a randomized, international phase III study in postmenopausal hormone sensitive early BC pts comparing the activity and safety of adjuvant E (25 mg daily) or the sequence of T (20 mg daily) followed by E (T/E), both regimens given for five years. WHO BMI definitions were used: normal 18.5-24.9 kg/m2, overweight 25-30 kg/m2, obese &gt;30 kg/m2. Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method; results were compared by using the log-rank test and Cox proportional hazard modelling adjusted for country.
Results: Weight and height was known in 4741 pts. Mean BMI was 26.9 kg/m2 (SD 4.9); 39% had a normal BMI, 36.9% overweight, and 23.3% of pts was obese. Underweight pts (n=41, 0.9%) were excluded from further analysis. At 2.75 yrs (E vs T) disease relapse in normal weight, overweight and obese pts using E was observed in 8.1%, 6.8% and 7.5% respectively (p=0.57), and in 9.1%, 8.8%, and 12.5%, respectively (p=0.06) of pts using T. The hazard ratio (HR for risk of relapse on E vs T) in the three subgroups was 0.91 (95%CI 0.66-1.24), 0.78 (95%CI 0.55-1.089), and 0.57 (95%CI 0.39-0.84, p=0.004), respectively. At a median follow-up of 5.1 years, disease relapse in normal weight, overweight and obese pts using E occurred in 14.8%, 15.1% and 15.1%, respectively; and in pts using T in 17.0%, 16.9%, and 18.3%, respectively. Regarding DFS, the HR in normal weight, overweight, and obese pts was 0.87 (95%CI 0.69-1.10), 0.88 (95%CI 0.70-1.11), and 0.75 (95%CI 0.56-1.01, p=0.058), respectively, and with respect to OS 0.87 (95%CI 0.65-1.15, p= 0.32), 0.89 (95%CI 0.67-1.18, p= 0.43), and 0.71 (95% CI 0.51-1.01, p= 0.053), respectively.
Conclusions: After 2.75 years more disease events were observed in obese women using tamoxifen, which was not seen in obese exemestane users, whereas at 5 years these differences in disease recurrences disappeared in this group. In contrast to recent reports, there seems to be a difference regarding the influence of a high BMI on recurrence rate between tamoxifen and the aromatase inhibitor exemestane. Further research on this topic is warranted.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-3.
Abstract S2-7: Toxicity of Adjuvant Endocrine Therapy in Postmenopausal Breast Cancer Patients
Authors: Amir E , Ocaña A , Niraula S , Carlsson L , Seruga B. 
Published: April 2011

Abstract
Purpose: To determine differences in serious adverse events (AEs) associated with aromatase inhibitors (AIs) compared with tamoxifen, and to explore whether these AEs might be ameliorated by switching to AIs after 2-3 years of tamoxifen.
Materials and Methods: Published data from trials contributing to the Aromatase Inhibitor Overview Group were included in a meta-analysis. Odds ratios (OR), 95% confidence intervals (CI) and absolute risks (number needed to treat [NNT] associated with one AE) were computed for serious AEs
Results: Any duration of AIs was associated with a higher probability of developing cardiovascular disease (OR 1.20, p=0.01; NNT 143) and bone fractures (OR 1.48, P&lt;0.00001; NNT 34), but a reduced probability of venous thrombosis (OR 0.53, P&lt;0.00001; NNT 67) and endometrial carcinoma (OR 0.32, P&lt;0.00001; NNT 200). The risks of individual serious AEs were similar for upfront AIs and for switching to AIs after tamoxifen. However, compared with 5 years of tamoxifen, there was a non-significant trend towards increased death without recurrence with upfront AIs (OR 1.12, p=0.16), but lower with switching to AIs after tamoxifen (OR 0.74, p=0.03).
Conclusion: Treatment with AIs is associated with a statistically significant increase in cardiovascular risk, which is of similar magnitude to the risk of venous thrombosis and endometrial cancer with 5-years of tamoxifen. While switching to AIs does not appear to reduce the risk for the development of serious AEs when compared to upfront use of AIs, fewer deaths unrelated to breast cancer occur with switching than with upfront strategies.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-7.
Abstract S3-1: Lapatinib vs Trastuzumab in Combination with Neoadjuvant Anthracycline-Taxane-Based Chemotherapy: Primary Efficacy Endpoint Analysis of the GEPARQUINTO STUDY (GBG 44)
Authors: Untch M , Loibl S , Bischoff J , Eidtmann H , Kaufmann M , Blohmer J-U , Hilfrich J , Strumberg D , Fasching PA , Kreienberg R , Tesch H , Hanusch C , Gerber B , Rezai M , Jackisch C , Huober J , Kuehn T , Nekljudova V , von Minckwitz G. 
Published: April 2011

Abstract
Background: The tyrosine-kinase inhibitor lapatinib (L) has shown to improve efficacy of cytotoxic and endocrine treatment in HER2-positive metastatic breast cancer (BC). Improved pathological complete response (pCR) rates were demonstrated by adding trastuzumab (T) to neoadjuvant chemotherapy. However, so far no head-to-head comparison of the two anti-HER2-agents is available. One primary aim of the GeparQuinto study was to improve the pCR rate by adding L instead of T to anthracycline-taxane-based neoadjuvant chemotherapy. We previously reported interim safety data of this study showing more diarrhea, skin changes, and hot flushes, but no cardiac events with L compared to T (von Minckwitz G et al, Ann Oncol 2010 in press).
Patients and Methods: Patients (P) with untreated HER2-positive BC were eligible if they had cT3/4a-d; or estrogen (ER) and progesterone (PgR) receptor-negative; or ER/PgR-positive tumors with clinically N+ (for cT2) or pNSLN+ (for cT1) disease, and no increased cardiac risks. P were randomized to receive 4 cycles epirubicin/cyclophosphamide (EC) (90/600 mg/m2) q3w followed by 4 cycles docetaxel (D) (100mg/m2) given in combination with either T 6 (loading dose 8) mg/kg every 3 weeks or L 1000-1250 mg/d throughout all cycles. pCR was defined as no invasive or non-invasive tumor residuals in breast and nodes. We assumed a pCR rate of 26% with ECT-DT (based on GeparQuattro) and expected a pCR of 37% for ECL-DL (odds ratio 1.67). A two-sided Pearson's Chi2 with α=0.05 and β=0.20 calculated a sample size of 613 P.
Results: Between May ‘07 and June ‘10 597 P were randomized to ECT-DT (N=299) and ECL-DL (N=298). Median tumor size was 40/40 [T/L] mm (clinically) and 28/29 mm (sonographically); 4.7%/4.3% had T4a-c, 14.8%/14.2% T4d, 2.9%/1.8% bilateral, 17.0%/17.7% multifocal, and 9.0%/12.1% multicentric disease, 96.7%/97.9% had non-lobular, 45.6%/48.9% grade 3, 70.0%/67.7% node-positive, and 56.5%/56.0% ER and PgR-negative disease. Baseline characteristics were well balanced between the treatment arms. The last randomized P will have surgery early Dec'10. Final results on histological response and surgical outcome will be reported.
Conclusion: The GeparQuinto trial will provide for the first time randomized phase III efficacy data on the comparison of L and H in combination to chemotherapy for patients with early breast cancer. As pCR has been confirmed as being a surrogate marker for long-term outcome after T treatment, this result will give insight on the overall efficacy of L in patients with early breast cancer.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S3-1.
Abstract S3-3: First Results of the NeoALTTO Trial (BIG 01-06/EGF 106903): A Phase III, Randomized, Open Label, Neoadjuvant Study of Lapatinib, Trastuzumab, and Their Combination Plus Paclitaxel in Women with HER2-Positive Primary Breast Cancer
Authors: Baselga J , Bradbury I , Eidtmann H , Di Cosimo S , Aura C , De Azambuja E , Gomez H , Dinh P , Fauria K , Van Dooren V , Paoletti P , Goldhirsch A , Chang T-W , Lang I , Untch M , Gelber RD , Piccart-Gebhart M 
Published: April 2011

Abstract
Background: The addition of trastuzumab to neoadjuvant chemotherapy has significantly improved pathological complete response (pCR) in patients with HER2-positive early breast cancer (BC). Lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor, combined with chemotherapy has significantly improved progression free survival in patients with metastatic HER2-positive BC. Additionally, lapatinib combined with trastuzumab improved disease-free and overall survival in patients with metastatic HER2-positive BC. The NeoALTTO trial is testing the efficacy of lapatinib, trastuzumab or their combination together with paclitaxel when given as neoadjuvant therapy in patients with HER2-positive BC. Material and Methods: NeoALTTO is an international, multicenter, randomized study comparing the efficacy of lapatinib plus paclitaxel, versus trastuzumab plus paclitaxel, versus concomitant lapatinib and trastuzumab plus paclitaxel given as neoadjuvant treatment in HER2- positive primary BC. From January, 2008, to December, 2009, 455 patients were randomized from 99 participating sites. Patients were randomized to receive either lapatinib 1500 mg/d (154 pts), or trastuzumab 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly (149 pts), or lapatinib 1000 mg/d with trastuzumab for a total of 6 weeks (152 pts). After this biological window, patients continued on the same targeted therapy plus weekly paclitaxel 80 mg/m2 for a further 12 weeks, until definitive surgery (total neoadjuvant therapy duration of 18 weeks). After surgery, patients received 3 cycles of adjuvant FEC followed by the same targeted therapy as in the biological window of the neoadjuvant phase for a further 34 weeks (to complete 52 weeks of anti-HER2 therapy). The primary objective of the study is to evaluate and compare among the three arms the rate of pCR, defined as the absence of invasive cancer in the breast at the time of surgery. Secondary objectives include objective response rate, safety, pathologic node-negative status, rate of conversion to breast conservation, disease-free survival and overall survival. All patients underwent tumor biopsies for comparative pharmacodynamic analyses before beginning therapy and on day 15 of the biological therapy window. A subset of patients also participated in PET/CT and circulating tumor cells substudies. Results: The last breast surgery was performed in May 2010. Data cleaning and analysis will be complete by November 2010 and results for safety and the primary objective (pCR) of this important phase III trial will be presented at the meeting.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S3-3.
Abstract S3-5: Discordance in Hormone Receptor and HER2 Status in Breast Cancer during Tumor Progression
Authors: Lindstrom LS , Karlsson E , Wilking U , Bergh J. 
Published: April 2011

Abstract
Background: In the metastatic situation therapy management is routinely based on primary tumor estrogen receptor (ER), progesterone receptor (PR) and HER2 status. Alterations in these therapy predictive factors may lead to altered management.
Methods: Breast cancer patients in the Stockholm health care region who relapsed from 1997 through 2007 were included and intra-individual primary tumor and relapse ER status, PR status and HER2 status accessed. Biochemical, immunohistochemical (IHC) or immunocytochemical (ICC) methods were used for determination of ER and PR (cut-off value of 0.05 fmol/µg DNA and 10%), respectively. For HER2, primary tumors were investigated using IHC with two or three monoclonal antibodies, confirmed by Fluorescence In Situ Hybridization (FISH) for IHC 2+ and 3+ and recurrences using ICC or FISH. The pathology laboratory at Karolinska University Hospital have continuously participated in quality assurance programs for hormonal receptor and HER2 analysis.
Results: In 477, 447, and 108 patients, ER, PR and HER2 information was assessed from both primary tumor and relapse. Intra-individual primary tumor and relapse information for ER, PR and HER2 was available in 68 patients. ER and PR status changed in 26% and 35% from positive in primary tumor to negative in relapse tumor, and 7% and 6% changed from negative to positive, respectively. In 11 (10%) patients, tumors changed HER2 status, seven patients (7%) changed from HER2 positive to HER2 negative and 4 patients (4%) from HER2 negative to HER2 positive. Univariate analyses showed a significantly (log rank P&lt;0.0005) differential survival in women related to intra-individual primary and relapse ER and PR status, respectively. In addition, a significant two-fold increased risk of dying in ER positive women changing to ER negative, compared to stable ER positive women, was noted using a multivariable proportional hazard model.
Conclusions: More than every third patient changed ER and PR status and one patient in ten changed HER2 status during tumor progression. Intra-individual primary and relapse ER and PR status was significantly associated with differential survival in women. In addition, patients loosing ER had an almost two-fold increased risk of dying compared to concordant ER positive patients. Thus, altered management through tumor progression may improve survival and implies the need for hormonal receptor and HER2 investigations in metastatic lesions.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S3-5.
Abstract S4-3: Ten-Year Follow-Up Analysis of the BICRG 001 Trial Confirms Superior DFS and OS Benefit of Adjuvant TAC (Docetaxel, Doxorubicin, Cyclophosphamide) over FAC (fluorouracil, Doxorubicin, Cyclophosphamide) in Women with Operable Node-Positive Breast Cancer
Authors: Martin M , Mackey J , Pienkowski T , Rolski J , Guastalla J-P , Sami A , Glaspy J , Juhos E , Wardley A , Fornander T , Hainsworth J , Coleman R , Modiano M , Vinholes J , Pinter T , Childs B , Roessner M , Wilson V , Rupin M , Vogel C 
Published: April 2011

Abstract
Background: The second interim analysis of the BCIRG001 trial at a median follow up of 55 months showed that adjuvant chemotherapy with TAC improves disease-free survival (DFS: HR 0.72; P=0.001) and overall survival (OS: HR 0.70; P=0.008) compared with FAC in women with operable node-positive breast cancer (N Engl J Med 2005;352:2302-13). We now report the final analysis of DFS, OS, and long-term safety after 10 years of follow-up.
Patients and Methods: Women with node-positive breast cancer were randomized to adjuvant treatment with either TAC or FAC every 3 weeks for 6 cycles. The primary end point was DFS. Secondary end points included OS and safety.
Results: Between June 1997 and June 1999, 1491 women (TAC N=745; FAC=746) from 20 countries were enrolled. Median follow up was 120 months. As of the cut-off date for this analysis (11 March 2010), there were a total of 620 DFS events (287 events with TAC; 333 with FAC). Ten-year DFS rates were 62% with TAC and 55% with FAC. TAC improved DFS irrespective of nodal status, hormone receptor status, and HER2/neu status. There have been 429 deaths (188 deaths with TAC; 241 with FAC) and 10-year OS rates were 76% with TAC and 69% with FAC. There was no statistically significant difference in rates of grade 3-4 congestive heart failure (CHF): TAC 3.5% vs FAC 2.3%, P=0.18. Deaths due to CHF have occurred in 2 patients in the TAC group and 4 patients in the FAC group. Rates of asymptomatic left ventricular dysfunction will be presented. A total of 6 patients have developed acute myeloid leukemia (TAC N=4; FAC N=2).
table 1
ITT, intention-to-treat
Conclusion: Ten-year follow up analysis of the BCIRG 001 trial confirmed that TAC significantly improves DFS and OS compared with FAC in women with node-positive early breast cancer.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-3.
Abstract S4-5: Adjuvant Treatment with Zoledronic Acid in Stage II/III Breast Cancer. The AZURE Trial (BIG 01/04)
Authors: Coleman RE , Thorpe HC , Cameron D , Dodwell D , Burkinshaw R , Keane M , Gil M , Houston SJ , Grieve RJ , Barrett-Lee PJ , Ritchie D , Davies C , Bell R. 
Published: April 2011

Abstract
Background: The ABCSG XII trial demonstrated a 32% risk reduction in disease-free survival (DFS) events with Zoledronic acid (ZOL) use in a cohort of premenopausal women treated with endocrine therapy at 62 months median follow-up .[1,2] This strategy is increasingly being adopted in the wider breast cancer population. The AZURE trial is an academic study designed to determine whether treatment with ZOL added to standard adjuvant therapy improves DFS and bone metastasis-free survival (BMFS) in a broader range of patients with stage II/III breast cancer. Materials and methods: 3360 patients from 174 centres were randomized to receive (neo) adjuvant chemotherapy (CT) and/or endocrine therapy (ET) +/− ZOL 4mg iv every 3-4 weeks for 6 doses, then 3 monthly x 8 and 6 monthly x 5 to complete 5 years treatment. The primary DFS endpoint was to be determined after 940 DFS events, providing 80% power to detect a 17% reduction in hazard rates (HR) for DFS events. The rate of events on study has been slower than expected, resulting in an estimated final analysis in 2012. In light of the clinical interest in the results of AZURE, the DMEC has agreed to a second interim analysis after 705 events with boundaries set by an independent statistician, unaware of results at the first interim analysis, for both efficacy (HR ∼0.82, alpha spend 1%) and lack of clinical benefit (HR ∼0.935 with a 5% risk of declaring a false negative result). Contingent on DMEC advice, efficacy results that breach either boundary will be presented. A DMEC recommendation not to release the results at the second interim analysis may indicate that the point HR estimate lies between these boundaries.
Results: Patient characteristics including stage, number of positive axillary nodes, CT type, ER status, menopausal status and statin use were well balanced. 3208 patients (96%) received (neo) adjuvant CT (93% anthracyclines, 23% taxanes). 152 patients received ET alone. As of June 9th 2010, with a median follow up of 49 (IQR 42-56) months, there have been 695 DFS events. The safety population comprised 3340 patients (ZOL 1665; control 1675). The addition of ZOL to standard treatment did not significantly impact on chemotherapy delivery. Serious adverse events (SAE) were similar in both treatment arms. To date 13 confirmed (0.83%; 95% CI 0.38%, 1.28%) and 12 possible (1.12%; 95% CI 0.39%, 1.85%) cases of osteonecrosis of the jaw (ONJ) in the ZOL arm have occurred. Discussion: AZURE is one of the largest phase III studies of adjuvant bisphosphonates, and the results from this study will help define the role of adjuvant ZOL in the management of early breast cancer.
[1] Gnant M et al. NEJM 2009; 360(7):679-691
[2] Gnant M et al. ASCO 2010 Proceedings; abs #533.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-5.
Abstract S4-6: Neoadjuvant Chemotherapy with or without Bevacizumab: Primary Efficacy Endpoint Analysis of the GEPARQUINTO Study (GBG 44)
Authors: von Minckwitz G , Eidtmann H , Rezai M , Fasching PA , Tesch H , Eggemann H , Schrader I , Kittel K , Hanusch C , Kreienberg R , Solbach C , Gerber B , Jackisch C , Kunz G , Blohmer J-U , Huober J , Hauschild M , Fehm T , Loibl S , Nekljudova V , Untch M. 
Published: April 2011

Abstract
Background: The anti-VEGF-receptor antibody bevacizumab (Bev) showed increased response rates and prolonged progression-free survival in combination with anthracyclines (A) and taxanes (T) in metastatic breast cancer (BC). One primary aim of the GeparQuinto phase III study was to improve pathological complete response (pCR) by adding Bev to AT-based neoadjuvant chemotherapy. We previously reported interim safety data showing more leukopenia, infections, mucositis, and hypertension, but less edema for the combination with Bev (von Minckwitz G et al, Ann Oncol 2010 in press).
Patients and Methods: Patients (P) with untreated HER2-negative BC were eligible if they had cT3/4a-d; or estrogen (ER) and progesterone (PgR) receptor-negative; or ER/PgR-positive tumors with clinically N+ (for cT2) or pNSLN+ (for cT1) disease, and no increased cardiac or bleeding risks. P were randomized to receive 4 cycles epirubicin/cyclophosphamide (EC) (90/600 mg/m2) q3w followed by 4 cycles docetaxel (D) (100mg/m2) with or without concomitant Bev 15mg/kg q3w added to chemotherapy cycles. P not clinically responding to EC ± Bev were considered as treatment failures and entered another part of the protocol. pCR was defined as no invasive or non-invasive tumor residuals in breast and nodes. We assumed a pCR rate of 14% (based on GeparDuo) and expected a pCR of 18.9% for EC-D+Bev (odds ratio 1.43). A two-sided Pearson's Chi2 with α=0.05 and β=0.20 calculated a sample size of 1934 P.
Results: Between 05/07 and 06/10 1889 P were randomized to EC-D (N=944) and EC-D+Bev (N=945). Median tumor size was 40/40 [-Bev/+Bev] mm (clinically) and 29/29 mm (sonographically); 6.3%/5.8% had T4a-c, 6.6%/6.7% T4d, 2.0%/2.1% bilateral, 14.3%/13.8% multifocal, and 8.8%/10.0% multicentric disease, 89.3%/88.9% had non-lobular, 42.5%/43.3% grade 3, 57.1%/58.4% node-positive, and 34.5%/33.6% ER and PgR-negative (triple-negative) disease. So far, 24% and 17% of patients did not respond to the first 4 cycles of EC-Bev and EC+Bev, respectively, and discontinued randomized treatment. The last randomized P will have surgery early Dec'10. Results on histological response and surgical outcome will be reported.
Conclusion: The GeparQuinto trial will provide for the first time randomized phase III efficacy data on Bev in combination to chemotherapy for patients with early breast cancer. pCR after Bev treatment can be considered as a surrogate marker for long term outcome but this has to be examined during further follow up of the patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S4-6.