bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-11-20: Open-Label Phase II Study of Neoadjuvant Bevacizumab Combined with FEC→Paclitaxel in Patients with Inflammatory or Locally Advanced Breast Cancer
Authors: Venturini M , Del Mastro L , Aitini E , Saracchini S , Garrone O , Durando A , De Placido S , Boni C , Levaggi A , Scalamogna R , Galli A , Clavarezza M. 
Published: April 2011

Abstract
Background: There is strong evidence that VEGF plays an important role in the pathogenesis and progression of human breast cancer. Bevacizumab, a monoclonal antibody, specifically inhibits VEGF. The combination of first-line bevacizumab with chemotherapy significantly improved the activity in comparison to chemotherapy alone in three randomized phase III trials in metastatic breast cancer patients (pts). In early breast cancer, the FEC→Paclitaxel regimen is a highly active standard therapy. Therefore we initiated a trial to evaluate the combination of bevacizumab with this efficacious chemotherapy regimen for the treatment of stage III or inflammatory early breast cancer (LABC).
Patients and Methods: The study is designed to evaluate a sequential regimen of FEC90 followed by the combination of paclitaxel and bevacizumab as neoadjuvant therapy in patients with HER2-negative locally advanced (stage III or inflammatory) breast cancer. Patients are treated with neoadjuvant FEC 600/90/600 mg/m2 q21d x 4, followed by paclitaxel 80 mg/m2 weekly x 12 combined with bevacizumab 10 mg/kg q2w x 6. Patients undergo surgery 4 weeks after completing chemotherapy. Pathologic complete response (pCR), the primary endpoint, is defined as no evidence of invasive tumor in the final surgical sample both in the breast and axilla. Secondary endpoints include objective clinical response rate (RR), disease-free interval, overall survival, rate of breast-conserving surgery, and the safety of the regimen.
Results: Between Feb 2008 and Dec 2009, 54 pts (mean age of 51±7.5 years) were enrolled into the study. To date, 32 pts have completed neoadjuvant treatment and surgery and are evaluable for response. Baseline characteristics in these 32 patients were as follows: cT3/cT4b: 20 (63%) and/or cN2/cN3: 14 (43%); estrogen receptor (ER) positive: 24 (75%) and 8 (25%) triple-negative (TN), defined as ER negative, progesterone receptor-(PgR-) negative, and HER2 negative. Histological type was ductal carcinoma in 24 patients (75%), lobular carcinoma in 4 (13%), inflammatory breast cancer in 1 (3%), and other in 3 (9%). Mastectomy was performed in 22 patients (69%) and breast-conserving surgery in 10 patients (31%). After neoadjuvant treatment, 8/32 patients (25%) achieved a pCR.
Conclusions: This open-label, multicenter, phase II study demonstrated that the FEC→Paclitaxel plus bevacizumab combination is a highly active neoadjuvant treatment for HER2-negative locally advanced breast cancer. A 25% of pCR in this group of pts with high tumor burden, i.e. the LABC, is oneof the most promising chemotherapeutic regimen if confirmed in the final analyis. Results for all 54 pts enrolled will be presented at the meeting.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-20.
Abstract P1-12-03: The STAGE Study: A Phase III Comparison of Anastrozole Plus Goserelin with Tamoxifen Plus Goserelin as Pre-Operative Treatments in Premenopausal Breast Cancer Patients
Authors: Sagara Y , Masuda N , Kinoshita T , Iwata H , Nakamura S , Yanagita Y , Nishimura R , Iwase H , Kamigaki S , Takei H , Noguchi S. 
Published: April 2011

Abstract
Background: Although superior antitumor activity of anastrozole over tamoxifen has been well established in postmenopausal breast cancer patients, it still remains to be examined whether or not anastrozole is superior to tamoxifen in premenopausal breast cancer patients whose ovarian function is suppressed by goserelin to postmenopausal levels. The aim of this study was to compare anastrozole plus goserelin versus tamoxifen plus goserelin as pre-operative treatment for premenopausal Japanese women with breast cancer.
Methods: Phase III, randomized, double-blind, parallel-group, multi-center study (D539BC00001). Premenopausal patients (pts) with ER-positive and HER2-negative breast cancer and with operable and measurable lesions (T [2-5 cm], N0, M0) were randomized 1:1 to receive a goserelin 3.6 mg depot injection once monthly plus either anastrozole 1 mg (A+G) or tamoxifen 20 mg (T+G) p.o. once daily. Treatment continued for 24 weeks prior to surgery or until any other criterion for discontinuation was met. Concomitant chemotherapy was not permitted during the pre-operative period. The primary objective was to assess the best overall tumor response (either a complete response [CR] or a partial response [PR]), according to modified RECIST criteria. Tumor size was measured by caliper and ultrasound every 4 weeks and by magnetic resonance imaging/computed tomography (MRI/CT) every 12 weeks. Tolerability (adverse events [AEs], laboratory tests, vital signs, WHO performance status) was assessed as a secondary objective. AEs were evaluated according to CTCAE v3.0.
Results: In total, 197 pts were randomized (A+G: 98, T+G: 99) and 185 pts completed the 24-week pre-operative treatment period and went on to receive breast surgery. The remaining 12 pts discontinued study treatment due to disease progression (A+G: 1; T+G: 5), voluntary discontinuation (A+G: 2; T+G: 3) and AE (T+G: 1). Pt demographics were generally well balanced. Median duration of exposure was similar for A+G (171 days) and T+G (170 days); treatment compliance was 99% for both. A+G led to a statistically significantly higher overall response rate compared with T+G, by caliper as well as by ultrasound and MRI/CT.
The safety profiles were consistent with the known safety profile of anastrozole, tamoxifen and goserelin. The incidence of AEs was similar
for A+G (88.8%) vs T+G (85.7%); most AEs were mild or moderate (CTC grade 1 or 2). The most common AEs were hot flash (A+G: 52.0%; T+G: 53.1%) and arthralgia (A+G: 35.7%; T+G: 20.4%). Conclusion: This study has demonstrated that the A+G combination has a superior benefit-risk profile compared with T+G as pre-operative treatment in Japanese premenopausal women with ER-positive breast cancer.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-03.
Abstract P1-12-05: Factors Affecting Local Recurrence after Breast Conserving Surgery Following Neoadjuvant Endocrine Therapy with Letrozole
Authors: Dixon JMJ , Renshaw L , Keys J , Leeper AD , Williams L , Evans DB. 
Published: April 2011

Abstract
Background
Few data exist on local recurrence rates after breast conserving surgery in post menopausal patients following neoadjuvant endocrine therapy with letrozole. The aim was to investigate the outcome of a large series of patients treated in the Edinburgh Breast Unit. Patients
208 patients underwent breast conserving surgery after at least a 3 month course of neoadjuvant letrozole. The median age was 77 years (range 51 to 93). Of these patients 73% (151/208) received postoperative radiotherapy.
Median follow up was 2.95 years (range 0.28 to 8.43)
Results
At two years 97% were local recurrence free and by five years 95% were recurrence free. By the Log Rank (Mantel-Cox) non-parametric method of analysis, there was a significant difference between patients treated by postoperative whole breast radiotherapy (RT) compared with no radiotherapy (p=0.02). There were very small numbers of local recurrences (five in no RT group, two in RT group by the end of five years). At two years 93% of patients with no RT were recurrence-free, compared with 98% of those with RT, at five years this is 86% and 98% respectively There was a borderline significant difference between HER2 positive and negative breast cancers, (p=0.055). At two years 97% of HER2 negative patients were recurrence-free, compared with 91% of HER2 positive patients. At five years, it was 96% and 85% respectively. Death from other causes was very common in this elderly age group and the median survival time was 7.2 years (95% CI 5.8 to 8.5). 90% of patients survived to the end of two years (95% CI: 86% to 94%), while only 68% survived to the end of years (60% to 76%).
By the Log Rank test, there was a significant difference between patients treated by radiotherapy and those who did not receive radiotherapy (p=0.004). The median survival with no RT was 4.7 years (95% CI: 3.7 to 5.8) and for patients following RT was 8.1 years (95% CI: 6.2 to 10.0). The reason for this was selection of fitter patients for radiotherapy and avoiding radiotherapy in frail patients.
Conclusions
Local recurrence after breast conserving therapy following neoadjuvant endocrine therapy with letrozole is uncommon in this group of patients. Following radiotherapy local recurrence is only 2% at 5 years. Rates of recurrence are over 10% at 5 years without radiotherapy. HER2 positive patients have a higher local recurrence rate than HER2 negative patients.
Breast Conserving Surgery followed by whole breast radiotherapy produces excellent rates of local control in postmenopausal women following neoadjuvant endocrine therapy with letrozole.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-05.
Abstract P1-12-07: Neo-Adjuvant Exemestane in Post Menopausal Estrogen and/or Progesterone Receptor Positive Breast Cancer: A Randomized Phase II Trial To Investigate Optimal Duration (4 Month Versus 6 Month) of Preoperative Endocrine Therapy (PTEX46 Trial)
Authors: Hojo T , Kinoshita T , Wada N , Imoto S , Tamura N , Nagao T , Ando M , Katsumata N , Fujiwara Y. 
Published: April 2011

Abstract
Background: Since the 1990s, primary endocrine therapy has been considered the gold standard in the adjuvant and metastatic treatment settings for estrogen and/or progesterone receptor (ER and/or PgR) positive breast cancer. This therapy has also been shown to be effective as neo-adjuvant endocrine therapy in these indications. In recent years, the focus of clinical interest has shifted to the third-generation aromatase inhibitors from tamoxifen. The optimal treatment duration time and causal relationship between neo-adjuvant endocrine therapy and survival, however, are not clear. We therefore conducted the present study to investigate the potential benefits of neo-adjuvant exemestane (E) therapy with the goal of identifying the optimal treatment duration (4 months versus 6 months).
Methods: Conducted at three hospitals in Japan, this study was a multicenter, randomized phase II trial of pre-operative E treatment in postmenopausal women with untreated primary breast cancer. Fifty postmenopausal women with ER positive and/or PgR positive invasive breast cancer were randomly assigned to E (25 mg/day) for 4 months (4 mo) or E (25 mg/day) for 6 months (6 mo). All patient data were collected by UMIN and were analyzed by the National Cancer Center in Japan. Tumor regression (by clinical examination, ultrasound, and MRI), pathological response, shift towards breast-conserving surgery, and safety assessments were the main outcome measures.
Results: Of the 50 patients that enrolled, 28 patients had undergone surgery. The mean ages in the 4 mo and 6 mo treatment groups were 66.7 years and 66.8 years, respectively. No significant differences in the patient characteristics were found in the two groups. The response rates (partial or complete responses) by clinical examination in the 4 mo and 6 mo groups were 37.5% and 50%, respectively. Pathological responses (minimal response or better) were found in 13.3% and 41.7% of patients and a partial mastectomy was performed in 50.0% and 58.3% of patients after 4 mo and 6 mo, respectively.
Conclusion: To date, the results of this study demonstrate that treatment with E for 6 mo was more efficacious than treatment with E for 4 mo. Further work is in progress to obtain data from additional patients and to identify the optimal duration of neo-adjuvant E.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-07.
Abstract P1-13-01: Comparing the Effects of Denosumab and Zoledronic Acid on Pain Interference with Daily Functioning in a Randomized Phase 3 Trial of Patients with Breast Cancer and Bone Metastases
Authors: Cleeland CS , Patrick DL , Fallowfield L , Clemons M , Lipton A , Masuda N , Qian Y , Braun A , Chung K. 
Published: April 2011

Abstract
In a recently completed trial of breast cancer patients with bone metastases, denosumab, a fully human monoclonal anti-RANKL antibody, was superior to zoledronic acid (ZA) in delaying/preventing skeletal-related events. Between-treatment differences in patient-reported pain interference with daily functioning were assessed.
Eligible breast cancer patients received monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg (double-bind, double-dummy design). Patients completed the Brief Pain Inventory (BPI) to assess pain severity and interference with daily functioning (range 0 [does not interfere]-10 [interferes completely]) at baseline (BL), day 8, and before each monthly visit through end of study. The BPI interference scale generated a total interference score as well as an activity subscale (interference with walking, general activity, and work) and an affective subscale (interference with relations with others, enjoyment of life, and mood). Analyses were conducted on all randomized patients with ≥1 PRO assessment and were performed through week 73, when 30% of patients had dropped out due to death, disease progression, or consent withdrawal. Subgroups included patients with no/mild and moderate/severe worst pain at BL. Analyses included time to improvement (≥2-point decrease) or worsening (≥2-point increase) in pain interference, mean change from baseline, and proportion of patients with improving or worsening pain interference scores. Time to improvement in pain interference with activity (PIWA) tended to occur more quickly with denosumab compared with ZA (N=1124; median: 70 days denosumab v 86 days ZA; P=0.09), and time to worsening PIWA tended to be longer with denosumab compared with ZA (N=1676; median: 394 days denosumab v 310 days ZA; P=0.13). In patients with no/mild pain at BL, denosumab also demonstrated a trend for shorter time to improvement in PIWA (N=388; 93 days denosumab v 120 days ZA; P=0.06) and longer time to worsening PIWA (N=755; 369 days denosumab v 232 days ZA; P=0.12). Overall, a greater proportion of patients on denosumab had improvement in PIWA on study than ZA (Figure). Findings were similar with the total interference score and affective subscale.
Figure Proportion of Patients With Improvement in Pain Interference With Activity (≥2-point decrease from BL)*
Daily functioning (total interference and interference with activity and affect) tended to be less disrupted by pain in patients on denosumab compared with ZA. Decreased pain interference showed a trend to occur more quickly with denosumab. Overall, a greater proportion of denosumab patients reported decreased pain interference than ZA patients.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-01.
Abstract P1-13-04: Immunohistochemical Evaluation of RANK/RANKL/OPG Axis and CXCR4 in Primary Breast Cancer and Their Role in Bone Metastasization
Authors: Ibrahim T , Sacanna E , Gaudio M , Mercatali L , Ricci R , Scarpi E , Serra P , Fabbri F , Serra L , Amadori D. 
Published: April 2011

Abstract
Background: The RANK/RANKL/OPG axis plays an important role in the bone metastasization process. CXCL12 is overexpressed in bone and, like its receptor, CXCR4, is a determinant of organ tropism. The objective of the present study was to evaluate whether the expression of these markers in primary breast cancer can predict the onset of bone metastases. Methods: Marker expression was evaluated by immunohistochemical staining in paraffin-embedded sections of primary breast cancers from 40 individuals: 10 patients (median age 64 years, range 48-78) showed no evidence of disease (NED — control group) at a median of 9.8 (range 6.9-11.5) years, while 30 (median age 67 years, range 42-87) had relapsed. In the latter group, 10 (median age 66 years, range 42-87) had visceral metastases (VM — control group) and 20 (median age 69 years, range 42-87) had bone metastases (BM — case group), both confirmed radiologically. The 3 patient subgroups (NED, visceral lesions, bone lesions) were matched for age classes (≥60 years, &gt; 60 years). The study design was reviewed and approved by the local ethics committee.
Results: In the overall series, 17.5% of tumors were positive for RANK, 22.5% for OPG and 25% for CXCR4. None of the patients expressed RANKL. RANK and OPG resulted equally expressed in 20% of NED patients, while CXCR4 was expressed in only 10% of this group. OPG was expressed in 20% of VM patients, whereas RANK or CXCR4 were not detected. RANK and OPG positivity was present in 25% of BM patients, while CXCR4 was expressed in 45% of cases. CXCR4 was the only marker with a significantly higher frequency of expression in bone metastases than in visceral lesions (p=0.013). Taking into consideration all the patients without bone involvement (NED plus VM patients), it was observed that CXCR4 expression, alone and in combination with RANK, significantly discriminated between BM patients and the control group (p=0.008 and P&lt;0.001, respectively). ER-positivity and HER2-negative status were observed in 80% and 95% of BM patients, respectively, but neither discriminated between cases and controls. Conclusions: In our study, ER-positivity and HER2- negativity identified a high percentage of bone relapse patients, but also highlighted patients who did not have bone involvement. RANK and CXCR4 expression, on the other hand, would appear to be a more accurate predictor of bone relapse. Such evidence could help to identify patients with a high probability of developing bone metastases, which can be treated with bisphosphonates or other bone-targeted therapies, such as denosumab, in an attempt to prevent distant metastases. Our results are currently being validated in a larger series of breast cancer patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-04.
Abstract P1-13-06: Health Resource Utilization Associated with Skeletal-Related Events in Patients with Bone Metastases: Interim Analysis Results from the US Breast Cancer Cohort of a Multinational Observational Study
Authors: Mahmood A , Robles R , Ghazal H , Atchison C , Wei R , Chung K , Pinzone J. 
Published: April 2011

Abstract
Background: Bone metastases are common in women with advanced breast cancer and are frequently associated with skeletal-related events (SREs). The burden of individual SRE types on health resource utilization (HRU) indicators in breast cancer has been only minimally described. Methods: The aim of this ongoing observational, prospective, multinational study is to assess, by tumor type, the amount of HRU associated with different SRE types including pathologic fracture, surgery or radiation to bone, and spinal cord compression. Patients with breast, prostate, or lung cancer and bone metastases or multiple myeloma were enrolled after experiencing a SRE. Inpatient hospitalizations, length of stay, outpatient visits, emergency room visits, nursing home/long-term care facility stays, home health visits, procedures, and medications were collected for the period 90 days prior to enrollment and prospectively to a maximum of 18 months. Each patient could contribute multiple SREs. The investigator determined which HRU were attributed to each SRE. This abstract describes interim analysis data from the US breast cancer cohort; final analysis data will be available 9/2010.
Results: As of 12/1/2009, 67 patients contributed 119 SREs for the HRU analyses across 25 US sites. Patient mean [SD] age was 61 [12] years, all patients were female, and 27% discontinued the study (most due to death). Mean duration of follow-up was 9.9 months. HRU for each of the SRE types are shown in the table.
Table. Mean and median number of HRU per SRE during the study period by SRE type in patients with breast cancer
Conclusion: In this interim analysis of advanced breast cancer patients in the US, SREs are associated with considerable HRU, with the nature and extent of HRU varying depending on the SRE type.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-06.
Abstract P1-13-07: Standardized Immunocytological and Molecular Analysis of Tumor Cells and Mesenchymal Stromal Cells in Bone Marrow of Patients with Primary Breast Cancer
Authors: Sonnauer M , Kaul S , Fersis N 
Published: April 2011

Abstract
Background: Using criteria for classification of disseminated tumor cells in compliance with the publication of Fehm et al. (Cancer, Vol.107, 2006) we have reported a cytological DTC-positivity rate of 1.9% (39/2050) in patients with primary breast cancer (T1-4, N0/N+, M0/M1). However automated picture analysis revealed cytokeratin positive stroma cell types in DTC negative samples. Here we describe the cytological and molecular characterization of these mesenchymal stromal cell (MSC) types. Material and Methods: Mononuclear cells were enriched by Ficoll density-gradient centrifugation. Cytospin slides (mean 6) with 1x106 BM-cells were stained by CK antibodies 5D3 and A45-B/B3 using automated immunostainers with the APAAP-and the enhanced SA-FastRed-method. Slides were analysed by automated picture analysis with the ACIS I and ACIS II systems (ChromaVision). Plastic adherent cells (1x106) from culture passage one from 71 breast cancer patients were analysed for expression of CK19, MUC1 and EpCAM by FACS analysis. Trypsinized cells (n=100) were lysed and used for mRNA isolation and c-DNA synthesis (Qiagen®). A real-time quantitative RT-PCR approach (MESA FAST SYBR Assay, Eurogentec®) and primers selected from the UniversalProbeLibrary system (Roche AG®) was used for the determination of the markers EpCAM, survivin, CD144, CD146, CD 105, and CD271.
Results: Small cells characterized by an excentrically located small and clear nucleus were detected in 56% (486/866) of the bone marrow samples in a mean frequency of 1-2 cells per slide. However a subgroup of patients is characterized by elevated MSC levels. More than 5 MSC cells per 106 BM cells were detected in 19,7% (96/486) samples of the DTC negative group with elevated MSC levels in 5,2% NO, 6% N+ and 9% T3/T4 tumors. By molecular expression analysis of 71 bone marrow samples 8 probes (11%) were CK19 positive. Corresponding MSC cultures had significantly elevated expression levels of the markers vimentin, survivin, CD144, CD105, CD146 and CD271.
Discussion: We have identified CK positive bone marrow stroma cells in 56% of patients with primary breast cancer. Immunobead RT-PCR based on 107 BM cells can be used to eliminate this background and to increase DTC-sensitivity from 2 to 11%. Frequency and expression profile of MSC in these probes may give valuable additional information to understand in the complex interrelation of tumor cells with tumor-associated mesenchymal stromal cells, erythroblasts and endothelial cells in the process of metastasis.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-07.