bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-10-09: Access to HER2 Testing in Early Stage Breast Cancer (ESBC) in a Single Payor, Public Healthcare System — Ontario (ON), Canada
Authors: Ferrusi IL , Trudeau M , Earle C , Leighl NB , Pullenayegum E , Cascagnette P , Marshall DA. 
Published: April 2011

Abstract
Background: In ON, testing for HER2 overexpression in ESBC was approved, along with trastuzumab (T) treatment with chemotherapy for HER2 positive (IHC = 3 or FISH ≥2.0) tumors in 2005. Guidelines for testing and treatment must be met for provincial T reimbursement. To study adherence to HER2 testing and T utilization guidelines in ESBC, we first describe patient access to HER2 testing by age, tumor, stage, urbanicity and income. Methods: A population-based retrospective cohort of ESBC patients diagnosed in 2006 and 2007 was identified using the Ontario Cancer Registry and for whom ≥1 pathology report was available from Cancer Care Ontario (CCO). All BC-related pathology reports were individually reviewed to identify early stage, resected, primary BC. Information was collected on surgical procedure, TN stage, histologic grade, receptor status (ER/PR) and HER2 test provision. Linkage to other administrative databases provided income quintile, urban vs. rural residence and institution of diagnosis. Odds ratios were calculated to determine association of HER2 testing with any pathologic or socioeconomic factors. Results: The 2-year cohort contains 13,430 ESBC patients, 60% of which had breast conserving surgery. 29,746 (2.2/patient) pathology reports were reviewed. 13% of the cohort had rural residences, and 95% were alive at end of follow-up. Age at diagnosis was distributed as: 5% &lt; 40 years, 18% 40-49 years, 25% 50-59 years, 24% 60- 69 years, 18% 70-79 years and 10% ≥80 years. Stage at diagnosis was: 35% stage I, 32% stage II, 10% stage III and 22% stage unknown after removing all stage IV. No differences in HER2 testing were observed for patients across income quintiles (P&gt;0.3550). Patients ≥80 years (P&lt;0.0001) and &lt;40 years (p=0.0074) had significantly lower odds of receiving ≥1 HER2 test than patients 40-49 years. ESBC of higher histologic grade had significantly greater odds (P&lt;0.0001) of ≥1 HER2 test compared to grade I ESBC. Patients from rural areas had lower odds of HER2 testing compared to urban patients (P&lt;0.0001). Conclusions: For the 2 years 2006-2007: 13,430 ESBC patients were identified from the OCR for which ≥1 pathology report was available from CCO. Age, stage at diagnosis, and surgical procedure were representative of an ESBC population. HER2 testing was universally available per Ontario policy, but not all reports were submitted to CCO. The odds of having a documented HER2 test were not affected by income, but testing was more likely to be documented for high grade tumours and less likely to be documented for the youngest and oldest women and those with rural residence. Pathology reports missing from CCO are being sought. Adherence to guidelines for testing, treatment with T and cardiac monitoring during treatment will be assessed.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-10-09.
Abstract P1-11-04: A Phase II Preoperative Trial of Concurrent Trastuzumab and Paclitaxel without Anthracycline in HER2-Positive Operable Breast Cancer
Authors: Sato T , Hayashida T , Takahashi M , Sakata M , Jinno H , Hirose S , Mukai M , Kitagawa Y. 
Published: April 2011

Abstract
Background
Concurrent trastuzumab with paclitaxel/fluorouracil, epirubicin, and cyclophosphamide (P/FEC) chemotherapy as neoadjuvant treatment revealed the high pathologic complete response (pCR) rate of 54.5% (Buzdar, 2007). Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway either through loss of PTEN or mutation of the catalytic subunit alpha of PI3K (PIK3CA) might confer resistance to trastuzumab. The objective of this study was to determine the efficacy of concurrent administration of trastuzumab and paclitaxel wtihout anthracycline as preoperative chemotherapy. The correlation between deregulation of PI3K and resistance to trastuzumab was also investigated. Patients & methods
Patients with HER2-positive, operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2) and trastuzumab (4mg/kg loading dose then 2 mg/kg) for 12 weeks before surgery. PTEN status was evaluated by immunohistochemistry. PTEN staining intensity scores was recorded on an integer scale from 0 to 2+ (0; no staining, 1+; reduced staining, and 2+; equal staining as compared to the internal control). Sequencing of PIK3CA exons 9 and 20 was done by PCR amplification and direct sequencing. pCR was defined as no residual invasive carcinoma in the breast. Results
Twenty-eight patients were enrolled and assessable for clinical and pathologic responses. The overall response rate was 92.9%, including a complete response in 13 patients and a partial response in 13 patients. The pCR rate was 53.6% (15/28). Twenty-three patients (82.1%) underwent breast concerving surgery. Progesteron receptor (PgR) status was significantly correlated with pCR (p=0.025). Eight of 24 patients (33.3%) were scored PTEN negative. PIK3CA mutations were identified in 4 of 13 patients (30.8%). There was no significant difference in pCR rate and PTEN loss/PIK3CA mutation.
Correlation of PgR status and pCR
Conclusions
These data indicate that the combination of trastuzumab and paclitaxel without anthracycline is effective preoperative chemotherapy with high pCR rate. PTEN loss and/or PIK3CA mutation were not useful predictors of resistance to trastuzumab.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-04.
Abstract P1-11-08: A Multicenter Prospective Phase II Trial of Neo-Adjuvant (FEC 100)/Cisplatin-Docetaxel with or without Trastuzumab in Locally Advanced Breast Cancer. Gulf Oncology Research Group (G0RG-001)
Authors: AL-Tweigeri TA , Alsayed AA , Ibrahim MM , Ashaur WM , Jaafar HN , Abulkhair OA , Al-Abdulkarim HA , Khalid HKH , Alawadi SA , Ajarim DS. 
Published: April 2011

Abstract
BACKGROUND: To evaluate the efficacy and safety profile of the (FEC100) followed by cisplatin/docetaxel with or without trastuzumab as primary chemotherapy for patients with locally advanced breast cancer (LABC T2&gt; 4cm, N0-2, M0).
METHODS: Eighty (80) patients with LABC (T2-T4, No-N2, M0) received 4 cycles of FEC (100) followed by 4 cycles of cisplatin/docetaxel, followed by definitive surgery and locoregional radiotherapy with or without hormonal therapy. Patients with HER2 positive received trastuzumab concurrently with cisplatin docetaxel for a total of 8 cycles (for a total of 6 months). The primary end point was pathologic complete response (pCR) in breast and/or axilla for HER2 negative and HER2 positive. RESULTS: Seventy nine (79) patients were evaluable for analysis: median age: 43yrs, Premenopausal: 83%, median tumor size: 7.0cm (≥4 - 10), Stage IIB: 24% and IIIA/IIIB: 76%, both ER/PR positive: 56%, Her2/neu (3+) by IHC staining: 39%. Clinical response was 65% complete response and 28% partial response. Breast conserving surgery was performed in: 10 % and MRM in: 90%.Three (3) patients suffered an asymptomatic and reversible decrease in left ventricular ejection fraction. Pathological complete response (pCR) can b summarized as follow: Overall pCR in breast: 37%, in Axilla: 65%, Breast and axilla: 33%. In patients with HER2 Negative: pCR in breast: 19%, in Axilla: 56%, Breast and axilla: 17%.In patients with HER2 positive: pCR in breast: 65%, in Axilla: 77%, Breast and axilla: 58%.Overall the DFS & OS at 3 years were 88% and 98% respectively.
CONCLUSIONS: This sequential combination is a safe, feasible and active combination, which associated with high clinical and pathologic response rates, the addition of trastuzumab increased pCR rate in HER2 positive tumors with promising and encouraging outcomes, further investigation of this combination are warranted.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-08.
Abstract P1-11-09: Predictive Response Factors (PRF) in an Open, Non-Randomized, Phase II Study of a Combination of Bevacizumab (BZ) and Sequential Chemotherapy as Preoperative Treatment in Patients with Operable HER-2 Negative Breast Cancer (BC)
Authors: Sanchez Rovira P , de la Haba J , Fernandez M , Segui MA , Llombart A , Anton A , Sanchez A , Aranda E. 
Published: April 2011

Abstract
Introduction: Association of BZ to chemotherapy in BC improves time to progression of advanced disease. However limited studies are still available for primary treatment, and PRF are not still clearly determined, above all in HER-2 negative patient subgroup receiving antiangiogenic therapy. Objetives: To determine percentage of pathological Complete Responses (pCR) in patients diagnosed of locally advanced BC who receive neoadjuvant sequential therapy in association with BZ, as well as to determine the PRF and perform differential analysis of treatment resistant genes.
Material/Methods: 72 patients were included in ML20382 clinical trial. Treatment was 4 cycles of doxorubicin/cyclophosphamide 60/600 mg/m2 x 21 days, followed by 4 cycles of BZ 15 mg/kg + docetaxel 75 mg/m2 x 21 days. Median age was 46 years. Stage classification was 20.8% IIA, 43.1% IIB, 23.6% IIIA, 8.3% IIIB, 4.2% IIIC. Median tumor size was 4.75 cm. 68.1% showed axillary affectation and 80.6% were hormone-receptor positive. Clinical evaluation was done by mammography and mammary ultrasound and/or NMR. Tumor samples were collected before treatment and after surgery for analysis of VEGF, VEGFR, EGFR, pAKT, pMAPK, pTEN, HIF, IGF and differential analysis of gene expresion.
Results: 66 patinets evaluated for histopathological response, resulting in 24. 2% of pCR (CI 95%, 14.5-36.4). Multivariate analysis shows a significant increase of responses in ER-negative patients. Treatment was well tolerated, with haematological toxicity G3-4 for 22% of patients (12.5% of neutropenic fever as most noteworthy toxicities). Most relevant non-haematologycal toxicity was mucositis G3 for 19.4% and hypertension for 1.4%. Preliminary analysis shows VEGFr and KISS1 amplification entail a tendency of a lower pCR rate (8.7% and 6.25% respectively).
Conclusions: Addition of BZ in preoperative treatment (AC+D) permits a high pCR rate with an adequate safety profile in a subgroup with a median of T&gt;4cm and predominantly ER+. Definitive results about amplification analysis of KISS1, VEGFR and Angiotensin 1 Rc, RNA and proteonomic expression will be presented.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-09.
Abstract P1-11-19: Prognostic Significance of Ki67 Index after Neoadjuvant Chemotherapy for Human Breast Cancer
Authors: Tanei T , Shimomura A , Shimazu K , Nakayama T , Kim SJ , Tamaki Y , Noguchi S. 
Published: April 2011

Abstract
Purpose: The Ki67 index (cell proliferation marker) has recently been attracting considerable attention as a prognostic factor in breast cancer, but the prognostic significance of Ki67 after neoadjuvant chemotherapy (NAC) has hardly been studied.
Experimental Design: Primary breast cancer patients (n=102) treated with NAC (sequential paclitaxel 12 cycles (q1w) and 5-FU/epirubicin/cyclophosphamide 4 cycles (q3w)) were recruited for this study. In the patients who did not achieve pathological complete response (pCR) after NAC. we evaluated the expression of Ki67, estrogen receptor (ER), progesterone receptor (PR), breast cancer resistant protein (BCRP) and P-glycoprotein were determined by immunohistochemistry, and HER2 was determined by FISH in tumor tissues obtained before and after NAC. Therefore the association of these proteins with patient prognosis (relapse-free survival) was examined.
Results: pCR was achieved in 30 (29.4%) of the 102 patients. In the remaining 72 non-pCR patients, the Ki67 index significantly (P&lt;0.001) decreased after NAC, and the Ki67 index after but not before NAC, was significantly associated with patient prognosis (P=0.022). Multivariate analysis showed that the Ki67 index after NAC was a marginally significant (P=0.05) prognostic factor and that other biomarkers including ER, PR, BCRP, and P-glycoprotein either before or after NAC were not significant.
Conclusions: Ki67 after but not before NAC, is prognostic for breast cancer patients, and may be clinically useful for the prediction of prognosis for patients who do not achieve pCR after NAC. On the other hand, BCRP and P-glycoprotein either before or after NAC are unlikely to be useful as prognostic factors for such patients.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-19.
Abstract P1-11-21: Effectiveness Analysis of Neoadjuvant Treatment by Using 4FE100C vs 6FE100C in Patients with Advanced Breast Cancer
Authors: Ramirez-Torres N , Perez-Puentes A , Astudillo-de la Vega H 
Published: April 2011

Abstract
Objective: To detect the difference in the effectiveness of 6 FE100C as neoadjuvant chemotherapy (NCT) vs 4 FE100C and set the duration.
Method. Forty-eight consecutive cases per group from January 2003 to December 2007 were registered. Patients received cyclophosphamide 500 mg/m2, epirubicin 100 mg/m2 and 5-fluorouracil 500 mg/m2 (FE100C) with 4 or 6 cycles every 21 days. They were followed by surgery and radiotherapy.
Results In the analysis, the number of the largest cycle was a predictor in clinical response. Theobjective complete clinical and partial response (cCR+cPR) was 62.5% and 87.5% with 4 FE100C and 6 FE100C respectively (p &lt;0.003); the clinical benefit was better with six FE100C with a complete response rate (cCR) of 35.4% (CI 95%: 22% −48%, n=17). The distribution of best complete pathologic response (CPR) for 6 FE100C was significantly better than for 4 FE100C (20.8% vs.12.5%, p = 0.044). The most clinically important difference in gastrointestinal toxicity caused by 6 FE100C was the effect of mild to moderate vomiting (52.4% vs. 39% for 4 FE100C, p = 0.001); the severe leukopenia (2.43% vs. 1.56%, p= 0.401) and moderate anemia (2.08% vs. 0.52%, p = 0.142) for 6 FE100C and 4 FE100C respectively. There was no significant difference between regimens. The toxicity of the nausea, alopecia and hematologic toxicity in the effect of peripheral leukocyte count and platelet presented no significant difference between regimens. The moderate anemia was rescued with blood transfusion and severe leukopenia with filgastrim. There was no cardio toxicity, thrombocytopenia or other serious events.
Conclusion: Both regimens were similar for the incidence of gastric toxicity and hematologic toxicity. The scheme of six FE100C was well tolerated in patients with LABC. It was confirmed a significant improvement in the pCR and cCR with intensified epirubicin dose (100mg/m2) for 6 cycles without granulocyte colony-stimulating factor.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-21.
Abstract P1-11-22: Bisphosphonates and Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer
Authors: Chavez-Mac Gregor M , Brown EN , Lei X , Hsu L , Meric-Bernstam F , Litton J , Mittendorf EA , Valero V , Hortobagyi GN , Gonzalez-Angulo AM. 
Published: April 2011

Abstract
Purpose: Several studies have suggested that bisphosphonates have antitumor effects and that their use may have a potential benefit on recurrence and survival in patients with primary breast cancer. In a retrospective study, we sought to evaluate whether the use of bisphosphonates increased the rates of pathological complete response (pCR) in breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy. Methods: We identified from our database 1449 breast cancer patients receiving taxane and anthracycline-based neoadjuvant chemotherapy between 1995 and 2007 at M.D. Anderson Cancer Center. Among the entire cohort, we identified by chart review those patients that while receiving chemotherapy also received bisphosphonates for a different indication (osteopenia or osteoporosis). Primary outcome was the proportion of patients achieving a pCR. Groups were compared using the chi-squared test. A multivariable logistic regression model was fit to examine the relationship between the use of bisphosphonates and pCR. An exploratory survival analysis using the Kaplan-Meier method was performed; groups were compared using the log-rank test.
Results: From the 1449 patients included, 39 (2.7%) received bisphosphonates at the time of neoadjuvant chemotherapy.66.7% received alendronate, 28.2% risedronate and 5.1% ibandronate. Those receiving bisphosphonates were older (P&lt;.001) and less likely to be obese (P=.04). The pCR rate was 26% in the bisphosphonate group and 16% in the non- bisphosphonate group (P=.11). After adjusting for potential confounding variables, patients treated with bisphosphonates tended to have higher rates of pCR (OR 2.16 95% CI 0.89-5.25); however the difference did not reach statistical significance. With a median follow up of 55 months (3-145) there were 412 recurrences and 359 deaths. There were no differences on 5-year PFS (71% vs 80%; P=.28) or 5-year OS (77% vs 82%; P=.42) between the two groups.
Conclusions: In this cohort of patients, the concurrent use of bisphosphonates at the time of neoadjuvant chemotherapy was not associated with significant increased rates of pCR. The observed estimates suggest a positive effect; however, it is possible that the small proportion of patients receiving bisphosphonates affected the power to detect a statistically significant difference. To fully test the hypothesis, additional, well-powered prospective studies to evaluate the potential use of bisphosphonates as antitumor agents used in the neoadjuvant setting are warranted.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-11-22.
Abstract P1-13-08: A Cross-Sectional Study Evaluating Bone Quantity and Quality in Women with Bone Metastases from Breast Cancer
Authors: Freedman OC , Amir E , Cheung AM , Hu H , Lee E , Dranitsaris G , Clemons MJ. 
Published: April 2011

Abstract
Background: Approximately 1/3 of patients with metastatic breast cancer (MBC) and bone disease will sustain a skeletal related event (SRE) despite use of a bisphosphonate; there is therefore an urgent unmet need in this large population to better assess individual SRE risk and develop more effective bone protective agents. Using novel tools to assess bone quality may help guide individual patient treatment choices as well as future trial design.
Materials and Methods: Women with MBC and bone metastases were recruited. Baseline bone assessments were performed using dual-energy X-ray absorptiometry (DXA) [areal bone mineral density (BMD) and vertebral fracture assessment (VFA)], high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum markers of bone turnover [serum CTX and bone-specific alkaline phosphatase (BAP)]. Risk factors for osteoporosis and fractures were then recorded. Results: 49 baseline assessments were completed. Mean age and body mass index were 53.6 (range 30-80) and 27 (range 17-45) respectively. One in four women had an ECOG 2-3, and 24% had a clinical fracture since the diagnosis of MBC. 94% had estrogen positive disease, 11% were HER2+. 53% had prior radiation therapy to bone; 90% received bisphosphonate therapy. Bone assessments are outlined in the Table. Vertebral compression deformity (VCD) using the novel technique of VFA was most strongly associated with clinical fracture (p = 0.003).
Discussion: Prospective evaluation of individual SRE risk will enable improved patient-centred care and allow more rational use of bone targeted therapies. VFA is a novel tool that may better inform treatment decisions and choice of agents in women with MBC. Future follow-up of these patients will help determine the optimal assessment modality.
Bone quantity and quality assessments

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-08.
Abstract P1-13-09: Marked Inhibition of Both Invasion and Proliferation by Zoledronic Acid and the Epidermal Growth Factor Receptor Inhibitor Gefitinib in a Bone-Seeking Clone of Breast Cancer
Authors: Oda M , Iwaya K , Yamada K , Kaise H , Ogata A , Kimura F , Kobayashi T , Matsubara O , Yoneda T , Kouno N. 
Published: April 2011

Abstract
Background: Zoledronic acid (Zol) is the most potent inhibitor of bone resorption in bisphosphonates. In order to examine whether the inhibitory effect is involved in the mechanism of bone metastasis in breast cancer, a bone-seeking clone was examined. It was established by repeated sequential passages of metastatic cells from bone in nude mice and in vitro, and it exclusively metastasizes to bone with larger osteolytic lesions than MDA-MB-231 parental cells. Recent findings indicate that epidermal growth factor (EGF) signaling is also an important mediator of bone metastasis. We examined the synergistic effects of gefitinib on the proliferation and invasion of a bone-seeking clone compared with MDA-MB-231. Materials and Methods: The cellular proliferation was estimated using WST-1. Migration in the matrigel in a Boyden chamber was applied to the invasion assay.
Results: Treatment with 1 µM of Zol reduced 51% of cell proliferation in the bone-seeking clone; however, the inhibited rate was 37% in MDA-MB-231. The migration was also inhibited with 10 µM of Zol (bone-seeking clone: 69% reduction, MDA-MB-231: 54% reduction). The reduction rates of both assays by Zol treatment were significantly higher in the bone-seeking clone than in MDA-MB-231. Treatment with 10 µM of Zol plus 1 µM of gefitinib resulted in a proliferation reduction rate of 27% compared to that with 10 µM Zol treatment in the bone-seeking clone and no reduction in MDA-MB-231.
The migration reduction rate was 88% in the bone-seeking clone and no reduction in MDA-MB-231.
There was a significant difference between the bone-seeking clone and MDA-MB-231 in the reduction rates of both cellular proliferation and migration. Although the effect of gefitinib was synergistic with that of Zol in the bone-seeking clone, it was not clear in MDA-MB-231.
Conclusion: There appear to be at least two independent signaling pathways that occur in osteolytic bone metastasis. One is involved in the bone resorption of bisphosphonates, and the other is an EGFR signaling pathway. Clinically, the combination of Zol and gefitinib is suggested to be a strong therapy specific to bone metastasis.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-13-09.