bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticancer prescription appropriateness: The APA score—A new method to assess anticancer prescriptions in the clinical setting.
Authors: Launay-Vacher V. , Aujoulat O. , Brandely M. , Chevrier R. , Dumas L. , Favier B. , Pelloquin A. , Rioufol C. , Rey J. 
Published: February 2017

261 Background: Innovation is crucial in cancer care and access to innovation cannot be—only—economically ruled. We need new drugs, more effective and/or better tolerated to improve the care of our patients. In this context, we need new tools to evaluate the appropriateness of anticancer drugs prescriptions. In fact, the better the appropriateness, the better is the patient care, and the overall balance, including economically. Methods: A group of 9 pharmacists from university hospitals, general hospitals, and cancer centres joined under the umbrella of the European Fellowship for Pharmacists (EFP) association. The aim was to set up a common process in evaluating the appropriateness of anticancer drugs prescriptions (ADP), focusing on innovative drugs, but not only. Results: The backbone of our work was to put back the patient at the centre and not to focus on the costs as themselves. We defined a composite criterium called “value of an ADP” which included the costs of course in addition to several factors such as the existence of alternatives for a particular patient, the level of evidence from literature data, the existence of other indications, and several other items. First, a decision tree was elaborated, which allows systematic and standardized screening of ADP leading to early identification of ADP which do not necessitate thorough evaluation: prescription within the terms of either a market authorisation or a Temporary Therapeutic Protocol, or a Temporary Utilization Authorization (ATU), and not on a clinical trial. For the other prescriptions, an evaluation grid coupled to a score was set up. This APA Score (Anticancer Prescription Appropriateness) will allow to decide whether or not a ADP, in a particular clinical context and patient, should be judged as appropriate or not. Conclusions: At the time of this abstract: the evaluation grid has been discussed, modified, and validated with the participation of two clinical oncologists, specialized in Breast Cancer; the APA scoring is currently under testing by a team of methodologists and bio-mathematicians; and the grid and the APA Score will be tested in “real-life” within the departments of the people involved in the group by the end of 2011.
MEDI-573 as a novel approach to IGF-1R and IR-A signaling inhibition by blocking IGF ligands: Phase I PK/PD, safety data, and disease linkage studies in breast cancer.
Authors: Haluska P. , Huang J. , Lam B. , Liang M. , Huang W. , LoRusso P. , Menefee M. E. , LaVallee T. , Yao Y. , Viner J. 
Published: February 2017

271 Background: MEDI-573 is a dual-targeting human antibody that neutralizes IGF-I/-II ligands and inhibits IGF-1R and insulin receptor-A (IR-A) signaling pathways, which play a role in breast and other epithelial cancers. By sparing IR-B and its hybrid receptors, MEDI-573 is expected to achieve antitumor activity without perturbing glucose homeostasis. Methods: In a 3 + 3 dose-escalation trial ( NCT00816361 ), patients with advanced solid tumors, KPS ≥ 60, received MEDI-573 as a weekly 1-hr IV infusion at 0.5, 1.5, 5, 10, or 15 mg/kg every 21 days. Objectives included determination of MTD, safety profile, pharmacokinetics (PK), pharmacodynamics, and tumor response. In a separate biomarker study, mRNA expression of IR-A and IR-B was compared in HR+/HER- breast cancers. Results: Patients included 13M/12F (17 evaluable for efficacy at data cutoff); median age 59 yrs (range 37-78). No DLTs, drug-related SAEs, or significant toxicity patterns were reported. Forty-five AEs were considered treatment-related (% of patients): decreased appetite (28%), fatigue (24%), nausea (20%), diarrhea (16%), and anemia (12%). Hyperglycemia occurred in 2 patients, 1 with evidence of prestudy insulin resistance. No other significant changes in plasma glucose levels occurred. MEDI-573 had dose-proportionality, with AUC of 415 ± 165, 597 ± 298, and 1940 ± 904 d*μg/mL at 5, 10, and 15 mg/kg, respectively. Suppression of free IGF-1 and -2 was fully achieved at doses ≥ 5 mg/kg. Stable disease spanning ≥ 12 wks (range 12-36+) was seen in 6/17 patients. No antidrug antibodies were reported. In a study to identify breast cancer subsets that are dependent on IGF signaling, the IR-A:IR-B ratio was significantly higher in HR+/HER2- breast cancer than matched adjacent normal tissues and in proliferative luminal B than in luminal A breast cancer. Conclusions: MEDI-573 showed acceptable safety and favorable PK profiles without significant changes in glucose levels. The IR-A:IR-B ratio supports a biomarker approach for MEDI-573 patient stratification. A biomarker-rich phase Ib/II study of MEDI-573 with an aromatase inhibitor in patients with advanced HR+/HER2- breast cancer opens in 2011.
Gemcitabine (G) and cisplatin (C) as first-line treatment of metastatic breast cancer (MBC): Results of phase II trial.
Authors: Karthaus M. , Poddubnaya I. , Churilova L. , Khasanov R. , Veremeychuk T. , Rumyantseva E. , Garin M. , Brichkova O. , Heinrich B. , Heinemann V. 
Published: February 2017

273 Background: G has been studied in combination with a variety of agents known to be active in cancer. G has a mild toxicity profile. GC is active in various advanced tumors. Splitting of C dose (D 1 + d8) is better tolerated and can be a good alternative to once a cycle in pts with advanced breast cancer. This phase II trial evaluates G (1000 mg/m2) C (35 mg/ m2) d1+8 repeated every 21 d in the 1st-line treatment of metastatic breast cancer (MBC). The primary objective of the study was to determine the objective tumor response rate (ORR) of 1st-line GC in patients with metastatic breast cancer.The one-stage design tested the null hypothesis that the true response rate for this population should be equal to 50% for efficacy. Overall survival (OS), time to progression (TTP) and toxicity were evaluated. Methods: 70 female MBC pts with the median age of 49.8 ys (range 29.6-80.0) were enrolled. Tumor assessment was performed every other cycle by standard criteria including CT or MRI. 67 pts received a total of 310 cycles GC, out of these 54 pts were evaluable for efficacy. Results: Complete and partial responses were observed in 7/54 (13.0%) and 19/54 (35.2%) evaluable pts, respectively with an overall response of 48.2%. Disease stabilization was noticed in 19/54 (35.2%) pts. Progression was observed in 5/54 (9.3%) pts. TTP was 33.9 weeks (95% CI, 23.9-48.0). OS was 84.0 weeks (95% CI, 58.6-119.3). 1-year overall survival rate was 68.4% (95% CI, 53.6-79.3%). Hematological toxicity G4 was neutropenia in 14.9% (10/67), and no G4 thrombocytopenia. Hypotension G4 (1.5%) was the only severe non-hematological toxicity. Conclusions: GC in the first-line treatment of MBC, demonstrated a substantial overall response rate and had a good toxicity profile. GC is a suitable option for first-line MBC in selected pts.
Comparison of MammaPrint, BluePrint, and TargetPrint with clinical parameters in patients with breast cancer: Findings from a prospective United States cohort.
Authors: Nguyen B. , Deck K. B. , Sinha R. , Kerlin D. , Barone J. , Rivera E. , Garcia A. , Yao K. , Stork-Sloots L. 
Published: February 2017

47 Background: MammaPrint (MP) is a powerful predictor of disease outcome in early stage breast cancer. In addition, TargetPrint (TP), a microarray-based test that measures the mRNA expression level of ER, PR and HER2 and an 80 gene expression Molecular Subtyping profile BluePrint (BP) were developed. In the present study, MP, BP and TP were measured in a prospective U.S. breast cancer patient cohort. Methods: MP results were evaluated in fresh tumor samples from 127 breast cancer patients (T1-4N0-2; median age 62 [39-97 yr]) collected by core needle biopsy or from a surgical specimen between July 2008 and January 2011. We compared treatment advice as recommended by NCCN guidelines and classification according to MP. In addition, we compared IHC/FISH ER, PR and HER2 assessments with TP. The MP and BP results were used to subtype the patients into molecular subgroups. Results: For the group of patients (n=59) for which NCCN recommends the use of a multi-gene signature for determining chemotherapy treatment recommendations, 42 patients were classified as High Risk and 17 as Low Risk by MP. Comparison of TP with IHC/FISH indicated a concordance of 98% for ER, 94% for PR, and 98% for HER2. For a subgroup of 53 patients combined MP and BP results were available; 18 patients were Luminal-type/MP Low Risk, 27 patients were Luminal-type/MP High risk, 1 patient was Her2-type/MP Low Risk, 1 patient was Her2-type/MP High Risk and 6 patients were Basal-type/MP High Risk. Conclusions: Adding the multi-gene signature MammaPrint, as well as BluePrint and TargetPrint provides additional information for treatment guidance. By combining MammaPrint with the BluePrint molecular subtyping profile, specific groups of patients can be recognized that are at high risk of recurrence and that would possibly benefit from specific treatment. This study shows that TargetPrint provides high quality second opinion for local IHC/FISH assessment.
Molecular profiling of metastatic breast cancer in body cavity fluids.
Authors: Ashfaq R. , Fong E. 
Published: February 2017

61 Background: The diagnosis of malignant effusion signifies disease progression and is associated with a worse prognosis regardless of tumor origin. The cancer cells in fluids have unique genotypic and phenotypic characteristics that are uniquely different from the primary tumor. Therapeutic guidance should be based on the evaluation of tumor cells in effusions. This study reports the feasibility of molecular profiling for breast cancer metastasis in pleural and peritoneal fluids. Methods: A computer search was conducted to retrospectively identify malignant fluid samples or cell blocks for molecular profiling. A cell-block was either prepared or available for testing for all samples. An H&E slide was prepared from the cell- block and reviewed by a pathologist before any testing. Malignant cell percentages were determined for purpose of DNA microarray analysis and Sequencing. Appropriate clusters and malignant cells were marked for FISH. The results were reviewed and data compiled to calculate the yield of various molecular predictive tests. Results: We studied 172 fluid of which 28 were metastatic breast cancer (16.2%). Of the 28 breast cases, 10 IHC biomarkers could be performed in 20 (71.4 %), 1-9 in 1 (3.5 %), while 7 (25%) were insufficient. DNA microarray analysis was done in 10 (35.7%), FISH for EGFR 7 (25%), Her2 Neu FISH 11(39%), cMYC FISH 5 (17.8%) and TOPO2a by FISH 3 (10.7%). Combined IHC/FISH/MA data was available in 10, IHC and FISH data in 11 and IHC and MA data in 10 cases. Combined results of predictive markers provided information on therapeutic guidance in 21 of 28 cases. Conclusion: Molecular profiling of malignant fluids offers additional opportunities for testing those patients where other tissue samples such as needle core biopsy or resection samples are not available. Molecular profiling provides insight into the molecular characteristics of malignant cells in body cavity fluids and associated expression of unique therapeutic targets.
Evaluation of the performance of breast cancer cell line–derived multigene predictors of chemotherapy response in multiple clinical trials.
Authors: Song N. , Rice S. D. , Gingrich D. , Wang D. , Tian C. , Ding Z. , Brower S. L. , Ervin P. , Gabrin M. J. , Shen K. 
Published: February 2017

64 Background: While various multi-gene predictors (MGPs) of chemotherapy response have been developed based on cancer patient primary tissues or cancer cell-lines, the accuracy and consistency of these predictors remain a concern in clinical validation studies. In this study we developed four unique MGPs for chemotherapy response from breast cancer cell lines and performed a systematic evaluation of the performance of these MGPs using data from five distinct clinical trials. Methods: Forty-six immortalized breast cancer cell-lines were exposed to various concentrations of drug combinations [paclitaxel, 5-fluorouracil, doxorubicin, cyclophosphamide (TFAC); 5-fluorouracil, doxorubicin, cyclophosphamide (FAC); 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and epirubicin, cyclophosphamide (EC)] using an in vitro chemosensitivity assay. Utilizing publicly available breast cancer cell-line microarray data, genes highly associated with in vitro chemosensitivity were selected as candidate MGPs. Five independent and publicly available clinical trials were used for validation. In three of these clinical trials patients were treated by TFAC, while EC, FAC or FEC were used in the other two trials. All five studies involved neoadjuvant chemotherapy treatment, and pathologic complete response (pCR) was used as the endpoint. The association of MGPs with pCR was assessed using receiver-operator curve (ROC) analysis and area under the ROC (AUC) was used to evaluate the performance of prediction. Results: In five independent clinical trials, the MGPs predicted patient pCR to EC, FAC/FEC and three TFAC treatments with an AUC of, 0.671, 0.632, 0.735, 0.738 and 0.647 respectively. Conclusions: In the five independent clinical trials in which patients were treated by various chemotherapy agents, the performance of MGPs is promising. These results demonstrate the feasibility of using breast cancer cell-line derived MGPs to predict breast cancer patients’ chemotherapy responses.
Diffusion-weighted magnetic resonance imaging in patients with known or suspected breast malignancy: Correlation between apparent diffusion coefficient and histopathologic diagnoses.
Authors: Kim A. C. , Ying D. , Sheth P. , Park J. M. 
Published: February 2017

65 Background: Magnetic resonance imaging (MRI) is an important imaging modality for evaluating patients at high risk for breast malignancy. However, the role and utility of diffusion-weighted imaging (DWI) in breast MRI has not been fully elucidated. This study was designed to investigate the relationship between apparent diffusion coefficient (ADC) values and histopathologic diagnoses in benign and malignant breast pathologies as well as to assess the relative diagnostic value of this parameter. Methods: We searched our database for patients who received breast MRI studies from February 2010 through March 2011. We then identified those patients who had either known or suspected breast malignancy and who had also undergone DWI. Breast abnormalities were identified through a review of the short tau inversion recovery (STIR) and T1-weighted pre- and post-contrast images. DWI images were evaluated and the corresponding ADC values were calculated. These lesions were correlated with histopathologic results when available. Results: A total of 174 patient MRI studies were evaluated. Single dominant lesions were assessed and included biopsy-proven infiltrating ductal carcinoma (IDC), biopsy-proven ductal carcinoma in situ (DCIS), and benign lesions including cysts. The median ADC value for IDC was 118 x 10-5 mm2 s-1. The median ADC value for DCIS was 123 x 10-5 mm2 s-1. Finally, the median ADC value for breast cysts was 217 x 10-5 mm2 s-1. Conclusions: As the role of MRI continues to evolve in the evaluation of breast pathology, the addition of DWI may increase diagnostic confidence for breast cancer, allowing for further differentiation from benign lesions. DWI is feasible to implement in many clinical practices and correlates with imaging features of breast cancer. The DWI images are acquired rapidly and without intravenous contrast. This method of imaging could be used in short intervals to assess treatment response to therapies such as biologic inhibitors or radiation therapy.
Evaluation of whole-body FDG-PET in breast cancer screening.
Authors: Nishizawa S. , Kodama H. , Okada H. 
Published: February 2017

66 Background: The utility of whole-body FDG-PET for the detection of breast cancers in a screening program is not well investigated. Methods: We analyzed data from a cancer screening program including whole-body FDG-PET performed for consecutive 2065 asymptomatic women (age: 40 to 80 y.o. with mean ± SD of 56.1 ± 8.6 y.o.) without a previous history of breast cancer. They underwent the initial screening between September 2003 and December 2008. The screening included neither mammography nor ultrasonography of the breast. Final results of cancers and/or follow-up data more than 1 year following the screening were available in 1822 of the 2065 (88.2%: 941 by the following screening and 881 by the response to questionnaires). Data of the second screening in 670 women (age: 55.0 ± 8.0 y.o.) of the 941, who didn’t have cancer at the initial screening and received the second screening by December 2008 and within 2 years of the initial screening were also analyzed. Final results and/or follow-up data more than 1 year were available in 642 of the 670 (95.8%: 573 by a subsequent screening and 69 by the response to questionnaires). Results: Data were analyzed as of the end of 2010. In 2 years after the initial screening, 57 cancers of a variety of organs including 12 of the breast were confirmed. Nine (stage 0: 1, I: 7 and IIA: 1) of the 12 were proven in 29 women with PET positive results and 3 (stage I: 1, IIA: 1 and not available: 1) in 2036 women with PET negative results. In 2 years after the second screening, 9 cancers including 4 of the breast were confirmed. Three of the 4 (stage 0: 1, I: 1 and IIB: 1) were diagnosed in 9 women with PET positive results and 1 (stage I) in 661 with PET negative results. Two of the 4 PET negative cancers were diagnosed after developing symptoms and the remaining 2 were detected by another screening. Sensitivity, specificity, positive and negative predictive values and false positive rate of the initial screening were 75.0% (9/12), 99.0% (2033/2053), 31.0% (9/29), 99.9% (2033/2036) and 1.0% (20/2053), respectively. Conclusions: Whole-body FDG-PET had the capability to screen the breast with a very low false positive rate and high positive and negative predictive values, and could detect breast cancers of asymptomatic women at early stages with reasonable sensitivity.
MRI versus breast-specific gamma imaging (BSGI) in the detection of synchronous breast cancer: A prospective head-to-head trial.
Authors: Kirstein L. J. , Keto J. L. , Sanchez D. P. , Fulop T. , Cohen I. , Cohen J. M. , Harshan M. , Boolbol S. K. 
Published: February 2017

72 Background: Literature suggests that MRI identifies additional mammographically and sonographically occult cancers in 8-10% of newly diagnosed breast cancer patients. We have reported comparable sensitivity of BSGI to MRI in the detection of the known index cancer. We sought to prospectively compare BSGI to MRI in the identification of additional occult malignancies in newly diagnosed breast cancer patients. Methods: Patients with newly diagnosed breast cancer from June 1, 2009 through February 4, 2011 were consented for an IRB approved protocol in which they underwent both breast MRI and BSGI. Each imaging study was read by a dedicated breast radiologist, with one reading all MRI, and another reading all BSGI studies. All subsequent biopsies were performed percutaneously under image guidance and reviewed by dedicated pathologists. The identification of additional occult breast cancers by MRI and BSGI was compared. Results: Eighty-five patients underwent both MRI and BSGI. Twenty-one patients elected to undergo mastectomy without further management of imaging findings and were excluded, leaving 64 eligible patients. No additional lesions were found in 22 patients. Twenty-one patients had benign pathology on biopsied imaging findings. Metastatic axillary lymph nodes, satellite lesions or larger extent of disease was identified in 11 patients. Eleven occult breast cancers were identified in 10 patients (15.6%), 6 on MRI alone (9.4%), 3 on BSGI alone (4.7%), and 2 by both modalities (3.1%). There was no significant difference in the identification of occult cancer between MRI and BSGI (chi-square 0.77, p>0.1; Table). Conclusions: BSGI has previously been shown to be as sensitive as MRI for detecting known invasive and in situ breast carcinoma. This study shows that BSGI is equally sensitive to MRI in the detection of synchronous mammographically and sonographically occult cancers in newly diagnosed breast cancer patients. Further research is needed to identify the false positive rates of BSGI and the effect on surgical management in comparison to MRI. [Table: see text]
Stage IV breast cancer in the community hospital setting: Primary tumor extirpation effect on overall survival.
Authors: Tjoe J. A. , Robinson L. A. , Stephenson J. , Marx J. J. 
Published: February 2017

90 Background: Publications from academic centers and national cancer databases suggest a survival advantage for women who undergo primary tumor extirpation in the setting of known distant disease. We asked if similar findings exist in a community hospital setting. Methods: 15,887 patients entered in a longitudinally maintained breast cancer database (encompassing a system network of 13 community hospitals) during 1985-2009 were analyzed for those diagnosed with stage IV disease upon initial presentation. The cohort was divided into those who underwent primary tumor resection, and those who did not. The two subgroups were compared for patient demographics, tumor characteristics, sites of distant metastases, systemic treatment, and overall survival (OS). Results: 643 (4.05%) presented with an intact primary breast malignancy and synchronous distant metastasis. Median age at diagnosis: 66 years (range 22-96). Median OS: 15 months (range 0-249). 264 (41.1%) patients underwent primary tumor resection as part of first course treatment. On Kaplan-Meier univariate analysis, patients who underwent surgical extirpation of the primary tumor demonstrated improved median OS compared to those who did not (26 vs 10 months; p<0.0001, HR 0.52). Age at diagnosis <50 (p=0.0003, HR 0.65) and oligometastasis to bone (p=0.0002, HR 0.72) were statistically significant predictors of improved OS. Race, primary tumor size, and ER status alone did not influence OS. Those ER+ patients who underwent primary tumor excision in addition to chemotherapy and/or hormonal therapy fared significantly better than those treated with systemic therapy alone (32 vs 17 months; p<0.0001). Chemotherapy 16+ weeks prior to surgery improved OS compared to those who had surgery <16 weeks after starting chemotherapy. While there was no difference with regards to type of resection (partial vs simple vs modified radical mastectomy), clear margins were imperative to optimize OS. Conclusions: Patients with stage IV breast cancer treated at community hospitals also demonstrate improved OS after primary tumor extirpation, especially in the context of a multimodality approach combining chemotherapy and/or hormonal therapy preceding surgery.