bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving patient safety by minimizing chemotherapy dosing errors.
Authors: McCrone Daniel , Tran Cecilia , Stone Nelly 
Published: February 2017

99 Background: Medication dosing errors in adult outpatient settings continues to be a significant source of morbidity. One recent study reported that approximately 7% of adult patients receiving chemotherapy experience medication errors (Kathleen E. Walsh, et al. Medication Errors Among Adults and Children with Cancer in the Outpatient Setting, Journal of Clinical Oncology, 2009). In 2011, New Century Health implemented a quality improvement project focused on minimizing chemotherapy medication errors. This study describes the oncology quality management program used with the Midwestern oncology providers of a large health plan. Methods: An analysis determined the overall medication dosing error rate and the number of oncologist-to-oncologist interventions. In addition, the root cause of each medication error was identified. Results: During the course of the year, 2,395 chemotherapy treatment plans were reviewed for compendia alignment. In 235 cases, the plans did not align with compendia, were identified for peer-to-peer consultation and were voluntarily withdrawn by the prescriber. Evidence-based plans were subsequently resubmitted for approval. Of the original treatment plans, 68 contained dosing errors. The most common dosing errors included: frequency (60.3%); sub-therapeutic (13.1%); super-therapeutic (14.7%); and loading dose for continuation (10.3%). The full year 2011 medication error rate was 2.8%. Conclusions: The integration of clinical decision support tools for dosing verification with oncologist-to-oncologist clinical review improved patient safety by identifying serious errors prior to treatment. These findings underscore the issue that many chemotherapy medication errors are preventable and arguably the medication error rate should be zero. [Table: see text]
Quantitative gene expression by RT-PCR in classic and variant lobular carcinoma in ER+ breast cancer.
Authors: Anderson Joseph Michael , Yoshizawa Carl N. , Watson Drew , Tan Vivian , Bailey Helen , Tsiatis Athanasios C. , Shak Steven , Baehner Frederick L. 
Published: February 2017

11 Background: Classic lobular carcinoma is characterized by a distinctive morphology, loss of E-cadherin commonly due to mutation or deletion of CDH1 on chromosome 16q, and a variable clinical course. Variants (pleomorphic, solid and alveolar) with distinct morphologies and potential differences in outcome have been described (Rosen 2009). Herein we provide an 8-year update of the patterns of quantitative gene expression as measured by the 21 gene Oncotype DX assay observed between ductal NOS (DC) and classic and variant lobular carcinomas. Methods: All tumors analyzed in the Genomic Health laboratory from 6/1/04-5/31/12 were included. Central path used WHO criteria for classification of classic lobular (CL), solid and alveolar lobular (SAL), and pleomorphic lobular (PL) carcinomas. Quantitative expression of 16 cancer related genes was measured on a scale from 2 to 15 (relative to reference genes) where a 1 unit increment is associated with an ~2-fold change in expression. Descriptive statistics for RS & individual genes [ER, PR, invasion gene group (IGG) and proliferation gene group (PGG)] among the subtypes were obtained. Comparisons of means among the subtypes were adjusted to control the overall error rate under any complete or partial null hypothesis. Results: DC accounted for 81.8% of 286,726 cases, CL 7.3%, SAL 0.4% and PL 0.4%. For all types a continuous range of RS was observed. DC had the greatest percentage of high risk RS followed by SAL, PL and CL. DC had the highest mean RS and PL and CL had the lowest RS. SAL had the highest mean ER expression and CL and PL had the lowest ER expression. These results may reflect a submission bias and are not population based. The proportion with ER+/PR- phenotype was slightly different among the subtypes: SAL (24.0%) and PL (19.4%) had a higher incidence compared to DC (14.1%) and CL (15.2%). SAL had the highest PGG expression; CL had the lowest. DC had the highest IGG; CL had the lowest. Conclusions: CL and the lobular carcinoma variants are characterized by differential patterns of gene expression. Outlier cases are not infrequent within each of the special subtypes in this large observational cohort. The variation in gene expression, noted by histologic subtype, will be presented in detail.
Age disparity in Oncotype DX testing in a community oncology setting.
Authors: Khajuria Suheir , Adams Ashley , Schreiber Andrew Michael 
Published: February 2017

119 Background: Oncotype Dx is a twenty-one gene prognostic assay traditionally used to predict response to systemic chemotherapy in early stage, hormone positive, node negative, HER2neu negative breast cancer. We evaluated the prevalence of Oncotype Dx testing in a local community oncology setting, co-relation with patient age and co-relation of recurrence score with receiving chemotherapy. Methods: A retrospective chart review was performed on all 406 breast cancer patients who presented to our local cancer center between January 2011 and March 2012. Pathology (ER/PR/HER2neu), eligibility for Oncotype Dx testing, patient characteristics and use of chemotherapy were analyzed. Results: Based on National Comprehensive Cancer Network guidelines, 147/406 met standard criteria for Oncotype Dx testing. Of these, 64 patients (43.8%) received testing, and 6 (4.1%) received Mammaprint testing. Oncotype Dx testing was ordered on 53.5% (54/101) of patients younger than 70 years of age and 22.2% (10/45) of patients 70 years of age or older. Increasing age was significantly related to decreased Oncotype Dx testing (p = 0.0021). Mean age of patients who did and did not undergo testing was 59.8 ± 9.9 and 66.2 ± 12, respectively. Patient age was not significantly related to the decision to undergo chemotherapy (p = 0.1085). Oncotype Dx recurrence score was a significant predictor of choosing chemotherapy when appropriate at the cancer center (p=0.0091). Conclusions: The likelihood of receiving Oncotype Dx testing decreased with the patient’s age. However, the decision to undergo chemotherapy was not related to age. Factors such as patient's aversion to chemotherapy or decision to consider chemotherapy regardless of recurrence score may have influenced the ordering of Oncotype Dx testing. Further studies are warranted to evaluate physician, patient and other barriers to Oncotype Dx testing.
Weight change in patients with treatment of breast cancer.
Authors: Chaudhary Lubna , Wen Sijin , Xiao Jie , Swisher Anne , Kurian Sobha , Abraham Jame 
Published: February 2017

127 Background: Studies have shown that breast cancer (BC) treatment can increase weight (wt). Wt gain during chemotherapy is usually significant and maybe associated with poor survival. Role of current treatment regimens and wt gain is not reviewed. Methods: We retrospectively analyzed the mean percentage (%) wt change during the 1st year following BC diagnosis in 246 patients (pts) between Sept 2007 and Oct 2010. Kruskal-Wallis test and post-hoc pairwise comparisons were used to assess the influence of various factors including age, histology, stage, ER/PR/HER-2/neu status, menopausal status and types of therapeutic modalities received on the % wt change. Kaplan-Meier method with log-rank test was used to evaluate recurrence free survival (RFS). Local or distant recurrence and disease progression were events for RFS analysis and disease-free pts were censored at last follow-up. Results: Mean wt gain was 0.39% (±0.40) at 1 year from diagnosis of BC. Premenopausal status was the only factor associated with significant wt gain (+1.67% vs. -0.10% for postmenopausal pts; p=0.02). Stage ≥ III was associated with significant wt loss (-1.64% for III/IV vs. +0.85% for 0/I/II; p=0.02) and a lower RFS at 3yrs and 5yrs (p< 0.0001). Higher baseline wt (>90th percentile) did not have any significant impact on RFS at 3 years (0.84 vs. 0.91; p=0.19). There was no significant change in wt relative to other factors as shown in Table. Conclusions: Our study using current treatment regimens did not show any significant change in % wt with chemotherapy during the 1st year of BC diagnosis. Premenopausal status was the only factor associated with significant wt gain while stage ≥ III was associated with significant wt loss and lower RFS. [Table: see text]
Physical activity and fitness in women with metastatic breast cancer.
Authors: Yee Jasmine , Davis Glen M , Beith Jane McNeil , Wilcken Nicholas , Hui Rina , Harrison Michelle L. , Currow David , Emery Jon , Phillips Jane , Martin Andrew , Segelov Eva , Kilbreath Sharon Lynn 
Published: February 2017

136 Background: Women with metastatic breast cancer may survive for many years after disease onset, and there is little published evidence on their habitual levels of physical activity. The aim of this study was to investigate differences in physical activity levels and physical fitness between women with and without metastatic breast cancer. Methods: Seventy-one women with metastatic breast cancer (METS) aged 57.7 ± 9.5 y and 2.9 ± 3.1 y after disease onset, and 71 healthy controls (CONTROLS) aged 55.0 ± 9.4 y participated. Of those with metastatic disease, 27% had metastases in bone only, 35% in viscera only and 38% in both bone and viscera. Strength was measured using hand and leg dynamometry, aerobic fitness using the Modified Canadian Aerobic Fitness Test, and fatigue with the FACT-Fatigue questionnaire. Participants wore a SenseWear physical activity armband over 6 days, and the average steps taken per day over 5 of these days, where there was a minimum wear time of 8 hours per day, was derived. Results: METS possessed lower aerobic fitness than CONTROLS (25.3 ± 5.4 versus 31.9 ± 6.1 ml·kg·min-1 respectively; p<0.01). METS were significantly weaker than CONTROLS. Lower limb strength for the METS and CONTROLS was 53.8 ± 23.7 versus 76.0 ± 27.4 kg and handgrip strength was 26.6 ± 6.0 versus 30.2 ± 6.4 kg. METS were also significantly less active, attaining only 57% of the daily step counts of CONTROLS. Fatigue was significantly higher in women with metastatic cancer compared to their healthy counterparts (38.0 ± 9.8 versus 46.3 ± 4.6; p<0.01). Correlation between fatigue with average steps per day (r=0.46), handgrip strength (r=0.29) and leg strength (r=0.26) was low in the METS group. Conclusions: Women living in the community with metastatic breast cancer are weaker, have lower aerobic fitness, and are relatively inactive compared to their healthy counterparts. Increased fatigue in these women is poorly associated with their decreased physical activity levels, hand and lower limb strength. Women with metastatic breast cancer may benefit from a program directed at improving their strength and fitness. Acknowledgements: Funded by National Breast Cancer Foundation, Australia.
Utility of 2D-speckle tracking echocardiography in diagnosis of left ventricular dysfunction in anti-ErbB2 therapy.
Authors: Maurea Nicola , Piscopo Giovanna , Cipresso Clemente , Rea Domenica , Esposito Emanuela , Capasso Immacolata , Tocchetti Carlo G. , Arra Claudio , Coppola Carmela 
Published: February 2017

169 Background: ErbB2 is overexpressed in about 25% of breast cancers; in the heart, it modulates myocardial development and function. Trastuzumab (T), an anti-ErbB2 inhibitor, has improved the prognosis of patients with breast cancer, but is related to an increased risk of asymptomatic left ventricular (LV) dysfunction (3-34%) and heart failure (2-4%). Conventional measures of ventricular function, such as fractional shortening (FS) and ejection fraction (FE) are insensitive in detecting early cardiomyopathy induced by antineoplastic therapy. Here, we aim at assessing whether myocardial strain by 2D-speckle tracking (ST) is able to identify early LV dysfunction in mice treated with doxorubicin (D) and T, alone or in combination (D+T) and to relate data of cardiac function with tissue alterations. Methods: Cardiac function was measured with FS, by M-mode echocardiography, and with radial myocardial strain with ST in sedated C57BL/6 mice (8-10 wk old) at time 0, 2 and 6 days of daily administration of D (2.17 mg/kg/day), T (2.25 mg/kg/day), D+T (2.17 mg/kg/day + 2.25 mg/kg/day) and in a control group. In excised hearts, we evaluated TNFα and CD68 by immunohistochemistry; interstizial fibrosis was analyzed with picrosirius red staining. Results: FS was reduced in group D and D+T at 2 days (52+0.2% and 49+2%), both p<0.001 vs 60+0.4% (sham), while in group T it decreased only at 6 days (49+1.5% vs 60+0.5%, p=.002). In contrast, after 2 days, myocardial strain was already reduced not only in D and D+T, but also in T alone: 43+3%, 49+1%, and 44+7%, respectively, all p<0.05 vs sham (66+0.6%). Cardiotoxicity was associated with significant alterations in extracellular matrix remodeling as confirmed by an increase of interstizial collagen with D (4.56%), T (2.17%) and D+T (3.77%)at 6 days p<0.05 vs sham (1.17%) and by increased cardiac inflammation in fact the myocytes were positive for TNFα and CD68 cells/mm2at 6 days in group D (16.46% and 155), in group T+D (12.35% and 74.16) and in group T (5.65% and 72.32) p<0.01 vs sham (0.56% and 2.3). Conclusions: Myocardial strain identifies LV systolic dysfunction earlier than conventional echocardiography and can be a useful tool to predict cardiotoxicity in this setting.
Effect of eribulin on cell growth and PI3K pathway activity with and without RAD001 in triple-negative and HER2-expressing breast cancer.
Authors: Luyimbazi David , Luu Thehang H. , Xing Quanhua , Yan Jin , Tully Dylan , Han Ernest Soyoung , Yip Richard , Yim John H. 
Published: February 2017

173 Background: Patients with triple-negative breast cancer have high levels of Akt expression and activation of the PI3K-mTOR pathway. Eribulin is a microtubule-targeting agent with benefits in treating refractory triple negative disease. Our objective was to evaluate its efficacy in inhibiting PI3K pathway activity and cell growth both alone and in combination with the mTOR inhibitor RAD001. Methods: MDA468, BT549 and SKBR3 breast cancer cell lines were used for this study. MTT assays were used to assess growth inhibition after 72 hour treatment with eribulin alone and in combination with RAD001. Combination indices (CI) generated by Chou-Talalay plots were used to quantify synergy. Western blots were used to evaluate the expression of phosphorylated Akt-Ser473 (pAkt) and S6K1 after 24 hours of treatment with both agents. Results: Both MDA468 and SKBR3 cells treated with eribulin in varying concentrations showed inhibition of pAkt expression. Standard dilutions of eribulin in combination with log dilutions of RAD001 resulted in marked synergistic growth inhibition (CI<<1) in both MDA468 and BT549 cells. Western blot analysis for MDA468 cells treated with the combination erubulin and RAD001 showed a dose related suppression of pAkt along with complete inhibition of pS6K1, while RAD001 alone increased pAkt. Conclusions: Our study shows dose related inhibition of Akt activation as well as inhibition of cell growth in triple negative breast cancer and HER2 cell lines treated with eribulin alone or combined with RAD001. We also show reversal of the pAkt feedback response seen with mTOR inactivation, and a significant synergistic growth inhibition with combination treatment. These findings point to a potential role for eribulin and RAD001 in the treatment of refractory triple-negative breast cancer. [Table: see text]
Real-world analysis of eribulin in metastatic breast cancer (MBC): An assessment of time to treatment failure (TTF) in a community oncology setting.
Authors: Dranitsaris George , Tripathy Debu , Beegle Nancy L. , Kalberer Traci L. , Cox John David , Faria Claudio 
Published: February 2017

174 Background: There have been important advances in the treatment of patients with MBC. However, certain patient subgroups such as whose who are triple negative remain a therapeutic challenge. Eribulin is the newest cytotoxic to gain regulatory approval for MBC in the Unites States. In this analysis, the safety and efficacy of eribulin in TNBC patients and those with prior anthracycline exposure were assessed in an early cohort treated in a U.S. community oncology setting. Methods: Ninety patients treated in eight community oncology clinics across the U.S. were identified. Patients were followed from the first cycle of eribulin until disease progression, discontinuation due to toxicity, or death. Data collection included baseline patient and disease characteristics, prior and subsequent anticancer therapy, use of supportive care drugs, number and type of dose limiting toxicity, delivered dose intensity, duration of eribulin therapy and time to treatment failure (TTF). Results: Eribulin was administered after a median of three prior lines of chemotherapy (range 0 to 15). The drug was delivered as a single agent in 79 of 90 patients (88%) at the clinically approved dosage of 1.4 mg/m2on days 1 and 8 of a 21 day cycle. Patients received a median of 4 cycles (1 to 16) for an overall mean duration of 2.9 months (0 to 14.2 months). Approximately 17 of 90 patients (18.9%) were identified as triple negative and 57 of 90 (63.3%) had received prior anthracycline treatment. The median TTF (inter quartile range) was 4 mon (2.3 to 5.6) in all patients. There were no significant differences in TTF by triple negative status (HR=0.1.22, p = 0.49) and prior exposure to anthracyclines (HR=0.78, p = 0.15). In all patients, the most common dose limiting toxicities were neutropenia (32%), anemia (31%), neuropathy (21%) and febrile neutropenia (8.9%). These events led to the premature discontinuation of eribulin in 8 of 90 patients (8.9%). Conclusions: TTF with eribulin was comparable regardless of triple negative status and prior exposure to anthracyclines. These findings are consistent with results from previous clinical studies and warrant further real-world analyses in a larger population.
MRI screening of women at average risk of breast cancer.
Authors: Schrading Simone , Kuhl Christiane K. 
Published: February 2017

21 Background: In asymptomatic women at average risk, mammography alone, possibly amended by the US, is recommended for screening. MRI is established for screening women at high risk, but there are no data available to support its use in women at average risk. Methods: Between Jan 2005 and Dec 2012, 1,387 women at average risk, i.e. without personal or family history of breast or ovarian cancer or tissue diagnosis of atypias underwent 1,705 annual MRI screening studies. Mean/median age was 55/56, range 40-79. All women had normal CBE and normal double-read 2-view digital screening mammograms. In women with breast densities, additional US had been performed and women were included if also US was normal. Patients underwent bilateral DCE MRI at 1.5T using a 2D GE pulse sequence. Results: A total of 54 MRIs were rated positive (MR-BI-RADS 4/5) (54/1705; 3.2%). Biopsies performed in these women were positive for breast cancer or DCIS in 18, and revealed high risk lesions in 8 patients, yielding an additional cancer yield of 11/1,000. In 28 women, biopsy revealed benign changes only. This translates into a PPV of 33% (18/54), or 48% (26/54) if high risk lesions are included. Of the 18 cancers, 11 (61%) were invasive and 7 (39%) DCIS. Mean size of invasive cancers was 11 mm (median 10, range 4 -22). Invasive cancers were intermediate or high grade in 9/11, DCIS in 6/7. All invasive cancers were staged pN0, M0. Minimal cancer rate was 13/18 (72%). Distribution of mammographic breast densities in women with MRI-diagnosed cancer was as follows: ACR I in 2 (11%), ACR II in 3 (17%), ACR III in 8 (44%), ACR IV in 5 (28%). This was equivalent to the distribution of breast densities in the entire cohort. Conclusions: In this cohort of heavily pre-screened women at average risk, the additional cancer yield achieved through MRI was high (11/1,000). Although the biologic profile of MRI-only detected additional cancers was indicative of prognostically relevant disease, with a high proportion of high-grade cancers, stage distribution of cancers was favorable. Mammographic breast density did not predict the likelihood with which additional cancers were identified through MRI. In women with dense breasts who underwent screening US in addition to mammography, there is still a significant reservoir of undetected cancers.
Breast cancer stem cells mutations: A new understanding of intratumoral heterogeneity.
Authors: Donovan Cory , Skinner Amy , Pommier Rodney F. , Alabran Jennifer L. , Muller Patrick , Gordon Nicole , Vetto John T. , Naik Arpana , Pommier SuEllen 
Published: February 2017

25 Background: Breast cancer has long been recognized as a heterogeneous disease. This has profound implications for diagnosis, treatment and disease recurrence. Oncogenic mutations have been identified in breast cancer cells with stem-like and progenitor properties (BCSC). We have previously reported that BCSC mutations correlated with axillary lymph node metastases. This was even more significant when micrometastatic disease was included. Our hypothesis is that tumor heterogeneity extends to the genetics of BCSC, and that BCSC mutations are better predictors of lymph node status than whole tumor genetics. Methods: BCSC from fresh tissue specimens were matched to their whole tumor specimens. BCSC and whole tumor DNA were sent for PCR-based mutation analysis. Patient data was collected by chart review. Results: Twenty-eight matched BCSC and whole tumor samples were analyzed. PI3K/Akt signaling mutations in PIK3CA, AKT1, HRAS, and MET were identified in BCSC from 10 tumors. In 4 of these, mutations were also identified in the corresponding whole tumor specimens. In 4 patients, mutations were identified in whole tumor samples only. Fourteen tumors had no mutations. Tumor stage, grade, receptor status, and age did not correlate with tumor or BCSC mutation status. In contrast to BCSC mutations, mutation status of the whole tumor did not correlate with micro or macro metastatic disease in the lymph node (p = 0.92). Conclusions: Mutations in BCSC are more predictive of lymph node metastases than mutations identified in the tumors. Thus, PI3K/Akt pathway mutations in tumor precursor cells may have a stronger influence on tumor metastatic potential than mutations identified in whole tumor samples. Whole tumors and BCSC populations demonstrate significant heterogeneity, as mutations identified in BCSC and tumors were not always concordant. Rare BCSC populations must be tested separately as they provide crucial prognostic and treatment information in conjunction with whole tumor genetic analyses.