bluuebunny/crossref_metadata_2025 huggingface dataset:
Kaizen quality initiative to improve patient satisfaction and throughput in an academic cancer center.
Authors: Dougherty David , Murray Patti , Berkhof Julie Ann , Levandowski Lynn , Khorana Alok A.
Published: February 2017

78

Background: Lean management principles have long been employed in manufacturing to improve operational efficiency but have only recently been adopted into healthcare settings. To address prolonged wait times and inadequate performance on patient satisfaction surveys, our cancer center utilized a Kaizen event as part of a quality improvement initiative. Methods: We utilized methods of Kaizen philosophy to evaluate all processes related to the patient experience in the outpatient facilities of the James P. Wilmot Cancer Center of the University of Rochester. The Kaizen initiative was conducted by a multidisciplinary group and consisted of an intensive 5-day induction period to identify problems within the system of care followed by regular quality improvement meetings. The group developed immediate solutions to some problems and identified priorities for the longer term. Changes in patient throughput times (time from clinic check-in to check-out) and patient satisfaction (utilizing Press-Ganey surveys) were tracked before and after initiating Kaizen and this report evaluates results over the first 12-month period. Results: Our Kaizen initiative involved a group of 17 faculty and staff who assembled during the induction period and met bi-monthly over the 12-month period from May 2011 to June 2012. Prior to the Kaizen intervention, mean throughput time for a 30-minute clinic visit was 80.34 minutes (n = 259; median 76; range 18 to 261) and mean overall patient satisfaction score for the quarter preceding the Kaizen was 89.3 (43rd percentile AHA Region 2). Over the 12 months following the Kaizen, mean throughput time reduced to 57.85 minutes (n = 249; median 53; range 11 to 205) and patient satisfaction scores improved to 91.9 (p<0.05; 63rdpercentile). Conclusions: Utilizing continuous process evaluation and Kaizen methodology, we reduced patient throughput times by 28% and improved patient satisfaction percentile rank by 20%. Ongoing efforts focus on utilizing continuous quality improvement to improve patient and family-centered cancer care. Kaizen is an effective, resource-neutral method for improving operational efficiency and patient-centered outcomes in an academic oncology practice.
Follow-up of long-term young breast cancer survivors.
Authors: Daly Corinne , Del Giudice Elisabeth M. , Sutradhar Rinku , Paszat Lawrence Frank , Wilton Drew , Rabeneck Linda , Baxter Nancy N.
Published: February 2017

8

Background: Evidence suggests breast cancer patients can be offered follow-up by family physician without concern of important recurrence–related serious clinical events occurring more frequently or quality of life being negatively affected. This study describes population-based patterns of follow-up care in 5-year recurrence-free young breast cancer survivors to determine factors influencing continued oncology follow-up in Ontario, Canada. Methods: We conducted a retrospective population-based cohort study using cancer registry and administrative data. Women diagnosed with an incident breast cancer aged 20-44 between 1992 and 1999, survived for at least 5 years and recurrence-free for 5 years past diagnosis were identified in the Ontario Cancer Registry. Each survivor was matched to 5 control women with the same calendar year of birth and place of residence in Ontario. We determined outpatient physician visits with primary care, medical, radiation and surgical oncology physicians to investigate trends associated with increasing survivorship and compared visit rates to controls. We used negative binomial regression to investigate factors predicting high utilization of oncology services among survivors after 5-year recurrence survival. Results: We identified 4,581 survivors and 22,898 controls. By year 10, 51% breast cancer survivors were still being followed by an oncologist. In the survivors, fewer physician visits were observed among recurrence-free breast cancer survivors as time increased from diagnosis (Visit Rate Ratio [VRR] =0.95, 95% CI: 0.94, 0.96). Breast cancer survivors diagnosed from 1992-1995 had a higher rate of physician visits than those diagnosed from 1996-1999 (VRR = 1.16, 95% CI: 1.07, 1.25). More oncologist visits were associated with patients visiting a female oncologist (VRR = 1.20, 95% CI: 1.09, 1.33) and fewer visits were associated with patients visiting an oncologist who practiced outside of a regional cancer center (VRR = 0.67, 95% CI: 0.58, 0.77). Conclusions: Oncology visits of young breast cancer survivors after 5-year survival were associated with oncologist factors indicating that prolonged oncology follow-up in breast cancer survivors may be driven by practice patterns rather than patients’ needs.
Minimizing wait time between chemotherapy and radiotherapy treatments.
Authors: Sauerbaum James J. , DeMaio Gina , Geiger Bradley , Cunningham Regina , Holmes Marianna , Avellino Amy , Cohen Roger B. , Metz James M. , Evans Tracey L.
Published: February 2017

82

Background: Members of the scheduling teams at the Abramson Cancer Center observed prolonged delays between chemotherapy and radiation therapy treatments scheduled by staff from 2 independent departments leading to inconvenience for patients receiving concurrent chemo- and radiation therapy (CRpts). Methods: An analysis of baseline data over 6 weeks revealed that for 157 unique consecutive patients undergoing daily chemotherapy and radiation (a total of 353 encounters), the mean time between scheduled treatments was 122 minutes. For 39% of encounters the wait time was greater than 120 minutes. To improve the adjacency of chemotherapy and radiation appointments and to consistently reduce wait time between treatments to less than 120 minutes, we formed a Chemotherapy/Radiation Scheduling Task Force consisting of patient service representatives, practice managers, and physician and nurse advisors. We determined that CRpts should be scheduled using a “huddle” strategy whereby prospectively identified CRpts are simultaneously scheduled for both treatments in a coordinated manner. Identifying CRpts for coordinated scheduling was facilitated by the creation of a chemo-radiation scheduling inbox to which clinicians and support staff e-mail names of new CRpts in order to alert the scheduling team. Our two lead schedulers meet 2-3 times per week to coordinate patient schedules. A weekly scorecard of the wait times for CRpts patients is distributed via e-mail to the clinicians and support staff. Results: Over the past 6 months, we have used the huddle method for 80% of 986 consecutive CRpt encounters. Our average wait time for huddle-scheduled encounters has been reduced to 62.5 minutes with only 9% of encounters having wait times over 120 minutes. For non-huddle-scheduled encounters, the average wait time is 129 minutes with 57% having wait times over 120 minutes. Conclusions: Utilization of a huddle scheduling method has successfully reduced wait time for CRpts. Use of the huddle method continues to grow with staff training and awareness of the new process.
Enabling quality improvement in systemic cancer treatment through a collaborative approach.
Authors: Simanovski Vicky , Hertz Sherrie , Green Esther , Meertens Elaine , Kaizer Leonard , Krzyzanowska Monika K. , Burns Judy , Woltman Kelly
Published: February 2017

88

Background: The Regional Systemic Treatment Program at Cancer Care Ontario (CCO) aims to ensure the highest quality of systemic treatment is available to Ontarians, as close to home as possible. CCO initiated a provincial collaborative with the aim of improving the safe delivery of parenteral chemotherapy from orders through preparation, to administration, for patients, and providers. Methods: From April 2011 to March 2012, interdisciplinary hospital teams across Ontario followed multiple Plan, Do, Study, Act cycles to perform QI projects focusing on safe delivery of systemic treatment. Over this period, three in-person sessions educating participants on improvement methodology were held. Monthly teleconferences and an electronic discussion forum encouraged a culture of knowledge sharing and collaboration. Results: 113 participants from 26 teams participated in a total of 81 improvement initiatives. 96% of participants surveyed indicated that the collaborative provided a valuable opportunity to network with peers, share ideas, and discuss lessons learned. During the collaborative, teams reported their progress on a scale of 1-5. At May 2011, teams averaged a self-assessment score of 1, indicating no progress had been made. By February 2012, this increased to an average score of 4, indicating significant progress and achievement of at least one improvement objective/goal. CCO has leveraged the foundations built by the collaborative to develop a Regional Quality and Safety Network. This network provides a regular forum for health care providers and administrators to share knowledge and collaborate on strategies for improving quality and safety in the delivery of systemic treatment. Conclusions: The collaborative demonstrated that the use of a formal quality improvement model is a successful mechanism for regional engagement; that provides the foundation necessary for building a provincial network with common goals and understanding regarding quality improvement. By educating participants, supporting local efforts and enabling knowledge transfer and exchange, the collaborative showed that shared ideas and even small changes can lead to large-scale improvements for patients and providers.
Understanding and improving chemotherapy ordering and delivery using process elicitation and validation.
Authors: Mertens Wilson C. , Christov Stefan C. , Cassells Lucinda Jane , Avrunin George S. , Clarke Lori A. , Osterweil Leon J. , Marquard Jenna L.
Published: February 2017

89

Background: Chemotherapy order/administration consists of complex, interrelated processes where errors have potentially severe consequences. We report a study that quantitatively and qualitatively evaluated chemotherapy delivery employing a formal process definition language to elicit and describe rigorously the process, then applied mathematical validation techniques to confirm the description, analogously to how computer software development and other industries use accurate, precise process definitions to assure soundness through redundancy and correct event sequencing. Methods: The process, including exceptional situations and individuals’ recognition of and responses to these, was elicited through informal, unstructured interviews with members of an interdisciplinary team. The resulting process description (or process definition), written in a notation developed for software development process assessment, guided chemotherapy process validation consisting of rigorous process definition analysis, direct observations, and semi-structured interviews to confirm the elicited details for the treatment plan sub-process. Results: The overall process definition yielded 467 steps; 207 steps (44%) were dedicated to handling 59 exceptional situations. Validation yielded 82 unique process events (35 new expected but not yet described steps, 16 new exceptional situations, and 31 new steps in response to exceptional situations). Process participants actively altered the process as ambiguities and conflicts were discovered by the elicitation and validation components of the study. Chemotherapy error rates (evaluated by our safety reporting system) declined during and after the project (p <.001). Conclusions: The initial elicitation methods and subsequent validation discussions supported rapid adoption of changes, improved communication regarding the process, and yielded error reduction. A combination of rigorous elicitation and validation methods creates increasingly accurate descriptions of complex but repetitive medical processes, leading to identification and removal of existing process defects while avoiding the creation of new defects as processes evolve.
The use of a palliative care tool in a community private practice.
Authors: Mahmood Tallat , Shock Helen , Severson Jane , Blayney Douglas W. ,   Michigan Oncology Quality Consortium Palliative Care Demonstration Project Lead Team
Published: February 2017

95

Background: Although symptom assessment is a routine part of oncology care, data from the Michigan Oncology Quality Consortium (MOQC) showed variation in individual practice (Health Affairs 31:718, 2012). As part of the MOQC Palliative Care Demonstration Project, we implemented the Edmonton Symptom Assessment System(ESAS) in a private oncology clinic. ESAS is a valid and reliable assessment tool that evaluates nine common symptoms experienced by cancer patients. Our target population was patients with active cancer undergoing chemotherapy. Methods: Initial implementation focused on patients of only one of the practice’s physicians. Symptoms rated >3 were considered symptomatic and were addressed by the physician. To monitor overall performance, a practice profile was compiled from the individual ESAS results. For symptoms with the greatest severity and incidence, targeted resources were developed and integrated in new electronic medical record templates and educational sessions with patients. Results: Managing change incrementally with weekly reassessment of implementation problems was effective. Use of the ESAS tool allowed for a focused discussion of the patient symptomatology and lead to better efficiency for the physician. Understanding the symptom burden of the patient population and implementing practice wide interventions helped to reduce the symptom burden at an individual patient level. Conclusions: The ease of use of the ESAS tool makes it highly successful in the private oncology practice setting. Profiling the symptom burden at a practice level facilitates targeted improvements and monitoring of performance over time. [Table: see text]
The value of a genetic counselor for patient identification.
Authors: Eichmeyer Jennifer N. , Zuckerman Dan Sayam , Beck Thomas M. , Camilo Nicolas , Sproat Patty , Burnham Christa
Published: February 2017

97

Background: Advances in genetics are rapidly changing cancer care and requiring institutions to maximize the unique skills of genetics professionals. The identification of genetic syndromes is vital for prevention and management of families with high cancer risks. Despite this high risk patients and families who qualify for genetic counseling are not referred; this is due to increasing responsibilities on physicians. Genetic counselors could be utilized to review new oncology charts to improve identification. Methods: A genetics assessment tool developed by NCI Community Cancer Centers Program generated baseline measurements of 2010 tumor registry data of patients meeting NCCN guidelines for genetics evaluation. A weekly list of new oncology patients was provided to a genetic counselor who reviewed each H&P dictation focusing on the pathology, age, and family history sections. The genetic counselor notified the oncologist by email or through the EMR system, and the physician discussed genetic counseling with patient or approved the order. Post implementation of the chart review program was measured using 2011 tumor registry data. Results: In 2010 58% of total applicable patients were offered a genetics evaluation. In 2011 this improved to 70%. Based on disease type: 69% (breast), 59% (colon), 29% (ovary), and 20% (uterine) were offered a genetics evaluation in 2010. In 2011 these numbers were 76% (breast), 64% (colon), 91% (ovary), and 20% (uterine). Over a 10-month period a total of 122 patients were identified through the chart review program by the genetic counselor. Three of these were confirmed to have a genetic mutation for one of the hereditary cancer syndromes. An average week included review of 73 charts for 10 medical oncologists, 4 radiation oncologists, 4 pediatric oncologists, which generated 60 to 80 minutes of work weekly for the counselor. Conclusions: This program improved patient identification and allowed physicians to become more aware of opportunities for genetic consultation that led to a streamlined referral process and allowed more applicable patients to receive counseling and testing. Project funded in whole or part with Federal Funds from the National Cancer Institute, National Institutes of Health, Contract No. HHSN261200800001E.
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.
Effect of adjuvant trastuzumab on locoregional recurrence in human epidermal growth factor receptor 2-positive breast cancer treated with post-mastectomy radiation therapy.
Authors: Lanning Ryan Michael , Riaz Nadeem , Morrow Monica , Moo Tracy-Ann , El-Tamer Mahmoud , Krause Kate , Chen Yu , Pei Xin , Powell Simon N. , Ho Alice Y.
Published: February 2017

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Background: HER2 overexpression is associated with an increased risk of LRR after mastectomy in the era prior to the use of adjuvant trastuzumab. The purpose of this study was to examine the effect of adjuvant trastuzumab on rates of LRR and whether this effect varied with the use of PMRT. Methods: From our institutional database, 474 women with Stage I-III HER2+ invasive breast cancer treated with mastectomy +/- adjuvant therapy from 1999-2007 were identified. Those patients lost to follow-up, treated with lapatinib, or diagnosed between 5/2004 to 5/2005 (when trastuzumab prescribing practices varied) were excluded; leaving 395 in the final study population. Two cohorts were compared: 139 women who received trastuzumab (5/2005-12/2007) and 256 women who did not (prior to 5/2005). Competing risks analyses were used to estimate cumulative incidence of LRR. Competing risks regression was used to evaluate the association between treatment factors and LRR. To minimize lead-time bias, patient data was censored at 5 years after mastectomy in both groups. Results: There were 18 LRRs in the entire cohort (16 no trastuzumab, 2 trastuzumab). Women in the no trastuzumab group were less likely to be node positive, receive chemotherapy or PMRT (all p<0.001). The hazard ratio for LRR was 0.218in the trastuzumab group (p= 0.04, 95% C.I. 0.05-0.94) with a 5-year risk of LRR of 1.5% in the trastuzumab versus 6.6% in the no trastuzumab group. After adjusting for PMRT and chemotherapy receipt, trastuzumab trended towards significance in decreasing LRR (p= 0.063). On subset analysis of 139 women who received PMRT, trastuzumab significantly reduced LRR (7.3% no trastuzumab, 0% trastuzumab, p=0.025). Among those who did not receive PMRT (256), trastuzumab did not significantly decrease LRR (6.3% no trastuzumab, 2.9 % trastuzumab, p=0.28). Conclusions: Adjuvant trastuzumab significantly reduced LRR in women with HER2+ breast cancer who received PMRT. A trend toward decreased LRR was observed in the entire population, but did not reach statistical significance, suggesting that the benefit is greater in HER2+ patients receiving multimodality therapy.
OSNA for detection of sentinel lymph node metastasis.
Authors: Suzuki Masahiko
Published: February 2017

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Background: SLN (sentinel lymph node) biopsy is a common procedure in surgical treatment of clinically node-negative breast cancer. OSNA (One-step nucleic acid amplification) is a semi-automated examination using molecular biological technique, and OSNA allows straightforward diagnosis of SLN metastasis without a pathologist by quantitative evaluation of CK19 m-RNA. The objective of this study was to confirm the reliability of OSNA for detection of sentinel Lymph node metastasis, and OSNA is also useful even in neoadjuvant chemotherapy (NAC) patients. Methods: Surgically obtained 159 SLNs from 106 breast cancer patients were evaluated and compared. The SLNs were sectioned into three pieces along the major axis. The central piece was sent to pathologists in an outside laboratory for postoperative histological investigation to diagnose metastasis. The other two pieces were examined with the OSNA to detecting metastasis during an operation. The OSNA analysis and the histological investigation were compared. Then, the patients were divided into two groups, one group was the patients with NAC (22 SLNs from 13 patients), and another group was the patients without NAC (137 SLNs from 93 patients). It was examined whether those concordance rates were similar. Results: 151 SLNs were same diagnosis using both methods. 4 SLNs were negative on OSNA but positive on histology, and these 4 SLNs contained only micrometastasis lesion. Other 4 SLNs were positive on OSNA but negative on histology. The concordance rate was 95.0%. In the patients with NAC, 20 SLNs were same diagnosis. Two SLNs were negative on OSNA but positive on histology, and these 2 SLNs were micrometastasis. The concordance rate was 90.9%. In the patients without NAC, 131 SLNs were same diagnosis. 2 SLNs were positive on OSNA but negative on history, and these 2 SLNs were micrometastasis. 4 SLNs were positive on OSNA but negative on history. The concordance rate was 95.6%. Conclusions: The concordance rate in patients with NAC was as high level as the rate in patients without NAC. The false negative SLNs were all micrometastasis. These results suggest that OSNA is very useful for detecting SLN metastasis and it is clinically acceptable in NAC patients.
Safe negative-margin width in breast-conservative therapy: Results from a population with a high percentage of negative prognostic factors.
Authors: Bhatti Abu Bakar Hafeez , Khan Amina Iqbal , Aamir Muhammad Awais , Shah Mazhar Ali , Siddiqui Neelam , Muzaffar Narjis
Published: February 2017

75

Background: There remains a controversy in literature regarding adequate width of negative surgical margins in breast conservative therapy (BCT). Majority of patients included in studies on outcomes of BCT had favorable prognostic factors. Pakistani population is known to have an elevated expression of unfavorable prognostic factors. This study was done to determine safe negative margin width in a patient population with significantly higher percentage of unfavorable prognostic factors undergoing BCT. Methods: A review of patients who received BCT from 1997-2009 at Shukat Khanum Cancer Hospital was performed. A total of 603 patients whose margin status could be assessed were included. Patients were divided into close ( ≤ 2mm), free (> 2-10mm), and wide (> 10mm) margin groups. Patient characteristics, medical treatment modalities, and number of locoregional recurrences were observed for each margin group. Chi square and Fisher’s exact test were used for categorical variables. Five year locoregional control was determined for margin groups. Univariate and multivariate Cox regression analysis was performed to determine independent predictors of locoregional recurrence. Results: Out of total, 415 (69%) patients were <50 years of age. There were 82 (15%) T3/T4, 337 (56%) poorly differentiated and 238 (39%) ER/PR–ve tumors. Nodal positivity was present in 314 (52%) patients. A higher percentage of T3/T4 tumors in close margin group (25% versus 13% and 7%) (p < 0.0001) was observed. Use of neoadjuvant chemotherapy was significantly higher in close margin group (33% versus 29% and 16%) (p < 0.0001). The actual number of observed locoregional recurrences was 16 (12%), 8 (3%), and 10 (4.6%) in close, free, and wide margin groups (p = 0.002) while the expected 5 year locoregional control was 90%, 97%, and 96% (p = 0.002) respectively. On multivariate analysis tumor size stage, nodal involvement and negative margin width were independent predictors of locoregional failure. Conclusions: A negative margin width of 2mm might represent an adequate negative margin width in populations with a higher percentage of unfavorable prognostic factors.