bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation sequencing (NGS) in metastatic breast cancer (mBC) patients: Translation from sequence data into clinical practice.
Authors: Moreira Raphael Brandao , Peixoto Renata , Sousa Tercia Tarciane Soares de , Cruz Marcelo , Maluf Fernando , Buzaid Antonio 
Published: February 2017

133 Background: A considerable number of patients with mBC progress after exhausting all approved standard therapies but maintain an adequate performance status and could be candidates for further treatment. We aim at reviewing our experience with the use of a NGS platform in refractory mBC and its clinical utility. Methods: We retrospectively reviewed demographics, NGS results, and the suggested therapies received by patients undergoing NGS (Foundation Medicine, Cambridge, MA, USA): exonic sequencing of 315 genes and selective intronic sequencing from 28 genes for refractory mBC. Co-primary endpoints were the percentage of patients with targeted therapy options uncovered by mutational profiling and the percentage of them who received genotype-directed therapy. Results: Samples from 20 patients were tested. Histologic subtype consisted of triple negative (50%), HER 2 +, hormonal receptor [HR] - 15%, HR + and HER 2 - (35%). A targetable genomic alteration was identified in 14 (70%) patients, most frequently in TP53 (11 [55%]), PIK3CA (8 [40%]), FGFR1 (4 [20%]), CCND1 (3 [15%]), PTEN (3[15%]) and BRCA2 (2[10%]). Therapy could be personalized in 9 (45%) of 14 patients. Of the 9 patients who were received targeted therapy, 7 (77%) had an objective response and had stable disease for more than 3 months. Conclusions: Mutational profiling using a targeted NGS panel identified potentially actionable alterations in the majority of advanced breast cancer patients. The assay provided clinical benefit in 35% of the patients.
uPA receptor and its interaction partners: Impact as potential therapeutic targets in triple-negative breast cancer.
Authors: Aubele Michaela , Huber Michaela Christina , Falkenberg Natalie , Gross Eva , Braselmann Herbert , Walch Axel Karl , Schmitt Manfred 
Published: February 2017

150 Background: Triple-negative breast cancers (TNBC), which lack expression of estrogen (ER), progesterone (PR), and HER2 receptors are characterized by tumor tissue expression of the urokinase-type plasminogen activator receptor (uPAR) system. Methods: We evaluated uPAR and its interaction partners (uPAR-interactome) by immunohistochemistry (IHC) in tissue microarrays (TMA) prepared from ~300 TNBC tumor tissue specimens and in the TNBC model cell lines BT549 and MDA-MB231. Protein expression of 25 different factors constituting the uPAR-interactome was evaluated by IHC; several of the uPAR-protein complexes were identified employing the proximity ligation assay (PLA). Results were correlated with histomorphological parameters and survival of the patients. RNA interference was employed in the TNBC cell lines for several of the parameters assessed. To analyze effects of uPAR and/or uPA depletion on malignant cell behavior, proliferation, migration, and invasion assays as well as Western blot, PLA, immunoprecipitation, mass spectrometry, and immunohistochemistry were conducted. Results: After downregulation of uPAR and uPA in TNBC cell lines, significantly reduced cell proliferation, invasion, and migration were observed. Furthermore, interaction between uPAR and IGF1R (insulin-like growth factor1 receptor) was shown, and several novel interaction proteins of uPAR could be identified, such as Cyr61 (cysteine-rich angiogenic inducer61). In TNBC tumor specimens, association between uPAR expression and histological grade plus expression of cathepsin B, IGF1R, IR (insulin receptor), and plasminogen was shown. Expression of KLK4 (stromal) and Ki67 was correlated with disease-free survival of the patients. Presence of uPAR/IGF1R protein complexes was associated with histological grade, with the expression of PAI-1, Ki-67, p27, and cathepsin B. Conclusions: Our findings demonstrate that uPAR and its interacting partners, expressed in TNBC tumor tissues, may be considered as potential novel therapeutic targets for this fatal disease.
Age, race, BMI, and pathologic complete response following neoadjuvant chemotherapy: An analysis of four alliance clinical trials.
Authors: Warner Erica T , Ballman Karla V. , Buzdar Aman , Carey Lisa A. , Sikov William M. , Strand Carrie , Partridge Ann H. 
Published: February 2017

33 Background: Pathologic complete response (pCR) is an important prognostic indicator and surrogate endpoint, particularly for patients with hormone receptor-negative breast cancer. Previous studies have suggested differential response to pre-operative therapy by age and body mass index (BMI), though no association has been seen by race. We assessed associations of age at diagnosis, BMI and race with pCR accounting for breast cancer subtype. Methods: Women enrolled in four clinical trials of neoadjuvant chemotherapy (CALGB 40601 and 40603; ACOSOG Z1031 and Z1041) were eligible for this analysis. Age, race, and BMI were abstracted from patient records at baseline. Tumor subtype was assessed using immunohistochemical staining and/or fluorescence in situ hybridization. Logistic regression models were used to determine the association of race/ethnicity and age at diagnosis with pCR, the absence of residual invasive disease in the breast after neoadjuvant chemotherapy, adjusting for subtype (HER2+, ER+/ HER2-, triple negative), age, study arm, lymph node status, tumor size, and tumor grade. Results: 1,146 women with a mean age of 51.5 years were included. 156 (13.6%) were of black race. 590 (51.5%) of tumors were HER2+, 169 (14.7%) were ER+/HER2- and 387 (33.8%) were triple negative. In multivariate analyses controlling for tumor characteristics and other factors, black race (OR: 1.07, 95% CI: 0.67-1.70), age (OR: 0.99, 95% CI: 0.97-1.00) and BMI (OR: 0.99, 95% CI: 0.96-1.01) were not significant predictors of pCR. Similar associations we observed when stratified by subtype, and we found no interaction between age and black race (p=0.06), black race and BMI (p=0.54) or age and BMI (p=0.73). Conclusions: After accounting for tumor characteristics, we observed no differences in pCR rates according to race, age or BMI.
Concordance of Van-Nuys Prognostic Index, Memorial Sloan Kettering Breast Cancer nomogram and Oncotype Dx DCIS scores in prediction of ductal carcinoma in situ(DCIS) recurrence risk.
Authors: Matlock Kinzie , Lloyd Jillian M. , Carter W. Bradford , Grujic Edina , Frazier Thomas G. 
Published: February 2017

56 Background: Ductal Carcinoma in situ (DCIS) has a wide spectrum of bioagressiveness. Three models used to assess recurrence risk (RR) of DCIS include: the Van-Nuys Prognostic Index (VN), Memorial Sloan Kettering Breast Cancer Nomogram (MN) and Oncotype Dx DCIS Score (OD; Genomic Health, Redwood City, CA). The aim of our study was to evaluate the concordance between these RR models. Methods: An IRB-approved retrospective chart review was performed on 37 consecutive patients at our institution with DCIS from 12/2011-4/2015 who underwent breast conservation surgery and in whom an OD was obtained. The OD and ‘any recurrent event at 10-years’ scores were used to stratify patients into low risk (LR; OD DCIS score <39/<17%), intermediate risk (IR; 39-54/17-24%) and high risk (HR; >54/>24%), as outlined in the original OD study. The ‘10-year RR’ scores from MN were stratified using the same percentile breakdown as OD. The VN were stratified into LR (4-6), IR (7-9) and HR (>9) groups based on the updated VN study’s guideline. Pathologic slides were re-reviewed by one pathologist blinded to OD score to determine size and margin width based on the protocol outlined in the original VN paper. The three scores for each patient were compared. Results: Eleven patients (29.7%) had concordance between all three scores and all were LR. In 10.8% of patients, there was no concordance between the three scores. The concordance between the OD and VN, OD and MN, and VN and MN was 64.9%, 48.6% and 35.1%, respectively. Conclusions: In evaluating RR, determining LR may have the greatest implication since this group may be the least likely to benefit from adjuvant radiotherapy. Concordance between all three models was seen only in LR patients. All patients who were LR by VN were also LR by OD and MN. Determining a VN initially may help guide additional testing. The added value of OD may be primarily in patients who are not LR by VN. The MN seems to be of limited value in this study. Larger studies assessing these relationships and their outcomes in predicting potential RR in DCIS are warranted.
Development of a new photonumeric scale for acute radiation dermatitis in patients with breast cancer.
Authors: Shumway Dean , Walker Eleanor M. , Kapadia Nirav S. , Do Thy Thy , Griffith Kent A. , Feng Mary Uan-Sian , DePalma Bonnie , Helfrich Yolanda R. , Gillespie Erin , Miller Alexandria , Jagsi Reshma , Pierce Lori J. 
Published: February 2017

86 Background: The Common Terminology Criteria for Adverse Events (CTCAE) is frequently used to grade the severity of acute radiation dermatitis (ARD), but has not been validated despite decades of clinical use. We sought to develop a photonumeric scale to consistently describe ARD in breast cancer patients undergoing radiation (RT). Methods: Patients enrolled on a prospective study that included photographs and quantitative measurements of erythema and hyperpigmentation using colorimetry. 209 photographs from 35 patients with white skin and 369 photographs from 50 patients with skin of color were used to develop two photonumeric scales. Predominant erythema (in white skin) OR hyperpigmentation (in skin of color) were rated on a 4 point scale, with grading of desquamation on a separate 3 point scale. Four raters used both CTCAE and photonumeric scales to independently score all photographs. Intra- and inter-rater agreements were assessed using weighted kappa scores. Results: Using the CTCAE, 95% of photos were rated as grade 1 or 2. There was a trend toward higher grade in patients with skin of color, with grade 2 toxicity in 43% vs. 24%. Intra-rater agreement for CTCAE ratings was 65—87% (kappa 0.34—0.67), with a wide range of inter-rater agreement (56—81% agreement fraction, kappa 0.04—0.58). Using the photonumeric scale, intra-rater agreement was high for erythema/hyperpigmentation in patients with white skin (74—82%, kappa 0.49—0.70) and skin of color (69—86%, kappa 0.55—0.79), along with desquamation (78—87%, kappa 0.52—0.66). There was moderate inter-rater agreement for erythema/hyperpigmentation (51—82%, kappa 0.15—0.71) and desquamation (63—88%, kappa 0.36—0.58). Colorimetric measurements correlated strongly with photonumeric grade. Conclusions: We report a new photonumeric scale for ARD in breast cancer patients with satisfactory reliability across the spectrum of skin pigmentation. Intra-physician ratings were consistent, with moderate inter-physician agreement. The CTCAE functions as a binary scale, with 95% of ARD rated as grade 1 or 2 toxicity. Future work includes correlation with patient-reported outcomes and physician ratings at the point-of-care. Funded by a Munn Idea Grant (G011480).
Encouraging regular physical activity for hormone-receptor positive breast cancer patients to improve mental and physical health during treatment and survivorship.
Authors: Jordan Corinne , Klepsa Alicia 
Published: February 2017

91 Background: Physical inactivity has direct effects on risk of chronic diseases, mental health, quality of life, and early mortality. Women that engage in physical activity after a breast cancer diagnosis may reduce the risk of recurrence and death from this disease. This study examines postmenopausal women with clinical stage I or II breast cancer using the Patient Reported Outcome Measurement Information System (PROMIS) 10 – Global Health Survey, Fitbit Flex, and regular Wellness Coaching. Methods: Our prospective study follows clinical stage I/II, postmenopausal, ER+, Her2- women with BMI > or = to 25 beginning at their surgical consultation. Visits occur again post-operatively, six months after consultation, and again at one year. Each patient was given a Fitbit Flex with the expectation to complete 7,000 steps daily, and weekly Wellness Coaching. At each visit, a record of their activity was recorded including steps, heartrate, blood pressure, and body mass index. Quality of life was also assessed using PROMIS 10 - Global Health Survey. Results: 19 patients have enrolled. 100% of patients on study had BMI stay the same or decrease from initial consult to postop visit. 66% gained weight from initial postop visit to 6 months. 47% of patients met the daily goal of 7,000 steps. 80% showed significant increase in mental health scores and 60% increased physical health scores by PROMIS 10. Conclusions: Encouraging regular physical activity during treatment and survivorship for breast cancer can improve mental health and physical well-being during breast cancer treatment. Regular wellness coaching can support patients to reach their physical and mental health goals during treatment and survivorship.
3 Steps 4 Health, a program on quality of life.
Authors: Fonfa Ann 
Published: February 2017

95 Background: As Patient advocates we have spent years gathering/ sharing information about simple, natural strategies to reduce risk of cancer treatment-related toxicities and strengthen the immune system. Methods: We created a simple 3 step program that absolutely anyone with cancer, at any stage, can incorporate into their own healthful protocol. Since it involves no tools and can be used at the level that an individual is at the time they start, we consider it appropriate for all. Further we cannot see any objection from the Oncologist or staff members. Step 1 is eating one more fruit and one more vegetable every day. This is helpful since studies show few Americans are getting enough fruits or vegetables. The National Cancer Institute considers ‘Five a Day’, a minimum. We want to get people started on the correct path simply and easily. Step 2 is taking a walk around the room, facility or neighborhood depending on ability and health status. This has been shown by many studies to help anyone with cancer, undergoing treatment or in recovery. We are not asking folks to become athletes; we are involving them in a plan to improve their health. Step 3: 7 deep breaths before treatment, in a stressful situation or at bedtime. This step is important to reduce stress and encourage relaxation. Results: Every step moves people forward into better health. We believe taking these first steps will lead to more healthful behaviors, better ability to handle conventional cancer treatments, and an easier recovery. Conclusions: Immune system health depends on the individual as much as any treatments. In this era of Immunology, we see a real opportunity for our Patient/Advocate-driven concept.
Symptom burden in hospitalized patients with advanced cancer.
Authors: Moran Samantha M.C. , El-Jawahri Areej , Pirl William F. , Traeger Lara , Kumar Pallavi , Ryan David P. , Lennes Inga Tolin , Cashavelly Barbara J. , Martinson Holly S , VanDusen Harry , Hochberg Ephraim P. , Jackson Vicki A. , Greer Joseph A. , Temel Jennifer S. , Nipp Ryan David 
Published: February 2017

100 Background: Patients with advanced cancer experience high rates of both physical and psychological morbidity, but data describing patients’ symptoms during hospital admissions are lacking. We sought to describe symptom burden in hospitalized patients with incurable solid and hematologic malignancies. Methods: We prospectively enrolled patients with incurable cancers admitted to the Massachusetts General Hospital from 9/1/2014 through 5/1/2015. Within the first week of their admission, we assessed physical and psychological symptoms using the Edmonton Symptom Assessment System-revised (ESAS-r). Beginning 11/15/2015, we also administered the Patient Health Questionnaire 4 (PHQ-4), scored categorically. Results: We enrolled 457 of 547 (84%) eligible patients. Participants (mean age=63.8 years; n=231, 51% female) had the following malignancies: gastrointestinal (n=149, 33%), lung (n=77, 17%), genitourinary (n=52, 11%), breast (n=33, 7%), hematologic (n=24, 5%), and other solid tumors (n=122, 27%). Using the ESAS-r, tiredness, drowsiness, anorexia, and pain were the most common severe symptoms. Using the PHQ-4, approximately one-third of participants screened positive for depression (91/271, 34%) and anxiety (86/273, 32%). Conclusions: Hospitalized patients with incurable solid and hematologic malignancies experience substantial physical and psychological symptoms. Most patients reported at least moderate tiredness, drowsiness, anorexia and pain. Additionally, a concerning proportion reported depression and anxiety. Our data demonstrate the need for efforts to alleviate the physical symptoms experienced by this population, while also seeking to understand and address their psychological needs. [Table: see text]
How do palliative care needs vary across the disease trajectory in patients with gynecologic cancer?
Authors: Ruskin Rachel , Rowland Michelle Renee , Moore Katherine N , Lefkowits Carolyn , Walter Adam , Slaughter Katrina , Landrum Lisa Michelle , Walker Joan L. , Matzo Marianne 
Published: February 2017

106 Background: The WHO’s integrated model emphasizes that palliative care (PC) should be provided concurrently with curative and life-prolonging care, with disease-directed treatments decreasing and PC increasing over time. This study aimed to understand how accurately this theoretical model matches the PC needs of gynecologic cancer (GC) patients. Methods: GC patients at a comprehensive cancer center completed a symptom and needs assessment questionnaire as part of routine care. Needs were divided into physical, emotional, social, practical, and informational domains. Patients reporting at least one symptom score ≥ 4/10 made the physical need domain positive. For the remainder of the categories, patients endorsing at least one need in a given domain made that domain positive. Time points in the illness trajectory were categorized as diagnosis, primary treatment, remission, and progression/recurrence. Univariate analyses were utilized to assess differences in needs at various time points. Results: Questionnaires from 1348 patient visits over 3 months were included. Patients had ovarian (39%), uterine (36%), cervical (16%), and vulvar (5%) cancer. Visits occurred around the time of diagnosis (6%), during primary therapy (28%), during remission (42%), and during disease progression or recurrence (23%). Physical needs were most common at diagnosis and during progression/recurrence (p < 0.01). Emotional needs (p < 0.01), social needs (p < 0.01), and informational needs (p < 0.01) all varied throughout the course of disease and were highest at diagnosis. At each time point, at least 65% of patients had one or more PC needs. Having needs in multiple domains ( ≥ 3) was associated with time point, with patients around the time of diagnosis having the highest rate of need in multiple domains (p < 0.01). Conclusions: GC patients have a broad range of PC needs across the trajectory of their illness. The WHO schema fails to capture the full scope of these needs and under-appreciates their prevalence earlier in the course of the disease. These results underscore the importance of training gynecologic oncologists in primary PC as well as increasing referrals to specialist PC providers.
The acceptability to African-Americans of a structured conversation guide to improve advance care planning in the setting of cancer: A focus-group study.
Authors: Sanders Justin J , Sterba Katherine W. , Ford Dee , Block Susan 
Published: February 2017

11 Background: African-Americans are less likely than whites to participate in advance care planning (ACP), which may contribute to disparities in the receipt of goal-concordant care. Literature points to multiple factors: the impact of religion, mistrust, different preferences for life-sustaining measures, family-decision making styles and poor knowledge about ACP. Early ACP conversations are associated with improved outcomes at the end of life, including goal-concordant care. A systematically-developed, serious illness conversation guide (“guide”) for oncologists, embedded in a systems-based approach to improving illness care, has demonstrated more frequent, higher-quality, and earlier ACP conversations in a predominantly white and middle class cohort of cancer patients. This study aimed to explore the acceptability and need for modification of the guide in more diverse populations. Methods: We conducted a series of focus groups with panels of clinicians and researchers, African-American church members, and seriously ill patients and their caregivers to assess barriers to ACP and preferences concerning modifications to the guide. We used template analysis to code themes at the individual, interpersonal and systems levels. Results: At the individual level, participants confirmed the importance of religion and the impact of perceived discrimination (e.g., receipt of inferior care) and superstition (e.g., talking about death may make it happen). Interpersonal-level factors influencing ACP included family, trust, and concerns about provider abandonment. Participants confirmed systems-level barriers of access and mistrust in the healthcare system and highlighted community outreach as a key part of the process. Participants reported positive responses to the tone and content of the guide and found the guide to be acceptable when it included a question that elicited coping mechanisms, including religion. Conclusions: Participants in our study found the use of a serious illness conversation guide to identify patient goals and priorities acceptable, and emphasized the importance of adding a question focused on coping and religion.