tbuckley/cabot-search huggingface dataset:
Breast cancer screening practices with high-risk women: A cross-sectional survey.
Authors: Anne Hudson Blaes, Rachel Isaksson Vogel, Nancy Raymond, Kristine Talley, Alicia Allen, Rebekah Nagler, Deanna Gek Koon Teoh, Susan Mason, Jean Wyman
Journal: Journal of Clinical Oncology (2017)

1550 Background: Little literature exists on primary care providers’ knowledge and preferences towards breast cancer screening for high-risk women. While guidelines recommend MRI and mammography, it is unclear how frequently these recommendations are used. Methods: This web-based survey of providers licensed to practice in Minnesota was conducted. This analysis focuses on breast cancer screening practices for high-risk women. Data were summarized using descriptive statistics; professional characteristic comparisons were conducted using Chi-squared tests. Results: 805 of 10,392 (8%) invitees completed the survey. 72.2% were female. 43.9% were physicians (20.8% internists, 71.7% family medicine, 6.3% gynecology), 11.4% physician assistants (PAs), 44.8% advanced practice registered nurses (APRNs). 84.8% were in community practice, 38% &gt; 20 years of experience and 27.1% &lt; 10 years. When asked how effective screening was for reducing cancer mortality in high risk women, mammography was thought to be very effective (48.8%) or effective (46.8%) in women ages 40-49 years, for women ages 50+ years, 60.8% and 35.7%, respectively. 62.4% thought breast MRI was very effective in reducing cancer mortality in high risk women. There was no difference in breast MRI recommendation based on professional background, experience or practice setting. Female practitioners, less experience, and those working in gynecology or women’s health were more likely to recommend breast MRI. A case vignette for high risk screening cancer survivors is provided (Table). Conclusions: Most primary care providers believe mammography is helpful in women at high risk for developing breast cancer. Less than half of practitioners, however, are following guideline specific recommendations of both mammography and MRI for breast cancer screening in high-risk patients. [Table: see text]
Cancer susceptibility mutations in individuals with breast and ovarian cancer using next-generation sequencing.
Authors: Kenneth Offit, Kasmintan A Schrader, Kara Noelle Maxwell, Joseph Vijai, Steven Hart, Tinu Thomas, Bradley Wubbenhorst, Vignesh Ravichandran, Raymond Moore, Chunling Hu, Jenna Lilyquist, Hermela Shimelis, Thomas Paul Slavin, Susan M. Domchek, Mark E. Robson, Csilla Szabo, Susan L. Neuhausen, Jeffrey N. Weitzel, Fergus J. Couch, Katherine L. Nathanson
Journal: Journal of Clinical Oncology (2016)

1515 Background: Germline mutations of BRCA1 and BRCA2 underlie joint susceptibility to breast and ovarian cancers, but do not account for all cases; other genes involved in homologous recombination DNA repair have been implicated in the germline and somatic setting. Multiplex germline genetic testing and sequencing of tumor and normal DNA are broadening the phenotypes of well-established cancer predisposition syndromes. Methods: Whole-exome sequence data generated from germline DNA of 73 individuals with a history of metachronous breast and ovarian cancers (BRCA1/2 uninformative) were analyzed to identify presumed pathogenic germline variants (PPGV) in 151 known cancer susceptibility genes. Results: Twenty-three cases (31.5%) harbored 1 or more PPGV in one of the 151 cancer susceptibility genes. Twelve cases (16.4%) harbored 1 or more PPGV with minor allele frequencies (PPGV-MAF) <0.01% in BRCA1, PALB2 (n=2), RAD50, RAD51D, TP53, BARD1, ATR, PPM1D, SMARCB1, PRF1, and COL7A1. An additional eleven cases plus one overlapping case, (16.4%) harbored 1 or more PPGV-MAF>0.01% in GJB2 (n=3), SERPINA1 (n=2), FANCL (n=2), MUTYH (n=2), HFE (n=2), RAD51D, and BLM. Several of the recurrent variants observed are known founder mutations and act as validation that filtering criteria designed to eliminate recurrent variants was not too stringent. All variants were heterozygous. Variants in genes associated with cancer risk in the autosomal recessive setting (PRF1, SERPINA1, MUTYH,FANCL,HFE) are not anticipated to have contributed to the cancer phenotype. However, further tumor studies and comparison to control cohorts will help elucidate their relevance. Conclusions: These data demonstrate that PPGV in known breast and/or ovarian cancer susceptibility genes, as well as other cancer susceptibility genes, can be detected by massively parallel sequencing of individuals metachronously affected with both breast and ovarian cancers. Further characterization of the role of PPGV in the etiology of these tumors will require correlations with matched tumor genomes, co-segregation in kindreds, and functional analysis.
Phase II trial of CC-486, a DNA methyltransferase inhibitor, in combination with fulvestrant in postmenopausal women with ER+, HER2- metastatic breast cancer who have progressed on an aromatase inhibitor (AI).
Authors: Mario Campone, Luca Gianni, Javier Cortes, Thaddeus Beck, Julieann Miller, Peng Chen, Abderrahim Fandi, Jasgit C. Sachdev
Journal: Journal of Clinical Oncology (2016)

TPS616 Background: The HR+/HER2- subtype comprises ~70% of all breast cancers. Sequential endocrine therapy with SERMS ( tamoxifen), AIs (letrozole, anastrozole, exemestane), and SERDs (fulvestrant) are recommended for pts with HR+ metastatic breast cancer (MBC). However, development of resistance to endocrine therapy poses a major problem in the use of these agents. CC-486, an oral epigenetic modifying agent, is hypothesized to potentially restore sensitivity to endocrine therapy. This Phase II study will evaluate the efficacy of CC-486 in combination with fulvestrant in pts with ER+/HER2- MBC who have progressed on an AI. Methods: Approximately 92 pts will be randomized 1:1 to receive CC-486 300 mg orally on days 1 - 21 of each 28-day cycle plus fulvestrant 500 mg IM on days 1 and 15 in the first cycle and day 1 in cycles ≥ 2 or fulvestrant 500 mg on days 1 and 15 in the first cycle and day 1 in cycles ≥ 2. Key eligibility criteria include age ≥ 18 years, postmenopausal, metastatic disease, ER+/HER2− disease refractory to treatment with an AI defined as recurrence on or ≤ 12 months after prior AI treatment in the adjuvant setting or disease progression on or ≤ 1 months of prior treatment with an AI in the metastatic setting, ECOG PS 0 – 1 and measurable disease by RECIST v1.1. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall response rate, clinical benefit rate, overall survival, duration of response, and safety. Exploratory endpoints include molecular profiling of the tumor for evaluation of predictors of clinical outcome. Efficacy will be evaluated every 8 weeks during the first 24 weeks and then every 12 weeks until disease progression, unacceptable toxicity, death, or new therapy. The primary efficacy analysis will be performed after 70 PFS events are documented. The first safety analysis will be conducted after 32 patients have completed ≥ 1 cycle of treatment. The trial is open for enrollment; 56 pts have been enrolled to date. Clinical trial information: NCT02374099.
Variation in screening rates in a multi-ethnic population-based study in Chicago.
Authors: Brisa Aschebrook-Kilfoy, Muhammad Ghulam Kibriya, Brian C-H Chiu, Dezheng Huo, Marcy A List, Elizabeth Stepniak, Golam Sarwar, Rabab Al Shams, Rajan Gopalakrishnan, Michelle M. Le Beau, Habibul Ahsan
Journal: Journal of Clinical Oncology (2017)

1509 Background: We initiated the Chicago Multiethnic Prevention and Surveillance Study (COMPASS) in 2013. Here, we present screening rates for key cancers with known disparities in risk/and or outcomes in Chicago, considering the effect health care access and race/ethnicity, and we compare the findings in COMPASS to rates reported by the CDC. Methods: COMPASS participant responses to a health interview were analyzed. The analysis of colorectal cancer screening (CRCS) was limited to persons 50-75, mammography screening (MS) was restricted to women ages 50-74, and cervical screening (CS) by pap smear testing was restricted to women ages 21-65. Frequency statistics and linear regression models were run to evaluate associations. Results: A total of 2,967 COMPASS participants were included in the analysis from 18 communities. We found ever CRCS rates in Chicago are lower than the national average (52.3% vs. 58.6%; p &lt; .01) and that CRCS is lower in blacks (50.3%) and Hispanics (52.1%) compared to whites (65.8%), and that those with health insurance (HI) report a CRCS rate of 56.8% compared to 25.5% without insurance. Mammography within the last 2 years was 70.8% in COMPASS women compared to 72.4% nationally, with black women reporting higher rates of MS in the past 2 years (73.0%) compared to white women (65.4%) and Hispanic women (62.9%); and higher MS among women with HI (74.2%) compared to women without HI (47.2%). Pap screening within the last 5 years was 84.3% in COMPASS women compared to 83.0% nationally (last 3 years), with both black (85.3%) and Hispanic (83.2%) women reporting non-significantly higher CS compared to white women (80.9%) in COMPASS, and significantly higher CS among women with HI (86.2%) compared to women without HI (77.7%). Conclusions: Our results reinforce the fact that differences in cancer screening reflect the larger problem of access to care. We further found racial disparities in CRC screening in COMPASS to be consistent with disparities in incidence. However, our results do not support the notion that the disproportionate burden of breast and cervical cancer in black and Hispanic women in Chicago are primarily due to a lack of screening.
Changes in the immunoregulatory gene profile in ibs subjects following probiotic treatment: investigating a mechanism of action
Authors: E Bairead, J MacSharry, P Scully, A Fanning, B Kiely, S O'Mahony, F Shanahan, L O'Mahony, E Quigley
Journal: Endoscopy (2006)

Aims: Previous studies have demonstrated the efficacy of Bifidobacterium infantis in providing relief in IBS. A randomised, double-blind, placebo controlled study was instigated to investigate possible immunological alterations following oral administration of Bifidobacterium infantis, to determine potential causes for this therapeutic response at the molecular level and establish a possible mechanism of action.
Simultaneous detection and quantification of BKV-, JCV- amd SV40-DNA in renal transplant recipients.
Authors: F Giacchino, M Bergallo, C Merlino, C Costa, F Sinesi, F Piana, E Burdino, F Bonello, Gp Segoloni, R. Cavallo
Journal: Journal of the American Society of Nephrology (2006)
Brain tumors: Regulation of angiogenesis.
Authors: Eduard Evgenevich Rostorguev, Elena Mikhaylovna Frantsiyants, Yulia A. Pogorelova, Natalia D. Cheryarina, Larisa Kozlova, Lyudmila Dmitriyevna Tkalya, Irina Stasio Tavaryan, Dmitriy P. Atmachidi, Sergey E. Kavickij, Natalya S. Kuznetsova, David H. Porksheyan, David H. Porksheyan, Oleg I. Kit
Journal: Journal of Clinical Oncology (2017)

e13540 Background: Cancer implicates pathological angiogenesis. The problem of treatment for primary and metastatic brain tumors is still unsolved. In addition to main angiogenic functions, VEGF family performs important mediator functions in the immune system. The role of VEGF family in central nervous system tumors is poorly studied. Our purpose was to study the levels of factors of angio- and lymphangiogenesis in tissues of glioblastomas (G), brain metastases (MTS), meningiomas and corresponding peritumoral area. Methods: Tissues of tumor and peritumoral zone (PZ) obtained during the surgery from 22 patients with G, 14 patients with brain MTS from breast cancer and 12 meningioma patients, mean age 39.2±4.8 years, were studied. Levels of VEGF-A, VEGFR-1, VEGF-C and VEGFR-3 were determined by ELISA. The data were processed using Statistica 10 program. The significance of differences was determined by Student's t-test. Results: VEGF-A levels in tissues of G and MTS were higher than in meningioma tissues by 74.7 and 94.5 times, respectively; levels of VEGF-R1 were 2.7 and 3.9 higher, and the VEGF-A/VEGF-R1 coefficient was 28.1 and 24.1 times higher, respectively. Levels of VEGF-C and VEGF-R3 were escalated only in G tissues compared to meningiomas (by 1.7 times on average). The VEGF-С/VEGF-R3 coefficient was similar in all studied tumors. VEGF-A levels were higher in PZ of G and MTS compared to PZ of meningiomas – by 78.2 and 110.7 times, respectively, while VEGF-R1 level was higher in G PZ only (by 5.5 times). The VEGF-A/VEGF-R1 coefficient was 14.5 and 128.5 times higher, respectively. VEGF-C level in PZ of G was escalated compared to meningiomas by 6.5 times, in MTS – by 1.6 times. VEGFR-3 contents did not differ significantly in all PZ samples, but the VEGF-С/VEGF-R3 coefficient was higher in PZ in G by 9 times and in MTS by 2 times. Conclusions: Compared to benign meningiomas, angio- and lymphangiogenesis are activated in glioblastoma tissue and angiogenesis – in metastatic tissue. Lymphangiogenesis is more active in peritumoral zone of glioblastomas compared to metastatic tissue, and angiogenesis is more active in peritumoral zone of metastases.
Abstract 12659: Autologous Mesenchymal Stem Cells Produce Concordant Improvements in Regional Function, Tissue Perfusion, and Fibrotic Burden when Administered to Patients Undergoing Coronary Artery Bypass Grafting
Authors: Vasileios Karantalis, Darcy L DiFede, Gary Gerstenblith, Si Pham, James Symes, Juan Pablo Zambrano, Joel Fishman, Pradip Pattany, Ian McNiece, John Conte, Steven Schulman, Katherine Wu, Ashish Shah, Elayne Breton, Janis Davis-Sproul, Richard Schwarz, Gary Feigenbaum, Muzammil Mushtaq, Viky Y Suncion, Al Lardo, George Rich, Ivan Borrello, Adam Mendizabal, Tomer Z Karas, John Byrnes, Maureen Lowery, Alan W Heldman, Joshua M Hare
Journal: Circulation (2013)

Background: There is evidence supporting the efficacy of cell-based therapy to improve LV function in patients with chronic ischemic cardiomyopathy undergoing CABG. The precise impact of this strat...
Changes in clinical management following genomic testing in patients who have already undergone multiple oncological treatments.
Authors: Rishi Patel, Shawn C. Shambaugh, David E. Kanamori, Richard Kim-Thean Ng, Puneet Singh, Pradip K. Rustagi, Ajay Desai, Giridhar R. Gorla, Alan D. Cartmell
Journal: Journal of Clinical Oncology (2016)

e13028 Background: Genomic testing of malignancies is becoming an area of increasing clinical significance. Multiple agencies now offer testing along with a list of trials and FDA approved treatments directed towards the various gene alterations found. We decided to explore how often genomic testing leads to changes in the management for 37 patients with various malignancies. Methods: 37 patients that had already undergone a multitude of treatments were tested to explore remaining options using a multigene panel in a CLIA approved laboratory. Results: Testing revealed 141 gene alterations. Of these alterations, 94 were actionable leading to 187 trial options and 100 FDA approved treatments. Despite these promising figures, genetic testing resulted in a change in management for only 8 patients. Of note, there were 4 patients who did not have any actionable genetic alterations. Of all malignancies, breast cancer garners the largest number of options in regards to both trials and FDA approved treatments. Conclusions: Given the data gathered, it seems that while there are many actionable genes, testing currently does not lead to a high number of changes in management. While clinical management did not change in a large proportion of patients, given exhaustion of all other options, genomic testing is a reasonable next step. In the coming months, it will be interesting to explore the cost benefit analysis of said genomic testing as it relates to changes in outcome.
Real-world use of first-line chemotherapy in post-menopausal patients with HR-positive HER2-negative metastatic breast cancer (mBC) in a US community oncology network.
Authors: Debra A. Patt, Xiaolong Jiao, Eileen Fonseca, Jamyia Clark, Patricia S. Fox, Ruslan Horblyuk, Lynn McRoy, Jack Mardekian, Bhakti Arondekar
Journal: Journal of Clinical Oncology (2016)

561 Background: Endocrine therapy (ET) is recommended as 1st line of therapy (LOT) for patients (pts) with HR+/HER2- mBC. Chemotherapy (CT), however, has also been used, though wide practice variation exists. The purpose of this study was to understand the utilization of 1st line CT and its toxicities for HR+/HER2- mBC in a US community oncology setting. Methods: A retrospective study was conducted using US Oncology’s iKnowMed electronic health record database, supplemented with chart review. Post-menopausal women with a diagnosis of HR+/HER2- mBC between Jan. 2010 and Dec. 2013 who received CT as the 1st therapy within 90 days after diagnosis were included. Pts were followed through Dec. 2014 or their last visit. CT regimens and toxicities were analyzed. Results: Of the 8,953 post-menopausal mBC pts, 39.4% (n = 3,525) received at least one CT agent within 90 days after diagnosis. Among those, 598 pts met all inclusion criteria with a final sample of 150 pts, verified by chart review, for analysis. The majority of pts had recurrent mBC (62.7%). Median age was 63 years (range 41-86). In the 1st line setting, the most common single agent CT regimens were paclitaxel (24.7%), nab-paclitiaxel (15.3%), and capecitabine (14.0%). The most common combination regimens of CT included cyclophosphamide, paclitaxel/nab-paclitaxel, and docetaxel-containing regimens (18.7%, 13.3%, 11.3%, respectively). Median duration of 1st line CT was 3.9 months (range < 1 to 42.4). CT was discontinued in 69.3% of pts, and the main reasons for discontinuation, as noted by physician, were response achieved (38.7%), disease progression (29.3%), and toxicity (19.3%). The most common side effects included fatigue/malaise (87.0%), anemia (43.8%), neuropathy (43.8%), neutropenia/neutropenic fever (43.8%), nausea/vomiting (39.0%), abdominal pain (34.9%), and diarrhea (32.9%). 72.7% of pts received ET after CT. Conclusions: Both single agent and combination CT were frequently used in the 1st line setting for post-menopausal pts with HR+/HER2- mBC. CT toxicities were common and should be considered when planning individualized treatment.
Goserelin plus tamoxifen versus tamoxifen alone in pre-or peri-menopausal patients with hormone receptor-positive early-stage breast cancer: A randomized, controlled clinical trial in China.
Authors: Hongjian Yang, Xingfei Yu, Xiangyun Zong, Daobao Chen, Xiaowen Ding, Yang Yu, Dehong Zou, Xiangming He, Weiliang Feng, Jie Chen, Wenju Mo, Chen Wang
Journal: Journal of Clinical Oncology (2016)

562 Background: In our previous study, goserelin has been reported downregulating the estradiol level, breast density and endometrial thickness in Chinese pre-/peri-menopausal hormone positive (HR+) breast cancer. Here, the prognositic results of this study will be reported: disease-free survival (DFS) and overall survival (OS) of goserelin plus tamoxifen (TAM) versus TAM alone in pre-/peri-menopausal HR+ early-stage breast cancer in China (NCT00827307). Methods: Pre-/peri-menopausal patients with HR+ early-stage breast cancer (after finishing surgery, chemotherapy, radiotherapy if applicable) were randomized to receive either goserelin 3.6mg ih. every 28 days for 1.5 years plus TAM 10 mg po. twice a day for 5 years (Group A) or TAM alone for 5 years (Group B) as adjuvant endocrine therapy. The patients also were classified according to recurrence-risk grade for stratified analysis. The DFS and OS in total patients and in stratified risk grade subgroups were analyzed. Results: From 22 June 2008 to 31 December 2009, 110 eligible patients were recruited. The medium follow-up time is 72 months. Because of 19 cases dropped out, there were 47 patients of group A and 44 patients of group B included in for final analysis. Patients in group A had better DFS and OS than those in group B although not statistically significant due to small sample size (DFS: HR = 0.452, P = 0.261, OS: HR = 0.301, P = 0.299). In high-risk (1~4 LN+ and HER2+/ ≥ 4 LN+) subgroup, there were no patients with recurrent/metastasis (0/10) in group A while three patients with recurrent/metastasis (3/8) in group B, goserelin combined with TAM has better DFS than TAM alone (Log-rank test, χ2= 4.324, P = 0.038). In total patients, COX proportional hazard regression model (forward conditional method) showed that the number of LN+ significantly impacts the DFS (P = 0.011). Meanwhile, both the age and the tumor size have significant impacts on OS (P = 0.028 and P = 0.030, respectively). Conclusions: Goserelin combined with TAM was suggested to improve DFS in HR+ pre-/peri-menopausal breast cancer with high-recurrence risk grade. Clinical trial information: NCT00827307.
Diarrhea prevention and prophylaxis with crofelemer in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and docetaxel or paclitaxel with or without carboplatin.
Authors: Jennifer Gao, Ming Tony Tan, Sandra M. Swain
Journal: Journal of Clinical Oncology (2016)

TPS628 Background: Chemotherapy-induced diarrhea (CID) occurs in 40-80% of breast cancer patients on HER2 directed therapy with THP or TCHP. In the CLEOPATRA trial, 67% of patients who received THP had all grade and 8% had grade 3 diarrhea. In the TRYPHAENA trial, 72% of patients who received neoadjuvant TCHP had all grade and 11.8% had grade 3-4 diarrhea. In a phase 2 trial of trastuzumab and pertuzumab with weekly paclitaxel, 81% of patients had all grade and 3% had grade 3-4 diarrhea. In addition to impacting electrolytes and kidney function, diarrhea can also affect a patient’s quality of life. Studies suggest blocking epidermal growth family receptors such as HER2 can cause excess chloride secretion, causing impaired gut absorption and secretory diarrhea. Crofelemer is an extract from the bark of Croton lechleri. It inhibits luminal chloride efflux by blocking the calcium activated chloride channel and the cystic fibrosis transmembrane regulator, two chloride channels in the colon. We propose a trial of crofelemer versus standard of care to prevent CID in HER2 positive breast cancer patients on THP or TCHP. Methods: This is a 1:1 randomized, stratified, open-label phase II study in breast cancer patients on THP or TCHP. There will be three strata: 1) TCHP with docetaxel, 2) THP with paclitaxel, and 3) THP with docetaxel. The treatment group will receive oral crofelemer 125 mg twice daily during cycles 1-2 of THP or TCHP. The control group will receive standard of care (no prophylaxis). The primary endpoint is the total number of patients with all grade diarrhea for two or more consecutive days that is definitely, probably, or possibly due to THP or TCHP during cycles 1 and 2. All patients will keep a bowel movement diary. With a sample size of 46 patients, the study has 81% power to detect a 40% absolute decrease (from 60% to 20%) in the incidence of all grade diarrhea, with a two sided significance level of 0.10 using Fisher’s exact test. The analysis population is all randomized patients who complete 2 cycles of THP or TCHP. THP = trastuzumab, pertuzumab, docetaxel or paclitaxel TCHP = trastuzumab, pertuzumab, carboplatin, docetaxel or paclitaxel.