tbuckley/cabot-search huggingface dataset:
Efficacy and safety in elderly patient subsets across studies investigating endocrine monotherapy versus combination therapy in patients with HR+/HER2−advanced breast cancer.
Authors: Rachel A. Freedman, Sara M. Tolaney
Journal: Journal of Clinical Oncology (2017)

1045 Background: Combination of endocrine therapy and targeted agents in 1st and 2nd-line therapy prolong progression-free survival (PFS) in patients with hormone receptor–positive (HR+), HER2 − advanced breast cancer (ABC). However, a greater risk of adverse events (AEs) and a greater possibility of drug-drug interaction, associated with combination therapy, present challenges in older patients. Methods: This study reviewed PFS and safety data in age-stratified subsets from Phase II or III clinical trials comparing endocrine monotherapy vs combinations of endocrine or targeted therapy in patients with HR+, HER2−ABC. Results: Among 9 identified studies, combination therapy that included ribociclib, palbociclib, and everolimus significantly reduced risk of disease progression vs monotherapy in older and younger patient subsets (Table). For combination therapy that included ribociclib or palbociclib, frequency of discontinuations due to AEs was similar between the subsets; more frequent discontinuations due to AEs were noted in the ≥70-year subset with everolimus. Conclusions: Combination endocrine therapies involving CDK4/6 or mTOR inhibitors have similar efficacy but vary in tolerability among older and younger patients with HR+, HER2− ABC. [Table: see text]
Abstract DPOC-009: DETECTION OF A CLINICALLY OCCULT OVARIAN CARCINOMA BY NEW DIAGNOSTIC TOOLS – A CASE REPORT
Authors: Elisabeth Maritschnegg, Eva Obermayr, Barbara Holzer, Noreen Gleeson, Florian Heitz, Leon Massuger, Gunda Pristauz Telsnigg, Adam Rosenthal, Fabian Trillsch, Els Van Nieuwenhuysen, Michael Zikan, Paul Speiser, Robert Zeillinger
Journal: Clinical Cancer Research (2017)

Abstract 75% of ovarian cancer (OC) cases are detected at an advanced stage. State–of–the–art diagnostic tools don't show sufficient sensitivity, especially in diagnosing early–stage disease. Still, due to lack in alternatives, these methods are used for monitoring BRCA mutation carriers, who face a high penetrance of OC. A 41–year old BRCA1 mutation carrier decided to undergo risk–reducing bilateral salpingo–oophorectomy (rrBSO), currently the only effective way of reducing the OC risk. The day before surgery, 20ml of peripheral blood were drawn to test for the presence of circulating tumor cells (CTCs) by applying a microfluidic device (Parsortix system) and subsequent qPCR. Furthermore, a lavage of the uterine cavity was performed as previously described. According to state–of–the–art techniques, no signs of cancer were present. However, microscopic malignant lesions at both ovaries and the right diaphragm were observed, and final histopathology revealed FIGO IIIB serous OC. Multiple precursor lesions (STICs) were observed in the fallopian tube. qPCR of preoperative enriched cell fraction indicated the presence of CTCs. Analysis of the lavage sample using TP53 mutation analysis revealed 17% mutant allelic fraction. The same mutation was identified in different STIC and invasive lesions. This case shows that early detection of high–grade serous OC does not necessarily translate into a stage shift, but easier to resect disease. Considering the lag–time between STIC to clinically–overt OC development, both described methods present an opportunity for monitoring high–risk patients to delay rrBSO. Both methods proved to be able to diagnose occult OC, and even carry the potential of detecting STICs. Citation Format: Elisabeth Maritschnegg, Eva Obermayr, Barbara Holzer, Noreen Gleeson, Florian Heitz, Leon Massuger, Gunda Pristauz Telsnigg, Adam Rosenthal, Fabian Trillsch, Els Van Nieuwenhuysen, Michael Zikan, Paul Speiser, Robert Zeillinger. DETECTION OF A CLINICALLY OCCULT OVARIAN CARCINOMA BY NEW DIAGNOSTIC TOOLS – A CASE REPORT [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr DPOC-009.
Association Between Prognosis and Tumor Laterality in Early-Stage Colon Cancer
Authors: Safiya Karim, Kelly Brennan, Sulaiman Nanji, Scott R. Berry, Christopher M. Booth
Journal: JAMA Oncology (2017)

Recent data have suggested that disease biology and outcome of colon cancer may differ between right-sided and left-sided tumors. However, the literature on the prognostic value of tumor laterality is conflicting.
Aids to Pathological Technique
Journal: JAMA (1934)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Neutropenic complications with neo/adjuvant adriamycin and cyclophosphamide in early stage breast cancer patients: A prospective study at the McGill University health center.
Authors: Ramy Saleh, Arielle Elkrief, Elmira Afshar, Laurent Azoulay, Sarkis H. Meterissian, Nathaniel Bouganim
Journal: Journal of Clinical Oncology (2017)

e12127 Background: We prospectively investigated the incidence of neutropenic complications (NC) with neo/adjuvant AC (doxorubicin and cyclophosphamide) chemotherapy (CTX) among early-stage breast cancer (ESBC) patients. NC was defined as febrile neutropenia (FN), dose delay/reduction or need of granulocyte colony-stimulating factors (G-CSF) to proceed with CTX. Methods: This was a single-center, observational, prospective cohort study conducted at the McGill University Health Center. All ESBC patients who received AC regimen as neo/adjuvant CTX between February 2016 and February 2017 were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of predictors of NC were estimated using Cox-proportional hazards models. Results: A total of 118 patients, corresponding to 409 cycles of AC were analyzed. Most patients underwent Q3week cycles (83.1%). Median age was 52 years old (IQR 43-61). Prophylactic G-CSF was given to 20 dose-dense patients and 10 Q3weeks patients. In patients not receiving prophylactic G-CSF, 57 (65.5%) manifested at least one episode of NC (corresponding to an incidence rate of 26.4%/cycle of CTX [95% CI: 20.0%-34.2%]), of which 9 developed FN requiring hospital admission. In the final prediction model, body mass index &lt; 25 kg/m 2 (HR: 2.36, 95% CI: 1.16-4.78) and increasing glucose levels (HR: 1.56, 95% CI: 1.14-2.14) were significantly associated with NC. Baseline absolute neutrophil count (ANC) was protective. Conclusions: The incidence of NC in our prospective study is significantly higher than previously reported in retrospective studies (26.4% vs. 12%). Normal BMI and high glucose were associated with the highest risk of NC. More importantly, 65% of ESBC on AC will require G-CSF during their treatment due to a NC episode. [Table: see text]
Abstract 114: Allogeneic Cardiosphere-Derived Cells Are Safe and Effective in a Pig Model of Myocardial Infarction
Authors: Rachel R Smith, Michelle Kreke, Konstantinos Malliaras, Hideaki Kanazawa, Christene A Huang, Ileana Valle, Agnieszka Blusztajn, Kristine Yee, David H Sachs, John Terrovitis, Linda Marban
Journal: Circulation Research (2012)

Allogeneic cardiosphere-derived cells (CDCs) have proven safe and effective in a small animal model of myocardial infarction (MI), and have been shown to act primarily via paracrine mechanisms to stimulate endogenous regeneration. The present translational study tested allogeneic CDCs in a large animal model (mini-pigs). To establish a robust allogeneic model, all pigs were swine leukocyte antigen (SLA) typed by PCR. A male donor and female recipients with full SLA I, II mismatch were used. Pigs underwent balloon occlusion of the LAD for 2.5 hours, followed by reperfusion. Two weeks later, 12.5 million CDCs (n=8) or vehicle (n=6) were infused. Animals were sacrificed 2 weeks or 2 months post-infusion to assess the cellular (histology using a clinical rejection scale) and humoral (donor-specific antibodies, complement-dependent cytotoxicity) immune responses, as well as cardiac function (left ventriculography, hemodynamics, morphometry). Numerous in-life assessments for safety were performed and CDC engraftment was assessed by FISH for Y chromosome. All immunological assays indicated an undetectable response to CDCs. Cardiac enzymes and systemic inflammation showed no differences between groups. There were no systemic histological findings related to CDCs. CDCs did not permanently engraft, with &lt;0.1% persisting 2 weeks post-infusion and none evident 2 months post. Despite evanescent engraftment, functional benefits were seen following infusion of CDCs. Ejection fraction (EF) and infarct size (IS) were significantly improved in CDC-treated animals compared to vehicle-treated 2 weeks post-infusion (EF: 48.6±2.1% vs 38.2±2.6%, p&lt;0.05; IS: 9±2 vs 14±2%, p&lt;0.05). At 2 months, EF still trended higher in CDC-treated animals (42±5 vs 32±10%, p=0.09), and IS still trended lower (14±4 vs 16±7%, p=0.60). Pressure-volume relationships revealed a trend for enhanced contractility in CDC-treated animals (Emax: 3.2±2.2 vs 1.0±1.1 mmHg/mL, p=0.26). The magnitude of the functional benefits was similar to that seen in a prior pig study using autologous CDCs. Overall, results of the present study demonstrate that allogeneic CDCs are largely equivalent to autologous in terms of efficacy, and elicit no detectable immunological response or safety concern.
Confusion Regarding Surgical Delirium—Is Dexmedetomidine the Answer?
Authors: Julia R. Berian, Ronnie A. Rosenthal, Thomas N. Robinson
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
BRAF: An emerging target for triple-negative breast cancer.
Authors: Joan Albanell, Julia Andrea Elvin, Siraj Mahamed Ali, Alexa Betzig Schrock, Jon Chung, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Eric Allan Severson, Sugganth Daniel, Vincent A. Miller, Philip J. Stephens, Laurie M. Gay, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2017)

1099 Background: A series of reports demonstrating the successful use of BRAF and MEK inhibitors in clinically advanced non-melanoma cancers has recently emerged. BRAF alterations in metastatic breast cancer (mBC) are rare and BRAF is not currently considered a target for the disease. Methods: DNA was extracted from 40 microns of FFPE sections from a series of 10,428 cases of metastatic breast cancer (mBC). Comprehensive genomic profiling (CGP) was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of &gt; 550X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Results: 135 (1.2%) of the mBC featured alterations in BRAF. The median age of the 135 female patients was 66 years (range 27 to 83 years). The primary tumor was used for CGP in 50 (37%) and from metastatic sites including lymph nodes, liver, bone, lung, brain, adrenal and soft tissue in 85 (67%). Using CDH1 mutation as the definition of lobular mBC, 126 (93%) were ductal and 9 (7%) were lobular histology. Activating BRAF alterations included amplifications (48%), SV mutations (39%) and rearrangements (13%). No (0%) mBC had multiple BRAF GA in the same case. 34% of BRAF SV were V600E and 66% were a wide variety of non-V600E GA. 10 (7.4%) of 135 BRAF mutated mBC featured ERBB2 amplification with 1 (1%) having an ERBB2 SV mutation and 1 (1%) having both ERBB2 amplification and SV GA. Of the 115 BRAF GA cases with known hormone receptor status 71 (62%) were ER negative, 44 (38%) were ER positive and 63 (55%) were triple negative (TNBC). Other targetable genes enriched in mBC with BRAF GA included CDK6 (p = 0.001), HGF (p &lt; 0.001) and MET(p &lt; 0.001). The median TMB was 4.5 with 17 (13%) of cases with TMB &gt; 10 mut/Mb and 7 (5%) of cases with &gt; 20 mut/Mb. Conclusions: BRAF alterations, although uncommon in mBC representing only 1.2% of cases, are enriched in TNBC and feature both targetable base substitutions and rare fusions. BRAF GA may be a rare cause of anti-HER2 therapy resistance in a subset of ERBB2 driven mBC. Targetable genes co-altered with BRAF in mBC include CDK6, HGF and MET. The TMB in BRAF altered mBC is significantly higher than that for mBC in general and indicates potential role for immunotherapy for these patients.
TBCRC 036: Window of opportunity clinical trial reveals adaptive kinome reprogramming in single and combination HER2-targeting in breast cancer (BrCa).
Authors: Steven P Angus, Timothy Stuhlmiller, Noah Sciaky, Xin Chen, Rashid Naim, Maki Tanioka, Kristalyn K. Gallagher, Andres Forero, Ian E. Krop, Alastair Mark Thompson, Rashmi Krishna Murthy, Xiaping He, Charles M. Perou, Shelton Earp, Lisa A. Carey, Gary L. Johnson
Journal: Journal of Clinical Oncology (2017)

1027 Background: HER2 targeting is challenging due to heterogeneity in response and resistance. Adaptive kinome reprogramming (AKRP) is a resistance mechanism to kinase-targeted therapy (Rx) in TNBC ( Cancer Discovery2017). We studied AKRP in HER2+ BrCa by comparing transcriptome and kinome profiles before and after Rx with FDA-approved anti-HER2 drugs and combinations: trastuzumab (T), pertuzumab (P), T+P, or T+ lapatinib (T+L). Profiling was by RNA sequencing (RNAseq) and multiplexed inhibitor beads coupled with mass spectrometry (MIB/MS). MIB affinity-purification selectively enriches the functional kinome ( &gt; 250 kinases per sample) for identification/quantification by MS. Methods: Eligible patients (pts) had biopsy then randomization to: T (8 mg/kg iv), P (840 mg iv), T+P (same doses), or T+L (8mg/kg iv x1, 1000 mg po/d) 7 days before breast surgery. RNAseq and MIB/MS on paired pre- and post-Rx samples were analyzed using DESeq2 (comparison of mean difference in log 2 fold change (post/pre)) and MaxQuant (kinome response profiling) software. Results: Of 23 evaluable pts, we obtained informative paired RNAseq data in 13 (5 T, 3 P, 3 T+P, 2 T+L), and identified distinct expression responses (p adj ≤0.05) between Rx arms, such as FGFR4 increase in P vs T or T+P. All samples had HER2 enrichment by RNAseq. Kinome response profiling from 11 pts (3 T, 3 P, 4 T+P, 2 T+L) revealed consistent increases in MIB binding (abundance a/o activity) of several tyrosine kinases regardless of Rx, including immune-related kinases SYK, IRAK4, FGR, and FES. Other kinases, such as p90Rsk and GSK3B, exhibited increased binding in response to T and T+P, but not P alone. While not quantifiable in every sample due to detection limits, HER2 inhibition was observed by loss of MIB binding in select post-Rx versus pre-Rx comparisons. Conclusions: HER2 inhibition upregulates and activates specific receptor tyrosine kinases in tumor cells as well as alterations that may reflect changes in the immune compartment. HER2+ BrCa exhibit plasticity, characterized by distinct expression and kinome profile changes within 1 week of initiating Rx, and reprogramming in both immune responses and BrCa cells. Clinical trial information: NCT01875666.
Response to: M.F. Holick ‘Can you have your cake and eat it too? The sunlight D-lema’
Authors: D.C. Whiteman, C.M. Olsen, A.C. Green
Journal: British Journal of Dermatology (2017)

We read with interest the recent paper by Felton and colleagues (1) describing the effects of solar-simulated ultraviolet radiation (UVR) on cutaneous DNA damage and vitamin D production. However, we were disappointed by the accompanying editorial by Dr Holick (2) proclaiming that healthcare regulators (and by inference, doctors and the public) “could have their cake and eat it too”. In particular, his assertion that “sensible sun exposure that does not cause burning” should raise “little concern” about skin cancer risk is at odds with the photodamage observed by Felton and colleagues in the epidermal cells of fair-skinned participants following repeated, low-level sun exposure.

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The Enigma of Regional Lymph Nodes in Melanoma
Authors: Daniel Coit
Journal: New England Journal of Medicine (2017)

Because of an incomplete understanding of regional lymph nodes, they have been characterized either as active filters or barriers to the distant spread of disease1 or as passive indicators of the risk of distant spread.2 The truth almost certainly resides in a hybrid model that embraces aspects of both theories. This lack of understanding has frequently led to a "more is better" philosophy in the surgical management of regional lymph nodes. Yet in melanoma, as in so many other cancers, the elective removal of clinically negative nodes has rarely, if ever, been shown to increase disease-specific survival.The findings of . . .
Human CYP2A13 and CYP2F1 Mediate Naphthalene Toxicity in the Lung and Nasal Mucosa of CYP2A13/2F1-Humanized Mice
Authors: Lei Li, Sarah Carratt, Matthew Hartog, Nataliia Kovalchuk, Kunzhi Jia, Yanan Wang, Qing-Yu Zhang, Patricia Edwards, Laura Van Winkle, Xinxin Ding
Journal: Environmental Health Perspectives (2017)

The potential carcinogenicity of naphthalene (NA), a ubiquitous environmental pollutant, in human respiratory tract is a subject of intense debate. Chief among the uncertainties in risk assessment for NA is whether human lung CYP2A13 and CYP2F1 can mediate NA's respiratory tract toxicity.We aimed to assess the in vivo function of CYP2A13 and CYP2F1 in NA bioactivation and NA-induced respiratory tract toxicity in mouse models.Rates of microsomal NA bioactivation and the effects of an anti-CYP2A antibody were determined for lung and nasal olfactory mucosa (OM) from Cyp2abfgs-null, CYP2A13-humanized, and CYP2A13/2F1-humanized mice. The extent of NA respiratory toxicity was compared among wild-type, Cyp2abfgs-null, and CYP2A13/2F1-humanized mice following inhalation exposure at an occupationally relevant dose (10 ppm for 4 hr).In vitro studies indicated that the NA bioactivation activities in OM and lung of the CYP2A13/2F1-humanized mice were primarily contributed by, respectively, CYP2A13 and CYP2F1. CYP2A13/2F1-humanized mice showed greater sensitivity to NA than Cyp2abfgs-null mice, with greater depletion of nonprotein sulfhydryl and occurrence of cytotoxicity (observable by routine histology) in the OM, at 2 or 20 hr after termination of NA exposure, in humanized mice. Focal, rather than gross, lung toxicity was observed in Cyp2abfgs-null and CYP2A13/2F1-humanized mice; however, the extent of NA-induced lung injury (shown as volume fraction of damaged cells) was significantly greater in the terminal bronchioles of CYP2A13/2F1-humanized mice than in Cyp2abfgs-null mice.CYP2F1 is an active enzyme. Both CYP2A13 and CYP2F1 are active toward NA in the CYP2A13/2F1-humanized mice, where they play significant roles in NA-induced respiratory tract toxicity. https://doi.org/10.1289/EHP844.
A propensity score analysis exploring the impact of adjuvant chemotherapy (aCT) in a multi-center series of resected early stage pure invasive lobular breast carcinoma (ILC).
Authors: Luisa Carbognin, Isabella Sperduti, Grazia Arpino, Maria Vittoria Dieci, Francesco Schettini, Gaia Griguolo, Valentina Guarneri, Matteo Brunelli, Rolando Nortilli, Elena Fiorio, Veronica Parolin, Sara Pilotto, Enrico Orvieto, Erminia Manfrin, Francesca Pellini, Giovanni Paolo Pollini, Pier Franco Conte, Sabino De Placido, Giampaolo Tortora, Emilio Bria
Journal: Journal of Clinical Oncology (2017)

539 Background: Patients (pts) resected for early breast cancer are assigned to receive aCT according to international guidelines based upon immunophenotype and clinical/pathological features, regardless of the histotype, given the lack of prospective data for ILC. Thus, the magnitude of the benefit of aCT for ILC is still not sizable. The aim of this analysis was to investigate the effect of aCT in a multi-center series of early stage pure ILC. Methods: Clinical-pathological data of consecutive pts affected by pure ILC, undergone surgery at 3 Italian institutes, were correlated with disease-free and overall survival (DFS/OS) using a Cox model. A propensity score analysis was performed to evaluate the prognostic impact of aCT. Kaplan-Meier curves were compared with Log-Rank analysis. Results: Data from 739 pts were gathered (median age 57 years (yrs); Luminal/Triple-Negative/HER2 pos.: 98%/1.6%/0.4%). At median follow-up of 78 months, 5-/10-yrs DFS and OS were 79.4%/66.0% and 91.4%/76.5%, respectively. Tumor-size according to TNM (T, HR 1.34, 95% CI 1.04-1.72, p=0.025) and lymph-node (N) status (HR 2.39, 95% CI 1.47-3.89, p&lt;0.0001) were independent predictors for DFS at multivariate analysis. T (HR 1.87, 95% CI 0.99-3.54, p=0.05), N status (HR 3.24, 95% CI 1.69-6.22, p&lt;0.0001), Ki67 (HR 2.48, 95% CI 0.95-6.42, p=0.06), and age (HR 2.23, 95% CI 1.16-4.30, p=0.016) were predictors for OS. A significant prognostic effect of aCT upon OS was found after adjusting for independent factors with the propensity score method, as shown in the table below. Particularly, aCT significantly prolongs OS and DFS in pts with T &gt;1, with an absolute difference of 17%/35% and 15%/13% at 5 and 10 yrs, respectively ( p=0.003 and p=0.04). OS was longer for pts with positive N ( p=0.02), Ki67 &gt;4% ( p=0.01) and grading &gt;1 ( p=0.01). Conclusions: Despite the retrospective nature of this analysis, the propensity score analysis indicates that pts with ILC may significantly benefit from aCT in terms of long-term survival, particularly for larger and more aggressive tumors. [Table: see text]