tbuckley/cabot-search huggingface dataset:
Impact of obesity in postmenopausal early breast cancer patients receiving frontline adjuvant aromatase inhibitors.
Authors: Ugur Sahin, Ibrahim Petekkaya, Cagatay Arslan, Saim Furkan Sarici, Mustafa Solak, Özge Keskin, Yavuz Yasin Ozisik, Kadri Altundag
Journal: Journal of Clinical Oncology (2012)

e11020 Background: Aromatase inhibitors (AIs), anastrozole (ANA) and letrozole (LET), have been shown to be more effective than tamoxifen in the adjuvant treatment of postmenopausal hormone receptor positive breast cancer. However, data from preclinical studies and subgroup analyses of some major clinical trials suggest differring efficacy among AIs. Yet the best clinical choice is still not very clear. This retrospective study aims at comparing the results of treatment with either AI among different subgroups of patients, especially among the obese patients. Methods: Between 2006-2011, 335 women with stage I to IIIC hormone receptor positive postmenopausal breast cancer treated with either ANA or LET as adjuvant treatment were included. Body mass index (BMI), estrogen and progesterone receptor (ER and PR) and HER-2 status at the time of diagnosis were recorded. Patients were grouped as BMI ≤ 30 and BMI &gt; 30. The Kaplan-Meier survival estimates were calculated. Subgroups were compared with the log rank test. A 5 % type-I error was used to infer statistical significance. Results: The percentage of patients receiving ANA or LET were 47.2% and 57.8%, respectively. Median age at diagnosis was 58 (42-84) and lower in the ANA group (p=0.04). Stage II to IIIC disease was present in 76.8 % and the distribution was similar between ANA and LET (p=0.84). Median time of follow-up was 29 months (6-124) and median duration of hormonotherapy was 29 months (3-68) and similar between two groups (p=0.52 and p=0.55, respectively). Of the patients 41.2 % had a BMI of &gt; 30. There was no significant difference in overall (OS) and progression-free (PFS) survivals between ANA and LET (p=0.08 and p=0.94, respectively). However, among patients with a BMI of &gt; 30 a statistically insignificant benefit in PFS was observed with LET (p=0.1). ER, PR and HER2 status had no significant impact on OS and PFS. Conclusions: In a median follow-up of 29 months letrozole and anastrozole yielded similar OS and PFS. However, among patients with a BMI of &gt; 30, LET might bring about a PFS advantage. In selected obese patients LET might be a reasonable choice in this setting. Larger studies with long term follow-up are needed to reach an exact conclusion.
A monocentric retrospective analysis of TILs and AR as hints for prognosis definition in TNBC.
Authors: Agnese Losurdo, Rita De Sanctis, Bethania Fernandes, Valentina Errico, Andrea Sagona, Giovanna Masci, Monica Zuradelli, Elisa Agostinetto, Rosalba Torrisi, Wolfgang Gatzemeier, Alberto Testori, Massimo Roncalli, Marco Alloisio, Corrado Tinterri, Armando Santoro
Journal: Journal of Clinical Oncology (2018)

e12580 Background: TILs have been proposed as a prognostic biomarker in many tumor types both in the adjuvant and neoadjuvant setting. In TNBC, TILs are present at the highest level and have been demonstrated to be associated with better prognosis. TNBC is a highly diverse group of cancers and subtyping is necessary to better identify patient-tailored therapies. Cluster analysis by gene expression identified 6 TNBC subtypes (2 basal-like, 1 immunomodulatory, 1 mesenchymal, 1 mesenchymal stem-like and 1 luminal androgen receptor) to be informative for patients' tailored therapy selection. Methods: We retrospectively collected 160 early stage TNBC consecutively treated at our Institution from 2006 to 2015. Data were obtained for clinico-pathological patients' characteristics. On IHC archive slides we analyzed stromal TILs scored as a continuous variable and androgen receptor's (AR) percentage and intensity of expression. We performed Cox analyses for DFS and for OS, and we used chi-square and Fisher test to evaluate the correlation between TILs, AR and other clinical variables. To define high vs low TILs, an internal dataset cut-off of 10% was considered. Results: 150 patients were eligible for IHC analyses of TILs and AR. With a median follow-up of 6.5 years, 41 local and/or distant relapse events were observed and 28 patients died of disease. Interestingly, TILs were found to be significantly associated with nodal status (N0 vs N1-3), grading (G2 vs G3) and Ki-67 (<20% vs ≥ 20%) (p=0.007, p=0.055 and p=0.002, respectively). AR was also significantly associated with proliferation, specifically AR-positive cases presented mostly with a Ki-67<20% (p=0.008). Probably due to the paucity of events, no statistically significant association of TILs and AR with either DFS or OS was observed. Conclusions: TILs are a promising prognostic marker, but still prospective validation is needed to integrate them into clinical practice. Among TNBC, the identification of AR-expressing luminal subtype might provide a targeted therapy chance for a low proliferation TNBC subtype. Larger prospective trials are likely to validate TILs prognostic role and to explore the universe of TNBC subtypes targeted therapies opportunities.
Selection for Oncotype Dx testing among young women with early-stage ER+/HER2- breast cancer.
Authors: Philip Daniel Poorvu, Shari I. Gelber, Shoshana M. Rosenberg, Kathryn Jean Ruddy, Rulla Tamimi, Jeffrey M. Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Laura C. Collins, Ellen Warner, Ann H. Partridge
Journal: Journal of Clinical Oncology (2018)

533 Background: The Oncotype Dx Recurrence Score (RS) predicts distant recurrence risk and benefit from chemotherapy for women with early-stage estrogen receptor (ER) positive (+)/human epidermal growth factor receptor 2 (HER2) negative (-) breast cancer (BC). Due to the independent risk of young age and small proportion of young women in the validation studies, providers may be hesitant to rely on the RS among young women. Methods: Using a multi-center, prospective cohort study of women newly diagnosed with BC at age ≤40 years enrolled from 2006-2016, we identified participants with stage I-III, ER+/HER2- BC. Clinical data were obtained through patient surveys and medical record review. Factors associated with RS testing by univariable analyses (p < 0.20) were used to generate a multivariable logistic regression model. Results: 182 (32%) of 575 eligible women had a RS performed (Table 1). Younger women (ORage ≤30 vs 36-40= 0.49, p = 0.03) and those with larger (OR> 2cm vs ≤2cm= 0.54, p = 0.007), node positive (ORpos vs neg= 0.14, p < 0.0001) or high grade tumors (ORhigh vs low/intermediate= 0.37, p < 0.0001) were less likely to have a RS performed. Of women who had a RS performed, chemotherapy usage was 21/88 (24%), 44/77 (57%), and 17/17 (100%) among those with low, intermediate, and high RS, respectively. Most women with low risk RS who received chemotherapy had other low risk features: 67% T1, 67% N0, and 86% low/intermediate grade. Conclusions: Despite the development of multigene testing to assess the benefit of chemotherapy, many young women with node-negative ER+/HER2- BC are not tested, and when tested, a substantial percentage receive chemotherapy despite a low RS. This highlights an opportunity to improve individualized care for young women with BC. Recurrence score testing. RS/N (%) OR (95% CI) p-value Age ≤30 18/75 (24) 0.49 (0.26,0.93) 0.03 31-35 48/158 (30) 0.87 (0.55,1.34) 0.57 36-40 116/342 (34) Ref Tumor size ≤ 2cm 137/326 (42) Ref > 2cm 45/249 (18) 0.54 (0.35,0.85) 0.007 Nodal status N0 154/322 (48) Ref N+ 25/249 (10) 0.14 (0.09,0.24) < 0.0001 Grade Low/Intermediate 146/357 (41) Ref High 35/213 (16) 0.37 (0.24,0.59) < 0.0001 * Missing data and factors not associated with RS testing not included
Pharmacokinetics of CT-P6 and reference trastuzumab by clinical factors in patients with HER2 positive early-stage breast cancer (EBC).
Authors: Justin Stebbing, SunYoung Yu, MinJi Kim, Sijin Park, SinHye Kim, HyunAh Kim, NaHyun Kim, Francisco J. Esteva
Journal: Journal of Clinical Oncology (2018)

591 Background: CT-P6 is a proposed biosimilar to reference trastuzumab, Herceptin (H) (Genentech, S San Francisco, CA, USA). A randomized phase III trial showed efficacy equivalence and comparable pharmacokinetics (PK) and safety between CT-P6 and H (NCT02162667). Clinical factors have been shown to affect trastuzumab parameters. We compared known factors that may affect the PK of CT-P6 and H in HER2 positive EBC patients. Methods: A total of 549 patients were randomized to receive CT-P6 (n = 271) or H (n = 278) with combination chemotherapy in the neoadjuvant setting. CT-P6 or H was administered at 8 mg/kg (Cycle 1 only) followed by 6mg/kg every 3 weeks. The primary endpoint was pathological complete response (pCR). Key PK parameters for CT-P6 and H were assessed during the neoadjuvant period in terms of Ctrough and Cmax. Ctrough at steady state (predose of cycle 8, CtroughSS) was analyzed by age, race, weight, and pathological response. Results: The serum concentration gradually increased and steady state was reached at cycle 7 (predose of cycle 8). There was no statistically significant difference between CT-P6 and H in any of the subgroups analyzed. Clinical trial information: NCT02162667. Conclusions: The serum CtroughSS level of trastuzumab was comparable between CT-P6 and H groups in all subgroups analyzed. These data support the PK similarity between CT-P6 and H independently of age, race, weight or pCR assessment method. Statistical analysis of geometric mean CtroughSS (μg/ml) for trastuzumab (ANOVA) by subgroup. Subgroup CT-P6 H Ratio of Geometric Means (95% CI) Age < 65 54.33 55.35 98.16 (90.86,106.05) ≥65 58.72 59.36 98.92 (81.44,120.15) Race Asian 47.28 48.39 97.70 (79.87,119.51) Non-Asian 56.79 57.55 98.67 (91.58,106.31) Weight < 70kg 52.70 51.28 102.78 (92.67,114.00) ≥70kg 57.41 60.92 94.25 (85.58,103.80) Total Pathological Response (breast and lymph nodes) pCR (ypT0/is ypN0) 54.30 57.57 94.32 (85.45,104.11) No pCR 55.23 54.33 101.66 (91.64,112.76) Breast Pathological Response pCR (ypT0/is) 55.00 56.40 97.51 (88.57,107.36) No pCR 54.63 55.31 98.76 (88.64,110.03) Breast Pathological Response (GBG criteria) pCR (ypT0 ypN0) 54.52 58.58 93.08 (83.35,103.95) No pCR 54.99 54.16 101.53 (92.40,111.56)
Nur77 protects against adverse cardiac remodelling by limiting neuropeptide Y signalling in the sympathoadrenal-cardiac axis
Authors: Lejla Medzikovic, Cindy van Roomen, Antonius Baartscheer, Pieter B van Loenen, Judith de Vos, Erik N T P Bakker, Duco S Koenis, Amin Damanafshan, Esther E Creemers, E Karin Arkenbout, Carlie J M de Vries, Vivian de Waard
Journal: Cardiovascular Research (2018)

Cardiac remodelling and heart failure are promoted by persistent sympathetic activity. We recently reported that nuclear receptor Nur77 may protect against sympathetic agonist-induced cardiac remodelling in mice. The sympathetic co-transmitter neuropeptide Y (NPY) is co-released with catecholamines and is a known cardiac modulator and predictor of heart failure mortality. Recently, transcriptome analyses revealed NPY as a putative target of Nur77. In this study, we assess whether Nur77 modulates adverse cardiac remodelling via NPY signalling. Nur77 represses NPY expression in the PC12 adrenal chromaffin cell line. Accordingly, NPY levels are higher in adrenal gland, plasma, and heart from Nur77-KO compared to wild-type mice. Conditioned medium from Nur77-silenced chromaffin cells and serum from Nur77-KO mice induce marked hypertrophy in cultured neonatal rat cardiomyocytes, which is inhibited by the NPY type 1 receptor (NPY1R) antagonist BIBO3304. In cardiomyocytes from Nur77-KO mice, intracellular Ca2+ is increased partially via the NPY1R. This is independent from elevated circulating NPY since cardiomyocyte-specific Nur77-deficient mice (CM-KO) do not have elevated circulating NPY, but do exhibit BIBO3304-sensitive, increased cardiomyocyte intracellular Ca2+. In vivo, this translates to NPY1R antagonism attenuating cardiac calcineurin activity and isoproterenol-induced cardiomyocyte hypertrophy and fibrosis in full-body Nur77-KO mice, but not in CM-KO mice. The cardioprotective action of Nur77 can be ascribed to both inhibition of circulating NPY levels and to cardiomyocyte-specific modulation of NPY-NPY1R signalling. These results reveal the underlying mechanism of Nur77 as a promising modifier gene in heart failure.
Regenerative Peripheral Nerve Interface for Management of Postamputation Neuroma
Authors: Carrie A. Kubiak, Stephen W. P. Kemp, Paul S. Cederna
Journal: JAMA Surgery (2018)

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Increasing physical activity in cancer survivors at cardiovascular risk using Fitbits: Randomized controlled trial.
Authors: Chloe Marie Maxwell-Smith, Paul Andrew Cohen, Cameron Platell, Patrick Tan, Jason Tan, Paul Salama, Michael Levitt, Gregory Bryan Makin, Stuart Salfinger, Ganendra Raj Kader Ali Mohan, Robert Kane, Dana Hince, Sarah Jane Hardcastle
Journal: Journal of Clinical Oncology (2018)

93 Background: Efforts to increase physical activity in cancer survivors have typically been facility-based, and results have generally not been durable. Home-based interventions provide a more feasible option, and are likely to produce longer-lasting benefits. Wearable trackers present a novel opportunity for monitoring physical activity in a practical way. The Health Action Process Approach model suggests that strategies such as action-planning and overcoming barriers may be effective for transitioning individuals from intention to behavioural change. This trial aims to increase physical activity in cancer survivors at cardiovascular risk, by implementing a 24-week self-monitoring and action-planning intervention using Fitbits. Methods: Sixty-eight cancer survivors were recruited to participate in the trial. Eligibility criteria included: insufficiently physically active, presence of cardiovascular risk factors, and completion of active cancer treatment in the five years prior to recruitment. Trial assessments are performed at baseline, 12-weeks, and 24-weeks, and measure physical activity (using 7-day accelerometer data), BMI, blood pressure, physical activity attitudes, barriers and perceived outcomes. Participants were randomly allocated to treatment and control groups, following the baseline assessment. Each participant in the treatment group was given a Fitbit Alta to monitor activity for the 24-week trial, attended two 2-hour group sessions involving goal-setting and action-planning activities, and a follow-up phone call to ensure program adherence. Results: Data collection is currently underway. Data analysis will use the Group x Time interaction from a General Linear Mixed Model analysis. Conclusions: As the population of cancer survivors is largely inactive and at cardiovascular risk, interventions are warranted. Specifically, physical activity interventions that are feasible, have robust theoretical underpinnings, and suit the preferences of cancer survivors post-treatment, show promise as a long-term solution. Clinical trial information: 2617000131358.
Correlation of pathologic and radiologic complete response in the axilla after neoadjuvant chemotherapy for breast cancer.
Authors: Jessica Charlotte Gooch, Timothy Borjas, Jennifer Chun Kim, Alexis Yakes, Talia Jubas, Deborah M. Axelrod, Amber Guth, Karen Hiotis, Richard L. Shapiro, Linda Moy, Freya Ruth Schnabel
Journal: Journal of Clinical Oncology (2018)

e12611 Background: Accurate assessment of response to neoadjuvant chemotherapy (NAC) is important for surgical planning, particularly in management of the axilla. We evaluated the correlation between radiologic complete response (rCR) in the axilla on MRI and likelihood of pCR at the time of surgery. Methods: Our institutional database was queried for patients who underwent NAC from 2010-2016 and had pre- and post-NAC MRI images or report available for review. Clinicopathologic characteristics and MRI findings were recorded. Descriptive statistics were performed. Results: Of 62 patients identified, 54 (87.1%) had suspicious or positive nodes on pretreatment MRI. Among 45 patients with a pretreatment axillary biopsy, 38 (61.3%) had positive nodes. After treatment, rCR was seen in 24.2% and pCR was found in 32.3%. The positive predictive value (PPV) of rCR on MRI was 53%, while negative predictive value was 74%. Patients with resolved axillary nodal disease by MRI had a 37.5% chance of having positive nodes at the time of surgery (Table). Conclusions: MRI had a PPV of only 53% for a complete response in the axilla.Even in the presence of rCR, surgeons must have a high level of suspicion for residual nodal disease after NAC.MRI findings are insufficient to determine extent of axillary surgery after NAC. Variable Outcome (n = 62) Pretreatment MRI Negative nodes 8 (12.9%) Positive (enlarged/suspicious/abnormal) nodes 54 (87.1%) Pretreatment Axillary Biopsy None 17 (27.4%) Negative 7 (11.3%) Positive 38 (61.3%) Final Pathology Stage No residual carcinoma 20 (32.3%) 0 6 (9.7%) I 10 (16.1%) II 14 (22.6%) III 9 (14.5%) IV 3 (4.8%) Axillary surgery SLNB 13 (21%) Completion ALND 17 (25.8%) ALND 29 (46.8%) None 4 (6.4%) Radiologic complete response (rCR) 15 (24.2%) Pathologic complete response (pCR) 20 (32.3%) pCR No pCR Breast and axilla imaging findings rCR 8 (53%)* 7 (46.7%) No rCR 12 (25%) 35 (74%)** Pathologic Negative Axillary Nodes Pathologic Positive Axillary Nodes Radiologic Nodal Burden Stable or None 6 (17.6%) 3 (12.5%) Decreased 13 (38.2%) 12 (50%) Resolved 15 (44.1%) 9 (37.5%) * PPV; ** NPV
Enhancing provider engagement and accountability: A strategy for survivorship care plan implementation within a large hospital network.
Authors: Natalie Garces, Tara Eaton, Daisuke Goto
Journal: Journal of Clinical Oncology (2018)

56 Background: Challenges to Survivorship Care Plan (SCP) implementation persist and guidelines to facilitate provider engagement and accountability are needed. In 2014, Levine Cancer Institute (LCI), part of one of the largest Commission on Cancer (COC) hospital networks, instituted a SCP delivery model. The patient’s LCI or LCI-affiliated physician or advanced care provider (ACP) is responsible to create and deliver the SCP. This presentation updates and extends prior work presented at the 2017 ASCO Cancer Survivorship Symposium to demonstrate the utility of enhanced provider engagement and accountability in SCP program expansion at LCI. Methods: The Survivorship Section partnered with the Cancer Committee to develop a system to enhance provider engagement and accountability. Strategies to improve engagement included: emailed SCP metrics (monthly goals and volume reports) and poster presentations to demonstrate SCP value to Tumor Site Section Leaders (TSSLs), administrators and providers. Strategies to promote accountability included: (1) partnered with TSSLs to clarify SCP eligibility criteria, set monthly goals and identify methods to optimize delivery; (2) discussed SCP metrics within each TSSL to highlight participation rates of providers or clinics; (3) presented Section- and clinic-specific SCP performance at quarterly Cancer Committee, National Accreditation Program for Breast Cancer leadership and Operational meetings; and (4) required all newly hired outpatient ACPs to receive SCP training and included SCP delivery in yearly ACP goals. Results: Since 2014, the total number of SCPs, participating providers, clinics and cancer types has grown 25-, 17-, 7- and 22-fold, respectively. Conclusions: LCI developed a multilayer partnership strategy that enhanced engagement and accountability at the leadership and provider level. This partnership significantly increased numbers of SCPs delivered over four years and allowed us to meet COC goals. [Table: see text]
The impact of a well breast cancer patient transition model of care on oncologists’ practice.
Authors: Seungree Nam, Julie Gilbert, Jonathan Sussman, Leta Forbes, Victoria Zwicker, Paula Doering, Hasmik Beglaryan
Journal: Journal of Clinical Oncology (2018)

39 Background: The transitioning of well breast cancer patients, post-treatment, to family physicians is accepted as a safe and effective model of care. Numerous studies have focused on patients’ experience and health outcomes, but research has not examined the experience of oncologists who are practicing in this model of care. The purpose of this research is to explore the impact of a transition model of care on oncologists’ practice. Methods: Purposive sampling was employed to recruit and interview oncologists who have been transitioning patients to family physicians for two or more years. A total of 15 medical and radiation oncologists practicing in Ontario, Canada were interviewed. Data were analyzed using thematic analysis. Results: Most oncologists interviewed were confident that the transitioning of patients to family physicians is safe for many patients post-treatment. Despite some concerns about the feasibility of the model, namely acceptance of the model among patients and family physicians, oncologists perceived that the model enhances efficiency and sustainability of the cancer system. As the volume of patients in follow-up decreased, oncologists saw a variety of impacts including: a reduction in overbooking in their clinics; more new patients able to be seen in consultation each week; more flexibility in their schedules to accept urgent appointments; and an increased ability to spend more time with patients who are dealing with complex issues. For some oncologists, well patient appointments are a rewarding part of their work. Meanwhile, many experience challenges with increased intensity of workload. Oncologists recognize that some patients and family physicians may be reluctant but they believe that early communication with patients about eventual transition, and improved communication with family physicians can enhance the acceptability of this model of care. Conclusions: Oncologists interviewed in this study reported that the time they used to spend with well follow-up patients can now be spent on other activities that contribute to the enhancement of quality of care for cancer survivors and efficiency in the broader cancer system.
Reply to E. Parkin et al
Authors: Christina M. Dieli-Conwright, Kerry S. Courneya, Wendy Demark-Wahnefried, Nathalie Sami, Kyuwan Lee, Thomas A. Buchanan, Darcy Spicer, Debu Tripathy, Leslie Bernstein, Joanne E. Mortimer
Journal: Journal of Clinical Oncology (2018)