tbuckley/cabot-search huggingface dataset:
Case-control study of hormone receptor expression in benign breast and cancer risk.
Authors: Caroline Fenger Healy, Vamsi Parimi, Seema Ahsan Khan, Jun Wang
Journal: Journal of Clinical Oncology (2015)

539 Background: Previous studies have shown that hormone receptor expression in non-proliferative epithelium (NPE) indicates increased breast cancer risk, whereas other studies have been null. We assessed estrogen receptor (ER), progesterone receptor (PR) and Ki67 expression in NPE of newly diagnosed breast cancer cases and benign disease controls using contemporary immunohistochemical (IHC) methods and digital image analysis. Methods: Formalin-fixed paraffin-embedded breast samples (171 cases and 169 age-matched controls) were collected from women treated between 1994-1999. 4-µm sections were stained for ER (ThermoScientific/SP1, 1:200-pH6), PR (Dako/M3569, 1:1600-pH6) and Ki67 (Dako/MIB-1, 1:100-pH6) on Leica Bond Max and Dako automated stainers. The NPE portions of the digitized slides were sampled in random fashion and evaluated blindly with Aperio Spectrum software. % positive cells were scored for ER, PR and Ki67 and categorized into quartiles. Wilcoxon rank-sum test and logistic regression with age adjustment were used for pairwise comparison. Spearman’s rank correlation test and one-way ANOVA test with Sidak adjustment were used for the correlation and comparison among multiple markers and subgroups. Results: The mean age was 49 years for cases and 48 years for controls. Overall, there was no significant difference between the cases and controls for ER, PR or Ki67 expression. In analyses stratified by menopausal (M) status, post-M ER % positivity was significantly higher in cases than controls (34.0 vs 29.8, OR = 1.49, p = 0.007). ER was significantly higher in post-M than in pre-M cases (p < 0.0001). ER and PR were positively correlated among cases (R = 0.433, p < 0.0001) and controls (R = 0.547, p < 0.0001). Ki67 was significantly lower in post-M than in pre-M controls (p = 0.004). Conclusions: ER expression in benign non-proliferative breast epithelium is significantly higher in postmenopausal cases, suggesting increased ER expression may indicate increased breast cancer risk in older women. ER % logistic regression on quartile (age-adjusted). Premenopausal Postmenopausal Control Case Control Case N 83 82 84 81 Median 27.5 26.4 29.8 34.0 95% CI 0.68-1.20 1.12-1.98 OR 0.90 1.49 P 0.49 0.007
Genomic changes of <i>AR</i> in ctDNA prior to enzalutamide in men with mCRPC after abiraterone acetate.
Authors: Leta Ko, Michael B. Lilly, Andrew W Hahn, Roberto Nussenzveig, Marcus Marie Moses, Elisa Ledet, Charlotte Manogue, Patrick Cotogno, Brian E. Lewis, Jodi Lyn Layton, Neeraj Agarwal, A. Oliver Sartor, Pedro C. Barata
Journal: Journal of Clinical Oncology (2019)

320 Background: Approximately 20-30% of men with metastatic castration-resistant prostate cancer (mCRPC) seem to respond to enzalutamide (ENZA) after prior exposure to abiraterone acetate and steroids (AA). The impact of genomic changes in androgen receptor (AR) gene in ctDNA and subsequent response to ENZA after prior AA exposure, is not entirely known. Methods: We performed a retrospective analysis of 28 mCRPC who were treated with ENZA after prior exposure to AA. Patients had NGS testing of ctDNA (Guardant 360) done post-AA and prior to ENZA. AR changes were defined by either amplification (amp; copy number ≥1) and/or mutations (mut; allele fraction ≥0.3%) in the AR gene. The primary endpoint of this study was time to PSA progression on enzalutamide. Correlations between genomic data and clinical outcomes were evaluated. Results: The 28 mCRPC patients had a median age of 67 (47-86), and 66.7% had a Gleason score 8-10. Metastases were found in bone (93%), lymph nodes (35.7%) and viscera (35%). Patients received ENZA after a median of 1 (1-5) treatment for CRPC. Patients were treated with prior AA for a median of 11.0 months (1.2-51.9) and median initial PSA at time of ENZA initiation was 35 ng/mL (1.52-356). The median time from ctDNA testing to ENZA start date was 0.9 months (range 0-5.6). Somatic changes in AR genes were detected in 36% (5/10 AR amp, 4/10 AR mut, 1/10 both). Other common alterations included 39% TP53, 11% DNA repair genes (2/3 BRCA2, 1/3 ATM), 7% PTEN. With a median follow-up of 8.9 months, 32% achieved PSA response (≥50%) and median time to PSA progression was 1.6 months (95% CI 1.0-2.2). On univariate analysis, lower Gleason scores (p = 0.021) and lack of AR changes (p = 0.042) were associated with PSA response to ENZA. Conclusions: In this cohort, responses to ENZA were associated with the absence of AR changes in ctDNA and less aggressive phenotypes. Prospective validation of this genomic association is required.
Abstract 040: Association of Physical Inactivity and Lifetime Risk of Heart Failure Among White and Black US Adults
Authors: Sadiya S Khan, Amanda E Paluch, Hongyan Ning, Jarett D Berry, Mercedes Carnethon, John T Wilkins, Donald M Lloyd-Jones
Journal: Circulation (2019)

Introduction: Adherence with the American Heart Association (AHA) guidelines for physical activity (AHA-PA) may reduce the risk of heart failure (HF). However, the association of AHA-PA in relation to sex and race-specific lifetime risk (LR) estimates of HF and years lived free of HF is not established. Therefore, we sought to examine the association of AHA-PA and burden of HF. Methods: We included individual-level pooled data from 5 population-based cohorts and stratified middle-aged participants (index age 40-59 years) free of cardiovascular disease (CVD) and HF at baseline by sex and race. We categorized AHA-PA as ideal (≥150 minutes/week), intermediate (1 to 149 minutes/week), or poor (0 minutes/week) and performed (1) modified Kaplan-Meier analysis to estimate LR of HF, (2) Irwin restricted mean to estimates years lived free of and with HF, and (3) competing Cox models (adjusted for age, smoking, education, body mass index [BMI], hypertension, and diabetes) to estimate joint cumulative risks for HF or death. Results: Of the 41,685 participants, 19% were black and 82% were women. Over median follow-up of 13.8 years, LR for incident HF was higher in individuals with poor compared with those who achieved ideal AHA-PA among women and black men, but not white men. Poor AHA-PA was associated with significantly fewer healthy years lived free of HF among black men (-4.9 years) compared with ideal AHA-PA, but was not significantly different among black women or white adults. Adjusted competing hazard ratios for incident HF among middle-aged black men with poor AHA-PA was 1.39 (95% confidence interval 1.02, 1.90) compared with individuals achieving ideal AHA-PA with similar findings among black (1.40 [1.07, 1.82]) or white women (1.79 [1.48, 2.17]) ( Table ). Discussion: Adherence with ideal AHA-PA is associated with lower risk of HF and greater proportion of life lived free of HF, particularly among black men. Public health policies promoting PA may mitigate the risk of HF in women and the racial disparities in HF in men.
Risk factors for postprostate biopsy infection.
Authors: Jonathan Shoag, Tianyi Sun, Morgan Pantuck, Michael A. Gorin, Edward M. Schaeffer, Art Sedrakyan, Jim Hu
Journal: Journal of Clinical Oncology (2019)

103 Background: Prostate biopsy is a common procedure that many U.S. men endure during their lifetime. Evidence suggests that the risk of post-biopsy infections is increasing. We aimed to characterize risk factors for post-biopsy infections using nationally representative data. Methods: We analyzed Surveillance, Epidemiology and End Results (SEER)-Medicare data to identify 246,299 male Medicare beneficiaries aged over 65 years who underwent prostate biopsy between 2001 and 2013. Multivariable logistic regression was used to assess risk factors for post-biopsy infection.The primary outcomes were any infection within 30 days of prostate biopsy, and infections requiring hospital admission within 30 days of biopsy. Results: In this cohort, 7.0% of men developed an infection within 30 days and 1.0% required hospital admission for infection. The vast majority of biopsies were performed transrectally (99.5%) without a rectal swab culture performed prior to biopsy to direct antimicrobial prophylaxis (99.7%). Risk factors for post-biopsy infection and hospitalization on multivariable analysis included age over 80 years, odds ratio (OR) 1.23 (95% confidence interval (CI) 1.17 to 1.29, for any infection, and OR 1.71 (95% CI 1.52 to 1.92) for infection requiring hospitalization, Black race, OR 1.29 (95% CI 1.23 to 1.35) for any infection, and OR 1.41 (95% CI 1.25 to 1.58) for hospitalization, and Hispanic ethnicity, OR 1.61 (95% CI 1.46 to 1.77) for any infection, and OR 1.92 (95% CI 1.52 to 2.42) for hospitalization. The risk of infection also increased with Charlson score of 3 or greater, OR 1.32 (95% CI 1.25 to 1.39), and OR 2.04 (95% CI 1.73 to 2.40) for any infection or hospitalization, respectively. High surgeon volume (&gt;11.6 cases) was protective, OR 0.92 (95% CI 0.88 to 0.96) for any infection, and OR 0.76 (95% CI 0.69 to 0.85) for hospitalization. Conclusions: Among other factors, we identify patient age, Charlson score, race, ethnicity, and surgeon volume as significant predictors of post-prostate biopsy infection and hospitalization. These results should aid in identifying patients who may benefit from alternative techniques, such as targeted or augmented antimicrobial prophylaxis, or transperineal biopsy, to minimize this common source of morbidity.
Divining responder populations from survival data
Authors: R. Rahman, S. Ventz, G. Fell, A.M. Vanderbeek, L. Trippa, B.M. Alexander
Journal: Annals of Oncology (2019)

Biomarkers that predict treatment response are the foundation of precision medicine in clinical decision-making and have the potential to significantly improve the efficiency of clinical trials. Such biomarkers may be identified before clinical testing but many trials enroll unselected populations. We hypothesized that time-varying treatment effects in unselected trials may result from identifiable responder subpopulations that may have associated biomarkers.We first simulated scenarios of clinical trials with biomarker populations of varying prevalence and prognostic and predictive associations to illustrate the impact of subgroup-specific effects on overall population estimates. To show a real-world example of time-dependent treatment effects resulting from a prognostic and predictive biomarker, we re-analyzed data from a published clinical trial (RTOG, Radiation Therapy Oncology Group, 9402). We then demonstrated a quantitative framework to fit survival data from clinical trials using statistical models incorporating known estimates of biomarker prevalence and prognostic value to prioritize predictive biomarker hypotheses.Our simulation studies demonstrate how biomarker subgroups that are both predictive and prognostic can manifest as time-dependent treatment effects in overall populations. RTOG 9402 provides a representative example where 1p/19q co-deletion and IDH mutation biomarker-specific effects led to time-varying treatment effects and a considerable deviation from proportional hazards in the overall trial population. Finally, using biomarker data from The Cancer Genome Atlas, we were able to generate statistical models that correctly identified and prioritized a commonly used biomarker through retrospective analysis of published clinical trial data.Biomarkers that are both predictive and prognostic can result in characteristic changes in survival results. Retrospectively analyzing survival data from clinical trials may highlight potential indications for which an underlying predictive biomarker may be found.
Abstract P093: A Nutrition Education Program Through the Farmer’s Market: Lessons Learned From Community-based Research in North Dakota
Authors: Amir Alakaam
Journal: Circulation (2019)

Introduction: More than 32% of adults have obesity in North Dakota (ND), cardiovascular diseases and cancer are the leading causes of death, and at least one in ten adults has diabetes in ND. Healthy eating habit has a protective role against chronic diseases and obesity. A community-based nutrition education program was implemented to identify effective and approachable strategies for developing a long-term intervention that increases fruits and vegetables intake and reduces risk of chronic diseases in ND community. Hypothesis: (1) Nutrition education would increase intake of fruits and vegetables among participants. (2) Participants who received compensation would be more likely to increase their consumption of fresh fruits and vegetables. Method: The pilot program was delivered through the farmer’s market in ND. We delivered six nutrition education sessions focus on the importance of fruits and vegetables on diet, and developing healthy skills related to fruits and vegetables purchasing and cooking. Participants earned a gift certificate at the end of session. Data collected through post-assessment questionnaire. Results: Two hundred and thirty nine participants enrolled and benefited from the program. We found significant increase in fruits and vegetables intake among participants. Results show that increasing access to fresh fruits and vegetables, and providing education about healthy food consumption encouraged market’s visitors to purchase fruits and vegetables. Conclusion: Nutrition education program through farmer’s market has the potential to increase fruits and vegetables intake. The finding suggests that researcher should implement nutrition education intervention as an approach to positively influence eating habits among community.
Five-year analysis of the phase II NeoSphere trial evaluating four cycles of neoadjuvant docetaxel (D) and/or trastuzumab (T) and/or pertuzumab (P).
Authors: Luca Gianni, Tadeusz Pienkowski, Young-Hyuck Im, Ling-Ming Tseng, Mei-Ching Liu, Ana Lluch, Elzbieta Staroslawska, Juan de la Haba-Rodriguez, Seock-Ah Im, Jose Luiz Pedrini, Brigitte Poirier, Paolo Morandi, Vladimir Semiglazov, Vichien Srimuninnimit, Giulia Valeria Bianchi, Virginia McNally, Hannah Douthwaite, Graham Ross, Pinuccia Valagussa
Journal: Journal of Clinical Oncology (2015)

505 Background: InNeoSphere, four cycles of T+D, P+T+D, P+T, or P+D, followed by surgery and adjuvant chemotherapy plus conventional T, were evaluated in 417 women with locally advanced, inflammatory, or early HER2-positive breast cancer. The addition of P to T+D led to a statistically significant and clinically meaningful 16.8% increase (95% confidence interval [CI], 3.5–30.1; P = .0141) in pathologic complete response rate (pCR) in the breast (bpCR, ypT0/is; primary endpoint), and a 17.8% increase in total pCR in the breast and axilla (tpCR, ypT0/is, ypN0). Methods: A pre-planned descriptive intent-to-treat analysis was conducted 5 years after randomization of the last patient, to evaluate disease-free survival (DFS; time from surgery until progression or death) and progression-free survival (PFS; time from randomization until progression or death, equivalent to the commonly used definition of event-free survival). Results: Three-year survival rates, hazard ratios (HRs), and 95% CIs for the main analysis of P+T+D compared with T+D are summarized in the table. In the P+T and P+D arms, respectively, 3-year survival rates were 88% and 84% for DFS, and 81% and 82% for PFS. Across all four treatment arms pooled, for all patients who achieved tpCR versus all patients who did not achieve tpCR, the HR for DFS was 0.68 (95% CI, 0.36–1.26) and the HR for PFS was 0.54 (95% CI, 0.29–1.00). Conclusions: Longer-term outcomes as defined by three-year survival rates, are in line with the results of the primary endpoint (bpCR), suggesting a benefit of P added to T+D that persists over time despite use of identical adjuvant therapy in the P+T+D and T+D arms. These results also support the association between pCR and improvements in long-term outcomes. Clinical trial information: NCT00545688. T+D (n = 107) P+T+D (n = 107) DFS 3-year Kaplan–Meier survival estimate, % 85 92 HR* – 0.60 (95% CI) – (0.28–1.27) PFS 3-year Kaplan–Meier survival estimate, % 86 90 HR* – 0.69 (95% CI) – (0.34–1.40) * Compared with T+D
KRAS, NRAS and BRAF Mutations Are Highly Enriched in TRI12 Chronic Lymphocytic Leukemia and Are Associated to Shorter Time to First Treatment
Authors: Elena Vendramini, Riccardo Bomben, Federico Pozzo, Dania Benedetti, Maria Francesca Rossi, Michele Dal Bo, Gabriele Pozzato, Francesco Zaja, Annalisa Chiarenza, Francesco Di Raimondo, Giovanni Del Poeta, Valter Gattei, Antonella Zucchetto
Journal: Blood (2018)
"Identification of Variables that led to improvement in Breast Cancer Screening.
Authors: Hyma Vani Polimera, Astha Agarwal, Gloria Fioravanti, Bonnie Coyle
Journal: Journal of Clinical Oncology (2015)

e12573 Background: Breast Cancer (BCa) is the second most common cancer among women and second leading cause of cancer deaths in United States. Five-year survival rate for localized BCa is 98%, whereas stage 4 BCa declines to 20%. National mammogram rate for the year 2012 was 65% but was only 48% at our Community Medical Center (CMC). Our goal was to increase the compliance rates of screening mammogram by at least 10% over a 10 month period by utilizing American Cancer Society grant. Methods: Baseline data was obtained by retrospective chart review of women between ages 50 to 74 who visited CMC from January 2012 to December 2012 (Group 1). IRB exemption was granted. A community academic partnership was instituted. The team consisted of medical providers, community health workers and epidemiologist. Patient and physician barriers for mammogram completion were recognized. Monthly breast cancer awareness camps were conducted at CMC and various places in the community. Structured education was provided. Tracking process was developed to ensure completion of mammograms. Assistance was provided to patients based on their specific barriers for transport, scheduling appointments, education and stepped reminders were created. Clinical outcome data was prospectively collected over a 10month period from June 2013 to March 2014 for the women of the same age group who visited CMC (Group 2). Results: Mammogram completion rates in Group 1:n = 1642 was 48% and in Group 2:n = 1361 was 61.3. Based on a t-test, the difference was statistically significant (p < 0.0001). Based on chi square test, there was a significant association between ethnicity/race and screening mammograms (p < 0.0001), with a higher improvement seen in Hispanics compared to Caucasian, Asian, African American and native Americans. Screening mammogram rate for Hispanics was 11.4% prior to intervention, whereas it was 64.5% post intervention. Based on chi square test, there was a significant improvement of screening mammogram rate (p < 0.0001), in both insured and uninsured patients. Conclusions: With targeted interventions, including provider based referral, education, stepped reminder and using a patient navigator system; screening mammogram rate improved beyond our anticipated goal.
Higher intake of cholesterol or eggs linked to increased risk of cardiovascular disease and death, finds study
Authors: Susan Mayor
Journal: BMJ (2019)

Higher consumption of dietary cholesterol or eggs is associated with increased risk of new onset cardiovascular disease and mortality, a pooled analysis of long term follow-up studies of US adults has shown.

The study pooled individual participant data from six prospective US cohorts looking at dietary intake and cardiovascular disease using data collected from 29 615 adults followed up for a median of 17.5 years between 1985 and 2016.1 The authors harmonised self reported diet data across the studies using a standardised protocol.

Results, reported in JAMA …
Centrosomes take center-stage: Comparative analysis of centrosome amplification in African American and European American pancreatic adenocarcinomas patients.
Authors: Karuna Mittal, Vaishali Pannu, Sergey Klimov, Padmashree C.G. Rida, Shristi Bhattarai, Michelle D. Reid, Ritu Aneja
Journal: Journal of Clinical Oncology (2015)

e15257 Background: Mortality from pancreatic cancer is higher in African-Americans (AA) compared to European Americans (EA). Although recent studies have focused on identification of gene expression signatures in whole tumors with variable metastatic potential, a disparity at the organelle-level between tumors of differing aggressiveness and metastatic potential has remained unexplored. Given the long-standing association between centrosome amplification (CA) and aggressiveness, we examined the centrosomal profile of two aggressive pancreatic cell lines MIA Paca and HPAF-II. Our observations indicated considerable CA in these cell lines thus providing a rationale to hypothesize that CA may underlie the difference in disease progression between AA and EA pancreatic adenocarcinomas. To test this hypothesis, we have developed an innovative method to quantitate the degree of CA (both numeral and structural) within tumor samples and defined a measurable index called the Centrosome Amplification Score (CAS). Methods: Tissue specimens from 39 EA and 29 AA pancreatic adenocarcinomas were immunostained for centrosomes (γ-tubulin) and nuclei (Hoechst) and 10 regions of interest (ROIs) per sample were captured using immunofluorescence confocal imaging. The cumulative CAS was obtained for each ROI as CASTotal = CASi + CASm (where CASi and CASm are CAS for individual centrosomes and structurally aberrant megacentrosomes, respectively). Results: AA tumors exhibit higher mean CASi (16.75 vs 13.6) and CASTotal (26.09 vs 22.48) than grade-matched EA suggesting racial disparity at the organellar level (p < 0.05). We also found that Grade 2 tumors exhibited higher mean CASTotal (18.9 vs 11.1) compared to Grade 3 regardless of race (p < 0.05). Conclusions: Our results suggest that an aggressive disease course in AA can be attributed to higher degree and severity of CA in AA as compared to EA patients, which may render AA more sensitive to centrosome targeting drugs. Our data compellingly suggest the potential usefulness of CAS in enabling patient stratification for individualized treatment, and eliminating ethnic disparities in pancreatic cancer outcomes.
<i>M</i><i>ycobacterium abscessus</i> pulmonary disease: individual patient data meta-analysis
Authors: Nakwon Kwak, Margareth Pretti Dalcolmo, Charles L. Daley, Geoffrey Eather, Regina Gayoso, Naoki Hasegawa, Byung Woo Jhun, Won-Jung Koh, Ho Namkoong, Jimyung Park, Rachel Thomson, Jakko van Ingen, Sanne M.H. Zweijpfenning, Jae-Joon Yim
Journal: European Respiratory Journal (2019)

Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus , M. abscessus subsp. massiliense or M. abscessus subsp. bolletii , is challenging. We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment. Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense . For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36–5.10). For patients with M. abscessus subsp. abscessus , the use of azithromycin (aOR 3.29, 95% CI 1.26–8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05–1.99) or imipenem (aOR 7.96, 95% CI 1.52–41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense , the choice among these drugs was not associated with treatment outcomes. Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus .