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1.
Animal ; 17(10): 100969, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37742501

ABSTRACT

Fast, accurate, and reliable estimates of backfat depth, loin depth, and intramuscular fat percentage in swine breeding stock are used to increase genetic improvement and farm profitability. The objective of this study was to develop an equation-based model for the estimation of swine backfat depth, loin depth, and intramuscular fat percentage estimates obtained from longitudinal ultrasound images. Images were collected from purebred Duroc (n = 230), purebred Large White (n = 154), and commercial (n = 190) pigs born in January 2021 at three farms located in North Carolina. An Exapad ultrasound machine captured longitudinal images across the 10th to 13th ribs at 182 (±12.8 SD) days of pig age. The total number of images processed for Duroc, Large White, and commercial pigs was 1 385, 928, and 1 168 images, respectively. To establish a standard measurement for model comparison, trained personnel following standard company procedures using the BioSoft Toolbox (v4.0.1.2; Biotronics Inc., Ames, IA) obtained backfat and loin depth measurements from the images. Longissimus muscle intramuscular fat percentage was predicted using near-infrared spectroscopy at approximately 22 h postmortem. Backfat and loin depth estimation were conducted only for commercial pigs (n = 190) while intramuscular fat estimation was conducted on all pigs (n = 574). Average backfat depth, loin depth, and intramuscular fat percentage were 14.6 (±2.6 SD) mm, 63.7 (±5.5 SD) mm, and 2.21 (±0.82 SD) %. Image analysis and estimation model development were conducted in MATLAB R2021a. Edge detection via the image gradient was applied to segment ultrasound images into backfat, loin, and rib regions. Segmented images were used to estimate backfat depth, loin depth, and loin intramuscular fat percentage. After image quality control and filtering, the image inclusion rate for each breed-trait combination ranged from 76 to 97%. All Duroc and commercial pigs and 97% of Large White pigs were represented by at least one image for trait estimation. Coefficient of determination of models for the estimation of backfat depth, loin depth, and intramuscular fat percentage were 0.58, 0.57, and 0.56, respectively. Root mean square error of backfat depth, loin depth, and intramuscular fat estimation were 1.65 mm, 3.58 mm, and 0.54%, respectively. Results demonstrate the feasibility of using ultrasound image gradient and an equation-based approach to estimate swine backfat and loin depth, and intramuscular fat percentage. This equation-based approach to estimate carcass traits in live swine can enhance genetic improvement.

2.
BMC Cancer ; 20(1): 392, 2020 May 06.
Article in English | MEDLINE | ID: mdl-32375735

ABSTRACT

BACKGROUND: The ABCSG-28 trial compared primary surgery followed by systemic therapy versus primary systemic therapy without surgery in patients with de novo stage IV BC. The present report describes QoL results of this trial. METHODS: Ninety patients with primary operable MBC were randomised to surgery of the primary tumor followed by systemic therapy or to primary systemic therapy without surgery. QoL analyses covering the results at baseline, 6,12,18 and 24 months follow up of 79 (88%) patients, was assessed with the EORTC QLQ-C30 and QLQ-BR23 questionnaires. RESULTS: There were no statistically significant differences in any of the scales of the QLQ-C30 and QLQ-BR23 questionnaires between the two groups over the time. Baseline global health status and physical functioning were predictors for OS (patients with a higher score lived longer (p=0.0250, p=0.0225; p=0.0355, p=0.0355)). Global health status, social functioning scale, breast symptoms and future perspective were predictors for longer TTPd (p=0.0244; p=0.0140, p=0.020; p=0.0438, p=0.0123). Patients in both arms reported significant improvement on the emotional functioning scale. Cognitive functioning decreased over time in both groups. Younger women had clinically relevant better physical and sexual functioning scores (p=0.039 and 0.024). CONCLUSION: Primary surgery does not improve nor alter QoL of patients with de novo stage IV BC. Global health status and physical functioning were predictors for OS and could be use as additional marker for prediction of OS and TTTd in patients with de novo stage IV BC. TRIAL REGISTRATION: The trial is registered on clinicaltrial.gov (NCT01015625, date of registration:18/11/2009).


Subject(s)
Breast Neoplasms/surgery , Mastectomy/mortality , Patient Reported Outcome Measures , Quality of Life , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Metastasis , Prognosis , Prospective Studies , Survival Rate , Young Adult
3.
Breast Cancer Res Treat ; 175(2): 389-399, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30796651

ABSTRACT

PURPOSE: The WSG-PRIMe Study prospectively evaluated the impact of the 70-gene signature MammaPrint® (MP) and the 80-gene molecular subtyping assay BluePrint® on clinical therapy decisions in luminal early breast cancer. METHODS: 452 hormone receptor (HR)-positive and HER2-negative patients were recruited (N0, N1). Physicians provided initial therapy recommendations based on clinicopathological factors. After prospective risk classification by MammaPrint/BluePrint was revealed, post-test treatment recommendations and actual treatment were recorded. Decisional Conflict and anxiety were measured by questionnaires. RESULTS: Post-test switch (in chemotherapy (CT) recommendation) occurred in 29.1% of cases. Overall, physician adherence to MP risk assessment was 92.3% for low-risk and 94.3% for high-risk MP scores. Adherence was remarkably high in "discordant" groups: 74.7% of physicians initially recommending CT switched to CT omission following low-risk MP scores; conversely, 88.9% of physicians initially recommending CT omission switched to CT recommendations following high-risk MP scores. Most patients (99.2%) recommended to forgo CT post-test and 21.3% of patients with post-test CT recommendations did not undergo CT; among MP low-risk patients with pre-test and post-test CT recommendations, 40% did not actually undergo CT. Luminal subtype assessment by BluePrint was discordant with IHC assessment in 34% of patients. Patients' State Anxiety scores improved significantly overall, particularly in MP low-risk patients. Trait Anxiety scores increased slightly in MP high risk and decreased slightly in MP low-risk patients. CONCLUSIONS: MammaPrint and BluePrint test results strongly impacted physicians' therapy decisions in luminal EBC with up to three involved lymph nodes. The high adherence to genetically determined risk assessment represents a key prerequisite for achieving a personalized cost-effective approach to disease management of early breast cancer.


Subject(s)
Breast Neoplasms/drug therapy , Chemotherapy, Adjuvant , Transcriptome/genetics , Adult , Aged , Aged, 80 and over , Breast Neoplasms/classification , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cost-Benefit Analysis , Decision Making , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , In Situ Hybridization, Fluorescence , Middle Aged , Receptor, ErbB-2/genetics , Receptors, Estrogen/genetics , Receptors, Progesterone/genetics , Treatment Outcome
4.
J Anim Breed Genet ; 135(1): 5-13, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29178316

ABSTRACT

The objective of this study was to compare and determine the optimal validation method when comparing accuracy from single-step GBLUP (ssGBLUP) to traditional pedigree-based BLUP. Field data included six litter size traits. Simulated data included ten replicates designed to mimic the field data in order to determine the method that was closest to the true accuracy. Data were split into training and validation sets. The methods used were as follows: (i) theoretical accuracy derived from the prediction error variance (PEV) of the direct inverse (iLHS), (ii) approximated accuracies from the accf90(GS) program in the BLUPF90 family of programs (Approx), (iii) correlation between predictions and the single-step GEBVs from the full data set (GEBVFull ), (iv) correlation between predictions and the corrected phenotypes of females from the full data set (Yc ), (v) correlation from method iv divided by the square root of the heritability (Ych ) and (vi) correlation between sire predictions and the average of their daughters' corrected phenotypes (Ycs ). Accuracies from iLHS increased from 0.27 to 0.37 (37%) in the Large White. Approximation accuracies were very consistent and close in absolute value (0.41 to 0.43). Both iLHS and Approx were much less variable than the corrected phenotype methods (ranging from 0.04 to 0.27). On average, simulated data showed an increase in accuracy from 0.34 to 0.44 (29%) using ssGBLUP. Both iLHS and Ych approximated the increase well, 0.30 to 0.46 and 0.36 to 0.45, respectively. GEBVFull performed poorly in both data sets and is not recommended. Results suggest that for within-breed selection, theoretical accuracy using PEV was consistent and accurate. When direct inversion is infeasible to get the PEV, correlating predictions to the corrected phenotypes divided by the square root of heritability is adequate given a large enough validation data set.


Subject(s)
Breeding , Genomics , Litter Size/genetics , Models, Statistical , Pedigree , Swine/genetics , Swine/physiology , Animals , Female , Male
5.
J Anim Sci ; 95(8): 3370-3380, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28805927

ABSTRACT

Utilization of feed in livestock species consists of a wide range of biological processes, and therefore, its efficiency can be expressed in various ways, including direct measurement, such as daily feed intake, as well as indicator measures, such as feeding behavior. Measuring feed efficiency is important to the swine industry, and its accuracy can be enhanced by using automated feeding systems, which record feed intake and associated feeding behavior of individual animals. Each automated feeder space is often shared among several pigs and therefore raises concerns about social interactions among pen mates with regard to feeding behavior. The study herein used a data set of 14,901 Duroc boars with individual records on feed intake, feeding behavior, and other off-test traits. These traits were modeled with and without the random spatial effect of Pen_Room, a concatenation of room and pen, or random social interaction among pen mates. The nonheritable spatial effect of common Pen-Room was observed for traits directly measuring feed intake and accounted for up to 13% of the total phenotypic variance in the average daily feeding rate. The social interaction effect explained larger proportions of phenotypic variation in all the traits studied, with the highest being 59% for ADFI in the group of feeding behaviors, 73% for residual feed intake (RFI; RFI4 and RFI6) in the feed efficiency traits, and 69% for intramuscular fat percentage in the off-test traits. After accounting for the social interaction effect, residual BW gain and RFI and BW gain (RIG) were found to have the heritability of 0.38 and 0.18, respectively, and had strong genetic correlations with growth and off-test traits. Feeding behavior traits were found to be moderately heritable, ranging from 0.14 (ADFI) to 0.52 (average daily occupation time), and some of them were strongly correlated with feed efficiency measures; for example, there was a genetic correlation of 0.88 between ADFI and RFI6. Our work suggested that accounting for the social common pen effect was important for estimating genetic parameters of traits recorded by the automated feeding system. Residual BW gain and RIG appeared to be two robust measures of feed efficiency. Feeding behavior measures are worth further investigation as indicators of feed efficiency.


Subject(s)
Feeding Behavior , Swine/physiology , Animals , Eating , Male , Phenotype
6.
J Anim Sci ; 93(11): 5153-63, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26641035

ABSTRACT

Litter size at d 5 (LS5) has been shown to be an effective trait to increase total number born (TNB) while simultaneously decreasing preweaning mortality. The objective of this study was to determine the optimal litter size day for selection (i.e., other than d 5). Traits included TNB, number born alive (NBA), litter size at d 2, 5, 10, 30 (LS2, LS5, LS10, LS30, respectively), litter size at weaning (LSW), number weaned (NW), piglet mortality at d 30 (MortD30), and average piglet birth weight (BirthWt). Litter size traits were assigned to biological litters and treated as a trait of the sow. In contrast, NW was the number of piglets weaned by the nurse dam. Bivariate animal models included farm, year-season, and parity as fixed effects. Number born alive was fit as a covariate for BirthWt. Random effects included additive genetics and the permanent environment of the sow. Variance components were plotted for TNB, NBA, and LS2 to LS30 using univariate animal models to determine how variances changed over time. Additive genetic variance was minimized at d 7 in Large White and at d 14 in Landrace pigs. Total phenotypic variance for litter size traits decreased over the first 10 d and then stabilized. Heritability estimates increased between TNB and LS30. Genetic correlations between TNB, NBA, and LS2 to LS29 with LS30 plateaued within the first 10 d. A genetic correlation with LS30 of 0.95 was reached at d 4 for Large White and at d 8 for Landrace pigs. Heritability estimates ranged from 0.07 to 0.13 for litter size traits and MortD30. Birth weight had an h of 0.24 and 0.26 for Large White and Landrace pigs, respectively. Genetic correlations among LS30, LSW, and NW ranged from 0.97 to 1.00. In the Large White breed, genetic correlations between MortD30 with TNB and LS30 were 0.23 and -0.64, respectively. These correlations were 0.10 and -0.61 in the Landrace breed. A high genetic correlation of 0.98 and 0.97 was observed between LS10 and NW for Large White and Landrace breeds, respectively. This would indicate that NW could possibly be used as an effective maternal trait, given a low level of cross-fostering, to avoid back calculating litter size traits from piglet records. Litter size at d 10 would be a compromise between gain in litter size at weaning and minimizing the potentially negative effects of the nurse dam and direct additive genetics of the piglets, as they are expected to increase throughout lactation.


Subject(s)
Genetic Variation , Litter Size/genetics , Swine/genetics , Animals , Birth Weight/genetics , Breeding , Female , Lactation/genetics , Parturition/genetics , Phenotype , Pregnancy , Swine/physiology , Weaning
7.
Ann Oncol ; 26(2): 313-20, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25403582

ABSTRACT

BACKGROUND: Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months. PATIENTS AND METHODS: Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points. RESULTS: After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. CONCLUSION: These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term. CLINICALTRIALSGOV: NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Density Conservation Agents/administration & dosage , Breast Neoplasms/drug therapy , Adult , Anastrozole , Antineoplastic Agents, Hormonal/administration & dosage , Breast Neoplasms/mortality , Diphosphonates/administration & dosage , Disease-Free Survival , Female , Follow-Up Studies , Goserelin/administration & dosage , Humans , Imidazoles/administration & dosage , Kaplan-Meier Estimate , Middle Aged , Nitriles/administration & dosage , Premenopause , Tamoxifen/administration & dosage , Triazoles/administration & dosage , Zoledronic Acid
8.
Ann Oncol ; 25(2): 339-45, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24347518

ABSTRACT

BACKGROUND: PAM50 is a 50-gene test that is designed to identify intrinsic breast cancer subtypes and generate a Risk of Recurrence (ROR) score. It has been developed to be carried out in qualified routine hospital pathology laboratories. PATIENTS AND METHODS: One thousand four hundred seventy-eight postmenopausal women with estrogen receptor (ER)+ early breast cancer (EBC) treated with tamoxifen or tamoxifen followed by anastrozole from the prospective randomized ABCSG-8 trial were entered into this study. Patients did not receive adjuvant chemotherapy. RNA was extracted from paraffin blocks and analyzed using the PAM50 test. Both intrinsic subtype (luminal A/B, HER2-enriched, basal-like) and ROR score were calculated. The primary analysis was designed to test whether the continuous ROR score adds prognostic value in predicting distant recurrence (DR) over and above standard clinical variables. RESULTS: In all tested subgroups, ROR score significantly adds prognostic information to the clinical predictor (P<0.0001). PAM50 assigns an intrinsic subtype to all cases, and the luminal A cohort had a significantly lower ROR at 10 years compared with Luminal B (P<0.0001). Significant and clinically relevant discrimination between low- and high-risk groups occurred also within all tested subgroups. CONCLUSION(S): The results of the primary analysis, in combination with recently published results from the ATAC trial, constitute Level 1 evidence for clinical validity of the PAM50 test for predicting the risk of DR in postmenopausal women with ER+ EBC. A 10-year metastasis risk of <3.5% in the ROR low category makes it unlikely that additional chemotherapy would improve this outcome-this finding could help to avoid unwarranted overtreatment. CLINICAL TRIAL NUMBER: ABCSG 8: NCT00291759.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/pathology , Neoplasm Recurrence, Local/prevention & control , Adult , Aged , Anastrozole , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Clinical Trials as Topic , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Nitriles/therapeutic use , Postmenopause , Prognosis , Proportional Hazards Models , Receptor, ErbB-2/metabolism , Retrospective Studies , Risk , Risk Assessment , Tamoxifen/therapeutic use , Transcriptome , Treatment Outcome , Triazoles/therapeutic use
9.
Eur J Cancer ; 49(18): 3773-9, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23992641

ABSTRACT

BACKGROUND: The cost-effectiveness of the 70-gene signature (70-GS) (MammaPrint®) has earlier been estimated using retrospective validation data. Based on the prospective 5-year survival data of the microarRAy-prognoSTics-in-breast-cancER (RASTER) study, the aim here was to evaluate the cost-effectiveness reflecting the actual use in clinical practice, including reality-based compliance rates. METHODS: Costs and outcomes (quality-adjusted-life-years (QALYs)) were calculated in node-negative (N-) patients included in the RASTER study (n=427). Sensitivity and specificity of the 70-gene and Adjuvant! Online (AO) were based on 5-year distant-disease-free survival (DDFS). Subgroup analyses were performed for two groups for whom benefit of the 70-gene had earlier been reported: (1) ductal, oestrogen receptor-positive (ER+), tumour diameter 10-30 mm, grade II, age 40-70; (2) ductal, oestrogen receptor-positive, tumour diameter 5-30 mm, grade II/III and age 40-70. RESULTS: Based on 5-year survival data, the cost-effectiveness of the 70-gene signature versus AO was prospectively confirmed. The total health care costs per patient were €26,786 for the 70-gene and €29,187 for AO. The quality adjusted life years yielded 12.49 and 11.88, respectively. The subgroups retrieved slightly higher life gains and higher costs, but all resulted finally in a favourable position for the 70-gene signature. CONCLUSIONS: The use of the 70-gene signature, as judged appropriate by doctors and patients and supported by a low risk 70-gene signature as an oncological safe choice, was also found to be cost-effective.


Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Adult , Aged , Breast Neoplasms/diagnosis , Chemotherapy, Adjuvant/economics , Cost-Benefit Analysis , Female , Humans , Markov Chains , Middle Aged , Oligonucleotide Array Sequence Analysis/economics , Outcome Assessment, Health Care/economics , Prognosis , Prospective Studies , Quality-Adjusted Life Years , Receptors, Estrogen/metabolism , Risk Assessment/economics , Survival Analysis , Time Factors , Tumor Burden/drug effects
10.
Int J Cancer ; 133(4): 929-36, 2013 Aug 15.
Article in English | MEDLINE | ID: mdl-23371464

ABSTRACT

The 70-gene signature (MammaPrint™) has been developed on retrospective series of breast cancer patients to predict the risk of breast cancer distant metastases. The microarRAy-prognoSTics-in-breast-cancER (RASTER) study was the first study designed to prospectively evaluate the performance of the 70-gene signature, which result was available for 427 patients (cT1-3N0M0). Adjuvant systemic treatment decisions were based on the Dutch CBO 2004 guidelines, the 70-gene signature and doctors' and patients' preferences. Five-year distant-recurrence-free-interval (DRFI) probabilities were compared between subgroups based on the 70-gene signature and Adjuvant! Online (AOL) (10-year survival probability <90% was defined as high-risk). Median follow-up was 61.6 months. Fifteen percent (33/219) of the 70-gene signature low-risk patients received adjuvant chemotherapy (ACT) versus 81% (169/208) of the 70-gene signature high-risk patients. The 5-year DRFI probabilities for 70-gene signature low-risk (n = 219) and high-risk (n = 208) patients were 97.0% and 91.7%. The 5-year DRFI probabilities for AOL low-risk (n = 132) and high-risk (n = 295) patients were 96.7% and 93.4%. For 70-gene signature low-risk-AOL high-risk patients (n = 124), of whom 76% (n = 94) had not received ACT, 5-year DRFI was 98.4%. In the AOL high-risk group, 32% (94/295) less patients would be eligible to receive ACT if the 70-gene signature was used. In this prospective community-based observational study, the 5-year DRFI probabilities confirmed the additional prognostic value of the 70-gene signature to clinicopathological risk estimations such as AOL. Omission of adjuvant chemotherapy as judged appropriate by doctors and patients and instigated by a low-risk 70-gene signature result, appeared not to compromise outcome.


Subject(s)
Breast Neoplasms/pathology , Adult , Female , Humans , Middle Aged , Probability , Prospective Studies , Survival Rate
11.
Q J Nucl Med Mol Imaging ; 56(5): 447-58, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23069924

ABSTRACT

Assessing bone metastases is often beyond the scope of plain - film radiography, and nuclear imaging in particular with bone scintigraphy has proved the mainstay for detection of bony disease for over 40 years. Bone scanning with 99mTechnetium - labeled diphosphonates relies on the detection of pathological osteoblastic response elicited from malignant cells. This technique offers the advantage of whole body examination, low cost, availability and high sensitivity. However, it suffers from relative low specificity. The addition of single-photon emission computed tomography (SPECT) to bone scintigraphy has markedly improved the diagnostic benefit. Although the accuracy of SPECT is significantly higher than that of planar scintigraphy, there is still room for improvement of anatomic localization and morphological characterization, a limitation that has currently been mainly overcome with the upcoming of combined SPECT-CT (computed tomography). Positron emission tomography (PET), a modality with higher spatial resolution than that of SPECT can be particularly helpful in detecting small lesions. Moreover, PET imaging using various specific radiotracers has the advantage of detecting malignant disease in both bone and soft tissues. It is highly sensitive mainly in detecting early bone marrow as well as for diagnosing lytic bony metastases and can be also reliably used to monitor therapy response. In this review, we present the current role of SPECT and PET in the imaging of skeletal metastases from prostate cancer.


Subject(s)
Bone Neoplasms/diagnostic imaging , Bone Neoplasms/secondary , Prostatic Neoplasms/pathology , Humans , Male , Positron-Emission Tomography , Radiopharmaceuticals , Tomography, Emission-Computed, Single-Photon , Whole Body Imaging
12.
Br J Cancer ; 106(3): 440-6, 2012 Jan 31.
Article in English | MEDLINE | ID: mdl-22233926

ABSTRACT

BACKGROUND: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. METHODS: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). CONCLUSION: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.


Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/secondary , Breast Neoplasms/epidemiology , Receptor, ErbB-2/metabolism , Adult , Aged , Aged, 80 and over , Austria/epidemiology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lung Neoplasms/secondary , Middle Aged , Neoplasm Staging , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective Studies
13.
J Anim Sci ; 89(4): 935-42, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21148777

ABSTRACT

The objective was to estimate correlations of gilt estrus, puberty, growth, composition, and structural conformation traits with first-litter reproductive measures. Four groups of gilts (n = 1,225; Genetic Improvement Services of NC, Newton Grove, NC) entered the NC Swine Evaluation Station (Clayton, NC) averaging 162 d of age and were observed daily for symptoms of estrus. Once symptoms of first estrus were observed in 70% of gilts, recording of symptoms of estrus in all gilts occurred every 12 h for 30 d, utilizing fence-line boar contact. Subjective estrous traits were maximum and total strength of standing reflex, as observed with and without the presence of a boar, and strength of vulva reddening and swelling. Objective estrous traits consisted of vulva redness, vulva width, length of estrus, and age at puberty. Growth and composition traits included BW at puberty, days to 114 kg, and 10th rib backfat and LM area at 114 kg and at puberty. Subjective structural conformation traits were muscle mass, rib width, front leg side view, rear leg side view, front legs front view, rear legs rear view, and locomotion. First-litter sow traits included if gilt farrowed (Stay), age at first farrowing (AFF), total number of piglets born (TNB), and weaning to conception interval (WCI). Variance components were estimated using an animal model with AIREMLF90 for linear traits and THRGIBBS1F90 for categorical traits. Heritability estimates for Stay, AFF, and TNB were 0.14, 0.22, and 0.02, respectively. Genetic correlations between length of estrus, the standing reflex traits, and age at puberty with Stay were 0.34, 0.34 to 0.74, and -0.27, respectively, and with AFF were -0.11, -0.04 to -0.41, and 0.76, respectively. Days to 114 kg had genetic associations with Stay, AFF, and TNB of 0.52, -0.25, and -0.08, respectively. Backfat at 114 kg had genetic correlations with Stay, AFF, and TNB of -0.29, 0.14, and 0.47, respectively. Vulva redness and TNB were negatively correlated phenotypically (r = -0.14) and genetically (r = -0.53). Associations between structural conformation traits with Stay, AFF, TNB, and WCI were generally low to moderate and favorable. Selection for longer length of estrus, stronger standing reflex, or younger age at puberty would increase the proportion of gilts that farrow and reduce age at first farrowing.


Subject(s)
Body Composition , Estrus/genetics , Reproduction , Sus scrofa/genetics , Sus scrofa/physiology , Animals , Female , Puberty/genetics , Sexual Behavior, Animal , Sus scrofa/growth & development
14.
Br J Cancer ; 103(12): 1788-93, 2010 Dec 07.
Article in English | MEDLINE | ID: mdl-21081926

ABSTRACT

BACKGROUND: overexpression of HER-2 is observed in 15-25% of breast cancers, and is associated with increased risk of recurrence. Current guidelines recommend trastuzumab and chemotherapy for most HER-2-positive patients. However, the majority of patients does not recur and might thus be overtreated with adjuvant systemic therapy. We investigated whether the 70-gene MammaPrint signature identifies HER-2-positive patients with favourable outcome. METHODS: in all, 168 T1-3, N0-1, HER-2-positive patients were identified from a pooled database, classified by the 70-gene signature as good or poor prognosis, and correlated with long-term outcome. A total of 89 of these patients did not receive adjuvant chemotherapy. RESULTS: in the group of 89 chemotherapy-naive patients, after a median follow-up of 7.4 years, 35 (39%) distant recurrences and 29 (33%) breast cancer-specific deaths occurred. The 70-gene signature classified 20 (22%) patients as good prognosis, with 10-year distant disease-free survival (DDFS) of 84%, compared with 69 (78%) poor prognosis patients with 10-year DDFS of 55%. The estimated hazard ratios (HRs) were 4.5 (95% confidence interval (CI) 1.1-18.7, P=0.04) and 3.8 (95% CI 0.9-15.8, P=0.07) for DDFS and breast cancer-specific survival (BCSS), respectively. In multivariate analysis adjusted for known prognostic factors and hormonal therapy, HRs were 5.8 (95% CI 1.3-26.7, P=0.03) and 4.7 (95% CI 1.0-21.7, P=0.05) for DDFS and BCSS, respectively. INTERPRETATION: the 70-gene prognosis signature is an independent prognostic indicator that identifies a subgroup of HER-2-positive early breast cancer with a favourable long-term outcome.


Subject(s)
Breast Neoplasms/mortality , Gene Expression Profiling , Receptor, ErbB-2/analysis , Adult , Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Female , Humans , Middle Aged , Prognosis , Proportional Hazards Models
15.
J Anim Sci ; 88(11): 3486-92, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20675607

ABSTRACT

The purpose of this study was to determine the association of production factors with stayability to parity 4 (STAY4) under controlled experimental conditions. Data were from 2,293 female pigs, sampled from 6 genetic lines that were entered into the National Pork Producers Council Maternal Line National Genetic Evaluation Program. Genetic lines evaluated included Newsham (NH), National Swine Registry (NSR), American Diamond Swine Genetics (ADSG), Danbred (DAN), and 2 Dekalb-Monsanto lines (DK44 and GPK347). Stepwise logistic regression was utilized in the analysis of STAY4. All effects were nested within genetic line. Categorical effects in the model were arrival date to the wean-to-finish unit (entry date) and breed-gestation-farrowing facility (farm). Continuous effects in the model were gilt backfat, LM depth, ADG, age at puberty, age at first farrowing, and traits recorded before the last litter of the sow (prefarrow backfat, number born alive, number weaned, litter weaning weight, lactation feed intake, lactation backfat loss, and lactation length). Factors significant for STAY4 included farm, entry date, age at first farrowing, ADG, gilt backfat, and lactation before removal effects, as well as feed intake, number born alive, and lactation length. Age at first farrowing and lactation feed intake affected all genetic lines. Regression coefficients for STAY4 on age at first farrowing were -0.014, -0.022, -0.017, -0.016, -0.011, and -0.021 (all P < 0.05), respectively, for NH, NSR, ADSG, DK44, GPK347, and DAN genetic lines. Regression coefficients for STAY4 on lactation feed intake were 0.043, 0.049, 0.051, 0.061, 0.120, and 0.097 (all P < 0.05), respectively, for NH, NSR, ADSG, DK44, GPK347, and DAN females. Age at puberty, age at first farrowing, and lactation feed intake had the greatest effect on STAY4.


Subject(s)
Longevity/genetics , Swine/genetics , Swine/physiology , Adipose Tissue , Animals , Female , Fertility/genetics , Genetic Variation , Genotype , Reproduction/genetics
16.
J Anim Sci ; 88(9): 2913-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20525928

ABSTRACT

Variance components and genetic correlations were estimated among estrus, puberty, growth, and composition traits in Landrace-Large White gilts (n = 1,225; Genetic Improvement Services, Newton Grove, NC) from 59 sires and 330 dams. Four groups of gilts entered the North Carolina Swine Evaluation Station in Clayton at an average age of 162 d and were checked daily for estrus. Once 70% of gilts had reached puberty, recording of estrus symptoms occurred every 12 h for 30 d, using fence-line boar contact. Subjective estrus traits were maximum strength of standing reflex with or without a boar present, total strength of standing reflex with or without a boar present, and strength of vulva reddening and swelling. Objective estrus traits consisted of vulva redness, vulva width, length of estrus in consecutive days based on 12-h observations, and age at puberty (AGEPUB). Growth and composition traits included puberty weight, days to 114 kg (DYS), 10th-rib backfat, and 10th-rib LM area at 114 kg (BF, LMA) and puberty. Variance components were estimated using AIREMLF90 with an animal model. All models included gilt development diet class and breed composition as fixed effects, entry age as a covariate (except DYS, BF, and LMA), a random common litter effect, and a random animal genetic effect. Heritability estimates for length of estrus, maximum strength of the standing reflex with a boar, total strength of the standing reflex with a boar, maximum strength of the standing reflex without a boar, total strength of the standing reflex without a boar, vulva redness, strength of vulva reddening and swelling, and vulva width were 0.21, 0.13, 0.26, 0.42, 0.42, 0.26, 0.45, and 0.58, respectively. Heritability estimates for AGEPUB, puberty weight, 10th-rib backfat at puberty, 10th-rib LM area at puberty, DYS, BF, and LMA were 0.29, 0.39, 0.41, 0.38, 0.24, 0.47, and 0.39, respectfully. Common litter effect estimates ranged from 0.01 to 0.09. The estimated genetic correlation between length of estrus and maximum strength of standing reflex with a boar was 0.99. Genetic correlations between AGEPUB and length of estrus, maximum strength of standing reflex with a boar, and vulva redness were -0.23, -0.32, and 0.20, respectively. Length of estrus had positive genetic associations with DYS and BF (0.30 and 0.29, respectively). It was concluded that past selection for lean BW gain may have weakened the strength of the standing reflex and that sufficient genetic variation exists to make selection for improved swine estrus traits effective.


Subject(s)
Estrus/genetics , Swine/genetics , Swine/physiology , Animals , Female , Male , Sexual Behavior, Animal/physiology , Sexual Maturation/genetics , Vulva/physiology
17.
Eur J Surg Oncol ; 35(8): 798-804, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19013747

ABSTRACT

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is equivalent to adjuvant therapy (AdC) in terms of survival and disease-free interval. Many institutions add AdC after NAC and surgery. However, such extended chemotherapy (ExC) is not evidence based. Study aim was to investigate if ExC improved disease-free (DFS) and overall survival (OS). PATIENTS AND METHODS: From 1998 to 2006 356 consecutive patients received NAC (45 pts), AdC (221 pts) or ExC (90 pts). We analysed these 3 groups to determine effects of ExC and to identify patients who might benefit. NAC consisted in 93% of 3-6 cycles of epirubicin+docetaxel, AdC comprised EC+/-taxanes in 72%. Median age in the NAC, AdC, and ExC-groups was 54, 56 and 52 years with follow-up of 30, 57, and 55 months. RESULTS: After NAC, 35% achieved downstaging and 10% pathologic complete remission. Surprisingly ExC seemed to result in reduction of 5-year DFS: compared to 85% and 82% after NAC and AdC, DFS was 61% after ExC (p=0.001). OS was not significantly affected (79, 91, and 78% after NAC, AdC and ExC, p=0.13). In multivariate analysis after correction for age, menopausal status, stage, grading, hormone receptors, her2-status, radiotherapy and surgery, ExC seemed to adversely affect DFS (HR 2.15, p=0.008), loco-regional and distant recurrence-rates (HR 3.0, p=0.03 and HR 2.0, p=0.02). DISCUSSION: In this single-center analysis ExC could not show advantages in terms of DFS and OS. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials. Until then, extended chemotherapy should be considered carefully. As in previous studies, no differences were found between NAC and AdC groups.


Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Female , Humans , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Survival Analysis
18.
Prev Vet Med ; 82(3-4): 198-212, 2007 Dec 14.
Article in English | MEDLINE | ID: mdl-17604857

ABSTRACT

Physical and reproductive conditions of cull sows (3158) from two U.S. Midwestern harvest plants were assessed. Body condition, feet, shoulders, teeth, lungs, and reproductive tracts were visually evaluated for gross lesions on harvested sows. PROC FREQ (SAS, Cary, NC) was used to calculate the frequency of each binary trait event. Pearson chi-square tests were used to test the alternative hypothesis that a linear association existed between binary traits and body condition score (BCS). The most common foot lesions observed were rear (n=2064, 67.5%) and front (n=1024, 32.9%) heel lesions. Cracked hooves were found on the front feet of 703 (22.6%) and rear feet of 552 (18.1%) sows. Rear digital overgrowth was observed in 644 (21.1%) sows. The most common reproductive gross lesion observed among harvested cull sows was acyclic ovaries (n=277, 9.0%). Presence of acyclic ovaries increased (p<0.01) as BCS decreased. Cystic ovaries were found in 192 (6.3%) sows, which increased (p<0.01) as BCS increased. Pneumonia was observed in 298 (9.7%) sows, and increased in frequency as BCS decreased (p<0.01). The most frequently observed shoulder lesion among harvested cull sows was shoulder abrasions (n=394, 12.5%). The presence of shoulder abrasions increased (p<0.01) as BCS decreased. The prevalence of reproductive lesions detected in the present study was less than the reported percentage of sows culled for reproductive failure from previous studies based on record keeping summaries.


Subject(s)
Swine Diseases/pathology , Abattoirs , Animals , Body Composition , Female , Foot Diseases/pathology , Foot Diseases/veterinary , Genital Diseases, Female/pathology , Genital Diseases, Female/veterinary , Hoof and Claw/pathology , Midwestern United States , Pregnancy , Skin Diseases/pathology , Skin Diseases/veterinary , Swine , Tooth Diseases/pathology , Tooth Diseases/veterinary
19.
Eur J Surg Oncol ; 32(10): 1180-5, 2006 Dec.
Article in English | MEDLINE | ID: mdl-16750344

ABSTRACT

AIMS: In patients with early breast cancer sentinel node biopsy (SNB) proved to be an accurate procedure for axillary staging with significantly reduced morbidity. Medium- and long-term observational studies are needed to establish, whether SNB alone is able to prevent locoregional recurrence without impairing long-term survival. METHODS: 298 patients with invasive breast cancer were subjected to SNB in a prospective audit. Lymphatic mapping was performed with blue dye and radiocolloids. 180 patients had SNB alone (group 1), while 118 subsequently underwent axillary dissection (AD; group 2). In ten patients AD was omitted despite the tumor burden in the SN. Clinical follow-up studies were performed at regular intervals. The mean follow-up time was 47months in group 1 (range 7-90) and 46months in group two (range 1-87months). RESULTS: Sentinel nodes were identified in 286 out of 298 patients (96%). One patient in group 1 developed axillary and simultaneous supraclavicular lymph node recurrence. After AD regional relapses have so far not been observed. One ipsilateral local recurrence was detected in each group. Five patients in group 1 and 15 patients in group 2 developed distant metastases. Three out of six and eight out of nine patients, respectively, died of their advanced disease. All patients with SN tumor infiltration not subjected to AD are alive and well. CONCLUSIONS: Axillary recurrence is rare after sentinel node biopsy alone. Its rate is comparable to that after AD, even in patients with SN micrometastases. These conclusions are confirmed by reports in the literature.


Subject(s)
Breast Neoplasms/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/therapy , Combined Modality Therapy , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Middle Aged , Neoplasm Recurrence, Local
20.
Anaesthesist ; 55(1): 41-4, 2006 Jan.
Article in German | MEDLINE | ID: mdl-16228150

ABSTRACT

Life-threatening incidents during leisure sport activities are not uncommon and also cardiovascular problems are occurring with ever-increasing frequency during alpine downhill skiing. Because these are emergency situations which regularly occur in distant or at least not easily accessible areas, assistance from lay persons can be the decisive factor for survival. The report describes a case of cardiopulmonary resuscitation of a skier in alpine terrain, who survived a cessation of circulation without sequelae after rapid defibrillation by maintenance personnel. A review of possibilities for improved emergency medical care in mountainous regions is also given.


Subject(s)
Cardiopulmonary Resuscitation , Electric Countershock , Skiing , Electrocardiography , Emergency Medical Services , Heart Arrest/therapy , Humans , Hypercholesterolemia/complications , Male , Middle Aged , Smoking/physiopathology , Survival
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