The genomic expression test EndoPredict is a prognostic tool for identifying risk of local recurrence in postmenopausal endocrine receptor-positive, her2neu-negative breast cancer patients randomised within the prospective ABCSG 8 trial.
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ABSTRACT:
SUBMITTER: Fitzal F
PROVIDER: S-EPMC4402462 | biostudies-other | 2015 Apr
REPOSITORIES: biostudies-other
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Project description:In a patient with multiple endocrine neoplasia type 2A (MEN2A), an inverted physiological ratio between urinary normetanephrines and metanephrines is an early marker of recurrence in epinephrine-secreting pheochromocytoma, and 131I MIBG treatment appears to be a useful therapeutic option in order to avoid multiple invasive surgical procedures in pheochromocytomatosis.
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Project description:Bacteria cooperate by working collaboratively to defend their colonies, share nutrients, and resist antibiotics. Nevertheless, our understanding of these remarkable behaviours primarily comes from studying a few well-characterized species. Consequently, there is a significant gap in our understanding of microbial social traits, particularly in natural environments. To address this gap, we can use bioinformatic tools to identify genes that control cooperative or otherwise social traits. Existing tools address this challenge through two approaches. One approach is to identify genes that encode extracellular proteins, which can provide benefits to neighbouring cells. An alternative approach is to predict gene function using annotation tools. However, these tools have several limitations. Not all extracellular proteins are cooperative, and not all cooperative behaviours are controlled by extracellular proteins. Furthermore, existing functional annotation methods frequently miss known cooperative genes. We introduce SOCfinder as a new tool to find bacterial genes that control cooperative or otherwise social traits. SOCfinder combines information from several methods, considering if a gene is likely to [1] code for an extracellular protein [2], have a cooperative functional annotation, or [3] be part of the biosynthesis of a cooperative secondary metabolite. We use data on two extensively-studied species (P. aeruginosa and B. subtilis) to show that SOCfinder is better at finding known cooperative genes than existing tools. We also use theory from population genetics to identify a signature of kin selection in SOCfinder cooperative genes, which is lacking in genes identified by existing tools. SOCfinder opens up a number of exciting directions for future research, and is available to download from https://github.com/lauriebelch/SOCfinder.
| S-EPMC10763506 | biostudies-literature
Project description:IntroductionPatients with early-stage breast cancer, treated with endocrine therapy, have approximately 90% 5-year disease-free survival. However, for patients at higher risk of relapse despite endocrine therapy, additional adjuvant therapy, such as chemotherapy, may be indicated. The challenge is to prospectively identify such patients. The Mammostrat® test uses five immunohistochemical markers to stratify patients on tamoxifen therapy into risk groups to inform treatment decisions. We tested the efficacy of this panel in a mixed population of cases treated in a single center with breast-conserving surgery and long-term follow-up.MethodsTissue microarrays from a consecutive series (1981 to 1998) of 1,812 women managed by wide local excision and postoperative radiotherapy were collected following appropriate ethical review. Of 1,390 cases stained, 197 received no adjuvant hormonal or chemotherapy, 1,044 received tamoxifen only, and 149 received a combination of hormonal therapy and chemotherapy. Median age at diagnosis was 57, 71% were postmenopausal, 23.9% were node-positive and median tumor size was 1.5 cm. Samples were stained using triplicate 0.6 mm2 tissue microarray cores, and positivity for p53, HTF9C, CEACAM5, NDRG1 and SLC7A5 was assessed. Each case was assigned a Mammostrat risk score, and distant recurrence-free survival (DRFS), relapse-free survival (RFS) and overall survival (OS) were analyzed by marker positivity and risk score.ResultsIncreased Mammostrat scores were significantly associated with reduced DRFS, RFS and OS in estrogen receptor (ER)-positive breast cancer (P < 0.00001). In multivariate analyses the risk score was independent of conventional risk factors for DRFS, RFS and OS (P < 0.05). In node-negative, tamoxifen-treated patients, 10-year recurrence rates were 7.6 ± 1.5% in the low-risk group versus 20.0 ± 4.4% in the high-risk group. Further, exploratory analyses revealed associations with outcome in both ER-negative and untreated patients.ConclusionsThis is the fifth independent study providing evidence that Mammostrat can act as an independent prognostic tool for ER-positive, tamoxifen-treated breast cancer. In addition, this study revealed for the first time a possible association with outcome regardless of node status and ER-negative tumors. When viewed in the context of previous results, these data provide further support for this antibody panel as an aid to patient management in early-stage breast cancer.
| S-EPMC2949634 | biostudies-literature
Project description:Unlabelled: We present Goldilocks: a Python package providing functionality for collecting summary statistics, identifying shifts in variation, discovering outlier regions and locating and extracting interesting regions from one or more arbitrary genomes for further analysis, for a user-provided definition of interesting.Availability and implementationGoldilocks is freely available open-source software distributed under the MIT licence. Source code is hosted publicly at https://github.com/SamStudio8/goldilocks and the package may also be installed using pip install goldilocks. Documentation can be found at https://goldilocks.readthedocs.orgContact: msn@aber.ac.ukSupplementary informationSupplementary data are available at Bioinformatics online.
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Project description:IntroductionOsteosarcoma is a high-morbidity bone cancer with an unsatisfactory prognosis. The aim of this study is to develop novel potential prognostic biomarkers and construct a prognostic risk prediction model for recurrence in osteosarcoma.MethodsBy analyzing microarray data, univariate and multivariate Cox regression analyses were performed to screen prognostic RNA signatures and to build a prognostic model. The RNA signatures were validated using Kaplan-Meier curves. Then, we developed and validated a nomogram combining age, recurrence, metastatic, and Prognostic score (PS) models to predict the individual's overall survival at the 3- and 5-year points. Pathway enrichment of RNA was conducted based on the significant co-expressed RNAs.ResultsA total of 319 mRNAs and 14 lncRNAs were identified in the microarray data. One lncRNA (LINC00957) and six mRNAs (METL1, CA9, B3GALT4, ALDH1A1, LAMB3, and ITGB4) were identified as RNA signatures and showed good performances in survival prediction for both the training and validation cohorts. Cox regression analysis showed that the seven RNA signatures could independently predict overall survival. Furthermore, age, recurrence, metastatic, and PS models were identified as independent prognostic factors via univariate and multivariate Cox analyses (P < 0.05) and included in the prognostic nomogram. The C-index values for the 3- and 5-year overall survival predictions of the nomogram were 0.809 and 0.740, respectively.ConclusionsThe current study provides the novel potential of seven RNA candidates as prognostic biomarkers. Nomograms were constructed to provide accurate and individualized survival prediction for recurrence in osteosarcoma patients.
| S-EPMC7758551 | biostudies-literature
Project description:ObjectiveOur objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement.EvidenceEach expert conducted extensive literature searches of case control, cohort, and randomized controlled trials as well as meta-analyses, Cochrane reviews, and Position Statements from other professional societies in order to compile and evaluate available evidence. No unpublished data were used to draw conclusions from the evidence.Consensus processA consensus was reached after several iterations. Each topic was considered separately, and a consensus was achieved as to content to be included and conclusions reached between the primary author and the peer reviewer specific to that topic. In a separate iteration, the quality of evidence was judged using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system in common use by The Endocrine Society for preparing clinical guidelines. The final iteration involved responses to four levels of additional review: 1) general comments offered by each of the 25 authors; 2) comments of the individual Task Force members; 3) critiques by the reviewers of the Journal of Clinical Endocrinology & Metabolism; and 4) suggestions offered by the Council and members of The Endocrine Society. The lead author compiled each individual topic into a coherent document and finalized the content for the final Statement. The writing process was analogous to preparation of a multiauthored textbook with input from individual authors and the textbook editors.ConclusionsThe major conclusions related to the overall benefits and risks of MHT expressed as the number of women per 1000 taking MHT for 5 yr who would experience benefit or harm. Primary areas of benefit included relief of hot flashes and symptoms of urogenital atrophy and prevention of fractures and diabetes. Risks included venothrombotic episodes, stroke, and cholecystitis. In the subgroup of women starting MHT between ages 50 and 59 or less than 10 yr after onset of menopause, congruent trends suggested additional benefit including reduction of overall mortality and coronary artery disease. In this subgroup, estrogen plus some progestogens increased the risk of breast cancer, whereas estrogen alone did not. Beneficial effects on colorectal and endometrial cancer and harmful effects on ovarian cancer occurred but affected only a small number of women. Data from the various Women's Health Initiative studies, which involved women of average age 63, cannot be appropriately applied to calculate risks and benefits of MHT in women starting shortly after menopause. At the present time, assessments of benefit and risk in these younger women are based on lower levels of evidence.
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Project description:We studied the association between mammographic calcifications and local recurrence in the ipsilateral breast.Case-cohort study within a randomised trial of radiotherapy in breast conservation for ductal cancer in situ of the breast (SweDCIS). We studied mammograms from cases with an ipsilateral breast event (IBE) and from a subcohort randomly sampled at baseline. Lesions were classified as a density without calcifications, architectural distortion, powdery, crushed stone-like or casting-type calcifications.Calcifications representing necrosis were found predominantly in younger women. Women with crushed stone or casting-type microcalcifications had higher histopathological grade and more extensive disease. The relative risk (RR) of a new IBE comparing those with casting-type calcifications to those without calcifications was 2.10 (95% confidence interval (CI) 0.92-4.80). This risk was confined to in situ recurrences; the RR of an IBE associated with casting-type calcifications on the mammogram adjusted for age and disease extent was 16.4 (95% CI 2.20-140).Mammographic appearance of ductal carcinoma in situ of the breast is prognostic for the risk of an in situ IBE and may also be an indicator of responsiveness to RT in younger women.
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Project description:The preoperative endocrine prognostic index (PEPI) predicts survival after neoadjuvant endocrine therapy (NAE) using aromatase inhibitors (AIs) for women with postmenopausal estrogen receptor (ER)-positive breast cancer irrespective of the human epidermal growth factor receptor 2 (HER2) status. Although the progesterone receptor (PgR) is also a prognostic factor for ER-positive breast cancer, the PgR status was not considered a prognostic factor in the original PEPI scoring system. In this study, we investigated the utility of a modified PEPI including the PgR status (PEPI-P) as a prognostic factor after NAE for postmenopausal patients with ER-positive and HER2-negative breast cancer. We enrolled 107 patients with invasive ER-positive and HER2-negative breast cancer treated with exemestane for ≥4 months as NAE. We initially assessed PEPI and compared survival between the groups. Additionally, we obtained an effective cutoff for PgR through survival analysis. Then, we assessed the survival significance of PEPI-P. A PgR staining rate of 50% was the most significant cutoff for predicting recurrence-free survival (RFS) and cancer-specific survival (CSS). PEPI was a significant prognostic factor; moreover, PEPI-P was the most significant prognostic indicator for RFS and CSS. PEPI-P is a potent prognostic indicator of survival after NAE using AIs for postmenopausal patients with ER-positive and HER2-negative breast cancer. This modified PEPI may be useful for therapeutic decision-making regarding postmenopausal ER-positive and HER2-negative breast cancer after NAE.
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Project description:Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age < 50 years, tumor size, luminal B (HER2-) subtype and breast-conserving therapy were additional risk factors for local recurrence. Compared to the luminal A subtype, the risk of systemic recurrence was higher for all other subtypes; additional risk factors for systemic recurrence were lymphatic invasion, absence of systemic therapy and mastectomy. Conclusion: Overall, the risk of local and loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.
| S-EPMC4520963 | biostudies-literature
Project description:BackgroundPreoperative and perioperative aromatase inhibitor (POAI) therapy has the potential to improve outcomes in women with operable oestrogen receptor-positive primary breast cancer. It has also been suggested that tumour Ki67 values after 2 weeks (Ki672W) of POAI predicts individual patient outcome better than baseline Ki67 (Ki67B). The POETIC trial aimed to test these two hypotheses.MethodsPOETIC was an open-label, multicentre, parallel-group, randomised, phase 3 trial (done in 130 UK hospitals) in which postmenopausal women aged at least 50 years with WHO performance status 0-1 and hormone receptor-positive, operable breast cancer were randomly assigned (2:1) to POAI (letrozole 2·5 mg per day orally or anastrozole 1 mg per day orally) for 14 days before and following surgery or no POAI (control). Adjuvant treatment was given as per UK standard local practice. Randomisation was done centrally by computer-generated permuted block method (variable block size of six or nine) and was stratified by hospital. Treatment allocation was not masked. The primary endpoint was time to recurrence. A key second objective explored association between Ki67 (dichotomised at 10%) and disease outcomes. The primary analysis for clinical endpoints was by modified intention to treat (excluding patients who withdrew consent). For Ki67 biomarker association and endpoint analysis, the evaluable population included all randomly assigned patients who had paired Ki67 values available. This study is registered with ClinicalTrials.gov, NCT02338310; the European Clinical Trials database, EudraCT2007-003877-21; and the ISRCTN registry, ISRCTN63882543. Recruitment is complete and long-term follow-up is ongoing.FindingsBetween Oct 13, 2008, and April 16, 2014, 4480 women were recruited and randomly assigned to POAI (n=2976) or control (n=1504). On Feb 6, 2018, median follow-up was 62·9 months (IQR 58·1-74·1). 434 (10%) of 4480 women had a breast cancer recurrence (280 [9%] POAI; 154 [10%] control), hazard ratio 0·92 (95% CI 0·75-1·12); p=0·40 with the proportion free from breast cancer recurrence at 5 years of 91·0% (95% CI 89·9-92·0) for patients in the POAI group and 90·4% (88·7-91·9) in the control group. Within the POAI-treated HER2-negative subpopulation, 5-year recurrence risk in women with low Ki67B and Ki672W (low-low) was 4·3% (95% CI 2·9-6·3), 8·4% (6·8-10·5) with high Ki67B and low Ki672W (high-low) and 21·5% (17·1-27·0) with high Ki67B and Ki672W (high-high). Within the POAI-treated HER2-positive subpopulation, 5-year recurrence risk in the low-low group was 10·1% (95% CI 3·2-31·3), 7·7% (3·4-17·5) in the high-low group, and 15·7% (10·1-24·4) in the high-high group. The most commonly reported grade 3 adverse events were hot flushes (20 [1%] of 2801 patients in the POAI group vs six [<1%] of 1400 in the control group) and musculoskeletal pain (29 [1%] vs 13 [1%]). No treatment-related deaths were reported.InterpretationPOAI has not been shown to improve treatment outcome, but can be used without detriment to help select appropriate adjuvant therapy based on tumour Ki67. Most patients with low Ki67B or low POAI-induced Ki672W do well with adjuvant standard endocrine therapy (giving consideration to clinical-pathological factors), whereas those whose POAI-induced Ki672W remains high might benefit from further adjuvant treatment or trials of new therapies.FundingCancer Research UK.
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