21,561 research outputs found
BRCA-deficient subtype signature identifies triple negative breast cancer patients with improved survival with anthracycline/taxane chemotherapy.
No full text(A) Proportion of BRCA-D tumors among TNBC tumors in different CMB categories. (B) Overall survival of TNBC patients by BRCA deficiency status in the TCGA cohort. (C) Overall survival of TNBC patients in the TCGA cohort by predicted BRCA deficiency status using the developed gene signature (high corresponds to BRCA-D; low to BRCA-N). (D) Overall survival of TNBC patients in the METABRIC cohort by predicted BRCA deficiency status using the developed gene signature (high corresponds to BRCA-D; low to BRCA-N). p-Values are from the log-rank test. BRCA-D, BRCA-deficient; BRCA-N, BRCA-normal; CMB, clonal mutation burden; TCGA, The Cancer Genome Atlas; TNBC, triple negative breast cancer.</p
BRCA-associated pancreatico-biliary neoplasms: Four cases illustrating the emerging clinical impact of genotyping
No full textBRCA-associated pancreatico-biliary neoplasms: Four cases illustrating the emerging clinical impact of genotypin
Management of the asymptomatic BRCA mutation carrier
No full textPaige Teller1, Rita K Kramer21Surgical Oncology, 2Medical Oncology, Medical University of South Carolina, Charleston, SC, USAAbstract: Current management of an asymptomatic BRCA mutation carrier includes early initiation and intensive cancer screening in combination with risk reduction strategies. The primary objectives of these interventions are earlier detection and cancer prevention to increase quality of life and prolonged survival. Existing recommendations are often based on the consensus of experts as there are few, supportive, randomized control trials. Management strategies for unaffected patients with BRCA mutations are continually redefined and customized as more evidence-based knowledge is acquired with regard to current intervention efficacy, mutation-related histology, and new treatment modalities. This review provides an outline of current, supported management principles, and interventions in the care of the asymptomatic BRCA mutation carrier. Topics covered include surveillance modalities and risk reduction achieved through behavioral modification, chemoprevention, and prophylactic surgery.Keywords: high risk, screening, risk reduction, hereditary breast cancer syndrom
Fertility in BRCA mutation carriers: counseling BRCA-mutated patients on reproductive issues.
No full textObjectives Genetic testing rates for hereditary breast and ovarian cancer (HBOC) have steadily increased during the past decades resulting in a growing population of young and healthy mutation carriers. Available data on fertility issues in BRCA mutation carriers is rising but the results remain to some extent still conflicting. We have performed a systematic literature review in order to get an overview concerning the current evidence on fertility issues in BRCA mutation carriers. Data were analyzed critically with the aim to deliver physicians a solid basis for (onco) fertility counseling in women with BRCA mutations. Content We present the latest data on cancer risks in women with HBOC and analyze the influence of cancer treatment and preventive surgery on the reproductive potential. Epidemiological studies on fertility issues in BRCA mutation carriers showed heterogeneous results. However, several authors showed a decreased ovarian reserve with lower Anti-Müllerien hormone (AMH) levels and poorer response to ovarian stimulation in BRCA positive women. The diagnosis of BRCA mutations influences reproductive decision-making. Additionally, the shortened reproductive window and the need to complete family planning early has a significant psychological impact. Summary and Outlook This article highlights the importance of fertility counseling in BRCA mutation carriers. Individual fertility counseling is mandatory. Fertility preservation strategies should be discussed
Bcr/Abl Interferes with the Fanconi Anemia/BRCA Pathway: Implications in the Chromosomal Instability of Chronic Myeloid Leukemia Cells
No full textChronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. Although it is well known that CML cells are genetically unstable, the mechanisms accounting for this genomic instability are still poorly understood. Because the Fanconi anemia (FA) pathway is believed to control several mechanisms of DNA repair, we investigated whether this pathway was disrupted in CML cells. Our data show that CML cells have a defective capacity to generate FANCD2 nuclear foci, either in dividing cells or after DNA damage. Similarly, human cord blood CD34(+) cells transduced with BCR/ABL retroviral vectors showed impaired FANCD2 foci formation, whereas FANCD2 monoubiquitination in these cells was unaffected. Soon after the transduction of CD34+ cells with BCR/ABL retroviral vectors a high proportion of cells with supernumerary centrosomes was observed. Similarly, BCR/ABL induced a high proportion of chromosomal abnormalities, while mediated a cell survival advantage after exposure to DNA cross-linking agents. Significantly, both the impaired formation of FANCD2 nuclear foci, and also the predisposition of BCR/ABL cells to develop centrosomal and chromosomal aberrations were reverted by the ectopic expression of BRCA1. Taken together, our data show for the first time a disruption of the FA/BRCA pathway in BCR/ABL cells, suggesting that this defective pathway should play an important role in the genomic instability of CML by the co-occurrence of centrosomal amplification and DNA repair deficiencies
2D-shear wave elastography : number of acquisitions can be reduced according to clinical setting
No full textAbstract: BACKGROUND The factors affecting intra-operator variability of two-dimensional shear wave elastography (2D-SWE) have not been clearly established. We evaluated 2D-SWE variability according to the number of measurements, clinical and laboratory features, and liver stiffness measurements (LSM). METHODS At least three LSM were performed in 452 patients who underwent LSM by 2D-SWE (supersonic shear imaging) out of an initial database of 1650 patients. The mean value of the three LSM was our best measurement method. Bland-Altman plots were used to evaluate intra-operator variability when considering only one, or the first two measurements. Variability was assessed by taking the absolute value of the difference between the first LSM and the mean of the three LSM. Logistic regression was used to assess the factors associated with the highest tertile of variability. RESULTS The limit of agreement was narrower with the mean of the first and second measurements than with each measurement taken separately (-\u20092.83 to 2.99\ua0kPa vs. -\u20095.86 to 6.21\ua0kPa and -\u20095.77 to 5.73\ua0kPa for the first and second measurement, respectively). A BMI\u2009 65\u200925\ua0kg/m2 and a first LSM by 2D-SWE\u2009 65\u20097.1\ua0kPa increased the odds of higher variability by 3.4 and 3.9, respectively. Adding a second LSM didn't change the variability in patients with BMI\u2009<\u200925 and a first LSM by 2D-SWE\u2009<\u20097.1\ua0kPa. CONCLUSIONS Intra-operator variability of LSM by 2D-SWE increases with both a high BMI and high LSM value. In patients with BMI\u2009<\u200925\ua0kg/m2 and a first LSM\u2009<\u20097.1\ua0kPa we recommend performing only one LSM
The Pontoon Project / Skissuppdrag / initial concept for public art project Nya Slussen, Stockholm (SWE)
No full textConcept for a different role for durational participatory visual art in relation to mega scale urban re-organisation projects, using a commission from Stockholm Konst (SWE) regarding Nya Slussen in Stockholm city centre, as a case. Elaborated by Kerstin Bergendal, in collaboration with Andrea Philips (UK), SLA Stig L Andersson (DK) and Johanna Adebäck (SWE)
BRCA-EU mutation signature analysis.
No full texta SNV mutation signatures. SNVs are organized according to the SNV type (color). Within each type, SNVs are further organized into the pattern of flanking nucleotides (A—A, A—C, …,T—G, T—T). b SV mutation signatures. SVs are grouped by type (DEL: deletion, DUP: tandem duplication, INV: inversion, TR: translocation). c Heatmap of relative signature probabilities in BRCA-EU samples. Each heatmap column represents a single sample, and is composed of the SNV and SV signature probabilities output from the MMCTM model. The values for each signature (row) have been standardized, producing z-scores. Heatmap display has been truncated to ±3. Samples have been hierarchically clustered according to their transformed signature probabilities and cluster labels are indicated with colors underneath the dendrogram. The number of samples in each cluster is indicated in parentheses in the cluster legend. ER, PR, and HER2 positive status, BRCA1/2 mutation or methylation status, other gene driver mutation status, HRDetect prediction, and MMRD status is indicated with black bars. Grey cells represent missing data for annotation tracks. Samples with zero mutations for a mutation type also have grey signature probability cells. d Correlation heatmap between SNV and SV signatures. e Annotation associations for sample clusters. Upward- and downward-pointing triangles indicate enrichment and depletion, respectively. Adjusted p-values >0.05 are not shown. Colors correspond to cluster colors indicated in the heatmap.</p
Surgical menopause in BRCA-mutated women: metabolic aspects and impact on the quality of life
No full textopenRIASSUNTO
Presupposti dello studio
La scoperta della mutazione dei geni BRCA 1 e BRCA 2, correlata a soprattutto al
cancro della mammella e dell’ovaio, ha reso necessaria l’individuazione di percorsi
terapeutici dedicati per le pazienti.
Per quanto riguarda il tumore ovarico legato a BRCA1 o BRCA2, è stata consigliata
una sorveglianza semestrale, e a partire dai 35 anni di età per il BRCA1 e i 40 anni
di età per il BRCA2, è consigliata l’annessiectomia bilaterale profilattica.
L’annessiectomia bilaterale profilattica è un ottimo strumento preventivo,
abbattendo più del 80-96% il rischio di tumore ovarico, ma non è esente da
complicanze.
Comporta infatti una menopausa chirurgica precoce che può avere importanti
effetti sulla qualità di vita.
Obiettivi dello studio
Valutare gli effetti della menopausa iatrogena dovuta alla annessiectomia
profilattica, analizzandone i segni e i sintomi.
Materiali e metodi
Sono state selezionati le pazienti portatrici di mutazione BRCA1 o BRCA2 di età
inferiore o uguale a 50 anni, sottoposte tra l’anno 2007 e l’anno 2022 ad
annessiectomia profilattica e in follow-up presso la Clinica Ginecologica Azienda
Ospedale Università di Padova e/o l’Ambulatorio Tumori Ereditari dell’Istituto
Oncologico Veneto.
Della menopausa chirurgica sono stati valutati i dati relativi agli aspetti metabolici:
densità ossea, ipercolesterolemia, pressione arteriosa, glicemia a digiuno; si sono
indagati i sintomi soggettivi legati alla menopausa.
Infine, si è valutato l’utilizzo della terapia ormonale sostitutiva.
Risultati
40.5% delle pazienti lamentava sintomi vasomotori, 21.6% disturbi della memoria,
23% disturbi dell’umore, 5.4% una sensazione di offuscamento della memoria e
25.7% presentava sindrome genitourinaria.
Per quanto riguarda la diminuzione di densità ossea, 29 (39.2%) delle pazienti
presentava osteopenia e 12 (16.2%) osteoporosi.
Inoltre, solo 8% delle pazienti utilizzava la TOS dall’inizio.
Conclusioni
I sintomi correlati alla menopausa chirurgica si sono dimostrati inficiare in maniera
importante la qualità di vita e il metabolismo osseo delle pazienti sottoposte ad
annessiectomia bilaterale profilattica.
La TOS se eseguita nell’immediato post-chirurgico, in pazienti che non
presentavano controindicazioni alla stessa, si è rivelata più utile nel gestire e
migliorare i sintomi soggettivi e della salute ossea rispetto a non utilizzarla o
all’utilizzarla dopo lo sviluppo dei sintomi stessi.
Dunque, affiancare al follow-up oncologico la terapia ormonale sostitutiva,
potrebbe essere un modo per migliorare la qualità di vita per queste pazientiBackground
BRCA genes are associated to a higher risk of developing breast and ovarian
cancer.
Therefore, it is important to identify and screen women affected by a pathological
variant of these genes.
For ovarian cancer linked to BRCA1 or BRCA2, it’s suggested a screening every six
months, and risk reducing prophylactic bilateral oophorectomy is recommended
from the age of 35 for BRCA1 and 40 for BRCA2,
Prophylactic bilateral oophorectomy is an excellent preventive tool, reducing the
risk of ovarian cancer by 80-96%, but it leads to some complications.
In fact, it involves an early surgical menopause which can have effects on the
quality of life.
Aim
To evaluate the effects of surgical menopause due to prophylactic oophorectomy,
analyzing its consequences on the quality of life.
Materials and methods
The chosen population included patients 50 years old or younger, carrying BRCA
mutations, who underwent prophylactic adnexectomy between 2007 and 2022
and were undergoing a follow-up at the Clinica Ginecologica Azienda Ospedale
Università di Padova and/or at the Ambulatorio Tumori Ereditari of Istituto
Oncologico Veneto.
The data relating to the metabolic aspects of surgical menopause were evaluated:
bone density, hypercholesterolemia, blood pressure, fasting blood sugar; the
subjective symptoms related to menopause were investigated.
Finally, the use of hormone replacement therapy was evaluated.
Results
40.5% of the patients complained of vasomotor symptoms, 21.6% insomnia, 23%
mood disturbances, 5.4% a feeling of “mind fog” and 25.7% presented with
genitourinary syndrome.
Moreover, 29 (39.2%) of the patients was experiencing osteopenia and 12 (16.2%)
was suffering from osteoporosis.
Furthermore, only 8% of patients were using HRT from the start.
Conclusions
Symptoms related to surgical menopause often affect the quality of life of patients
undergoing prophylactic bilateral oophorectomy.
The use of HRT was shown to be more effective if started immediately after the
surgery, bettering the subjective symptoms and the bone health.
Therefore, using the HRT together with the oncological follow-up, might better the
quality of life of patients undergoing RRSBO in pre-menopausal period
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