Real-World Concordance between Germline and Tumour <i>BRCA1/2</i> Status in Epithelial Ovarian Cancer

Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour BRCA1/ 2 testing followed by germline BRCA1/2 testing in patients with a positive tumour test result. This testing model relies on tumour BRCA1/ 2 tests being able to detect all types of pathogenic variant. We analysed germline and tumour BRCA1/2 test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre. Tumour BRCA1/2 testing was performed using the next-generation sequencing (NGS)-based myChoice ® companion diagnostic (CDx; Myriad Genetics, Inc.). Germline BRCA1/2 testing was performed in the North West Genomic Laboratory Hub using NGS and multiplex ligation-dependent probe amplification. Between 11 April 2021 and 11 October 2023, 382 patients were successfully tested for tumour BRCA1 and BRCA2 variants. Of these, 367 (96.1%) patients were tested for germline BRCA1/ 2 variants. In those patients who underwent tumour and germline testing, 15.3% (56/367) had a BRCA1/ 2 pathogenic variant (36 germline and 20 somatic). All germline BRCA1/2 pathogenic small sequencing variants were detected in tumour DNA. By contrast, 3 out of 8 germline BRCA1/2 pathogenic large rearrangements were not reported in tumour DNA. The overall concordance of germline BRCA1/2 pathogenic variants detected in germline and tumour DNA was clinically acceptable at 91.7% (33/36). The myChoice ® CDx was able to detect most germline BRCA1/2 pathogenic variants in tumour DNA, although a proportion of pathogenic large rearrangements were not reported. If Myriad's myChoice ® CDx is used for tumour BRCA1/2 testing, our data supports a testing strategy of germline and tumour BRCA1/2 testing in all patients diagnosed with epithelial ovarian cancer aged &lt; 79 years old, with germline BRCA1/2 testing only necessary for patients aged ≥ 80 years old with a tumour BRCA1/2 pathogenic variant. </p

The Effect of Some Physical Factors and Lead on Soil and Smoking Workers in Gas Stations in Kirkuk Governorate

This study was completed in the city of Kirkuk. Environmental pollution with lead was studied in a number of government gas stations in Kirkuk Governorate, causing an increase in the rates of pollutants coming out of car exhaust, including the lead element in five sites, namely: Andalusia gas station, Al-Mutawra gas station, Baba Gurgur gas station, and Uqba bin Nafi gas station. The fifth site is the control site in the Domiz area in the south of the province. The research sampled the soil of these stations for a period of six months, a sample every month, starting from November 2022 until April 2023, and blood samples were taken for some smoking workers in those stations, as the concentration of the lead element in those samples was determined. Also, its effect on some blood parameters (C-RP, Pb) and pollution was studied by calculating the concentration of lead and some tests for the blood of people working in gas stations and those not working in them. The results of the study were determined by three main parts: First: Quantitative results related to the amount of lead present in the soil for filling stations and control area. Second: Quantitative results of some physical factors of the soil of filling stations. Third: Physiological results of some blood tests for some workers in the stations of smokers and control group. The quantitative results showed significant differences between the stations and the control area, as the results recorded the highest average concentration of lead in the soil (20.85 ± 0.35) ppm in the fourth station (Uqba bin Nafi) and the lowest average concentration (15.75 ± 0.34) ppm in the&nbsp; first station (Andalusia) and the average concentration in the control area was (11.51 ± 0.28) ppm. The physiological results, included tests&nbsp; such as&nbsp; C-RP, Pb are concerned with the blood of smoking workers in those stations of smokers and indicate the concentration of lead in it to know the extent of the impact of the amount of lead in the gas&nbsp; stations on the health and safety of people.&nbsp; The extent of the impact of smoking as a contributing&nbsp; factor in increasing the percentage of pollution and its impact on human health. The highest concentration of lead in smoking station workers was (31.9&nbsp; ±&nbsp; 0.99) ppm and the lowest concentration was (27.6 ± 1.26) ppm&nbsp;

Increased risk of breast cancer in neurofibromatosis type 1:current insights

Sacha J Howell,1 Kimberley Hockenhull,1 Zena Salih,1 D Gareth Evans2,3 1Department of Medical Oncology, The Christie NHS Foundation Trust, 2Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, 3Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK Abstract: Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by mutation/deletion of the NF1 gene. The gene product, neurofibromin, is a tumor suppressor which represses the activity of the Ras oncogene. Central nervous system (CNS) tumors have long been associated with NF1, but their association with several other malignancies has been demonstrated. In this review, we summarize the epidemiological data that irrefutably support a link between NF1 and an increased risk of early-onset breast cancer, to levels at which annual mammography is currently recommended in national high-risk screening programs. We discuss the reasons for the observed adverse breast cancer prognosis in NF1 cases, including late presentation and more aggressive tumor subtypes, and recommend that a collaborative breast screening study be initiated to better serve this currently underserved population of women. Keywords: breast cancer, neurofibromatosis type 1, NF

Permanent hair loss associated with taxane chemotherapy use in breast cancer: A retrospective survey at two tertiary UK cancer centres.

Purpose: Taxane chemotherapy is commonly used in the management of breast cancer. Hair loss (alopecia) is an expected side effect which may have a significant effect on quality of life. Alopecia is normally temporary but permanent chemotherapy-induced alopecia (pCIA) is increasingly recognised especially following docetaxel chemotherapy. However, the prevalence following docetaxel is not well understood and there is no published literature for paclitaxel chemotherapy. The aim of this study is to investigate the prevalence and patterns of pCIA resulting from both docetaxel and paclitaxel chemotherapy at two tertiary UK cancer centres. Methods: In collaboration between Clatterbridge Cancer Centre and The Christie NHS Foundation Trusts, a retrospective survey was conducted for breast cancer patients who had received taxane chemotherapy in the neoadjuvant and adjuvant settings. Patients who had concluded chemotherapy at least a year previously were contacted by post and invited to participate by completing a questionnaire and returning it to their treatment centre. Data collected included the incidence and pattern of pCIA using the Savin pictorial hair loss scale, and the methods used by patients to manage it. Fisher's exact test was used to compare pCIA between the docetaxel and paclitaxel cohorts. Results: 383 patients responded to the survey (a 63.3% overall response rate). These comprised 245 patients receiving docetaxel and 138 patients treated with paclitaxel. pCIA was reported by 23.3% of patients receiving docetaxel and 10.1% paclitaxel (p &lt; 0.01). Overall 16.7% of patients in both groups reported the ongoing use of products or appliances such as wigs to camouflage their pCIA. In the docetaxel group, pCIA appeared to be more frequent in post-menopausal women than peri- or pre-menopausal women (37.8%, 12.3% and 19.6% respectively [Chi-square test p &lt; 0.01]). Also in the docetaxel group, there appeared to be a trend for more severe scalp alopecia when the patient also received an aromatase inhibitor (AI) or tamoxifen and this difference was most marked in those who had received both an AI and tamoxifen as components of their treatment regime (p = 0.04). The use of scalp cooling was only recorded in the Christie paclitaxel group (n = 12). Of these 12 patients, 83.3% reported no hair loss. While overall rates of permanent eyebrow, eyelash and nostril hair loss were low, this pattern of hair loss appeared more frequent in the paclitaxel than the docetaxel group 4.3% vs. 1.8% (p = 0.29). Conclusions: Both docetaxel and paclitaxel may cause permanent scalp hair loss, but it is significantly more prevalent with docetaxel compared with paclitaxel. Implications for Cancer Survivors: Clinicians should counsel patients regarding the risk of permanent alopecia prior to embarking upon taxane chemotherapy and routinely offer scalp cooling if available. More research is required to understand the pathobiology of this important and previously under recognised long-term side effect to enable more active preventive and management approaches.</p

Home Parenteral Nutrition in Patients with Advanced Cancer: Quality Outcomes from a Centralized Model of Care Delivery

Lack of expertise in home parenteral nutrition (HPN) management has been reported as a barrier to its initiation in patients with advanced cancer (AC), and there are limited data describing hospital readmissions and HPN-related complications. We aimed to assess a centralized approach for managing HPN in AC and evaluate associated outcomes, including hospital readmissions and HPN-related complications. This was a cohort study of adults with AC requiring palliative HPN between 2010&ndash;2018 at a tertiary intestinal failure (IF) center, primarily utilizing a centralized model of HPN oversight to discharge patients remotely from an oncology center to their homes over a wide geographic area. A total of 126 patients were included, with a median distance between the patient&rsquo;s home and the IF center of 17.5 km (IQR 10.9&ndash;39.1; maximum 317.4 km). A total of 28 (22%) patients experienced at least one HPN-related complication, the most common being a central venous catheter (CVC) occlusion and electrolyte abnormalities. The catheter-related bloodstream infection (CRBSI) rate was 0.49/1000 catheter days. The CVC type, administration of concomitant chemotherapy via a distinct CVC lumen separate from PN, venting gastrostomy and distance between the patient&rsquo;s home and the IF center were not associated with CRBSI or mechanical CVC complications. A total of 82 (65.1%) patients were readmitted while on HPN, but only 7 (8.5%) of these readmissions were HPN-related. A total of 44 (34.9%) patients died at home, 41 (32.5%) at a hospice and 41 (32.5%) in a hospital. In conclusion, this study demonstrates that a centralized approach to IF care can provide HPN to patients over a large geographical area while maintaining low HPN-related complications that are comparable to patients requiring HPN for benign conditions and low hospital readmission rates