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Children with cancer previously treated with radiotherapy face the likelihood of side effects that can be debilitating or fatal. This study aimed to assess the long-term effect of medulloblastoma radiotherapy on the DNA double-strand break (DSB) repair capability of primary fibroblasts derived from lung biopsies of previously irradiated young sheep. This study included biopsies from three control and five irradiated sheep. The treated sheep had previously received spinal radiotherapy at a total dose of 28 Gy, which is equivalent to pediatric medulloblastoma treatment. Lung biopsies were taken 4 years post-irradiation from high-dose (HD, >18 Gy) and low-dose (LD, <2 Gy) regions. Fifteen cell lines were extracted (six control, four LD and five HD). The cells were irradiated, and DNA DSB repair was analyzed by immunofluorescence. Clonogenic, trypan blue and micronuclei assays were performed. Both the HD and LD cell lines had a significantly higher number of residual γH2AX foci 24 h and a significant decrease in pATM activity post-irradiation compared to the control. There was no statistically significant difference in the clonogenic assay, trypan blue and micronuclei results. Our study showed that a previous irradiation can impair the DNA DSB repair mechanism of ovine lung fibroblasts.

Breast reconstruction (BR) after mastectomy is important to consider for a woman's body image enhancement and psychological well-being. Although post-mastectomy radiation (PMRT) significantly improves the outcome of patients with high-risk breast cancer (BC), PMRT after BR may affect cosmetic outcomes and may compromise the original goal of improving quality of life (QoL). With the lack of practical guidelines, it seems essential to work on a consensus and provide some "expert agreements" to offer patients the best option for PMRT after BR. We report a global "expert agreement" that results from a critical review of the literature on BR and PMRT during the 6th international multidisciplinary breast conference in March 2023., Competing Interests: Declaration of Competing Interest None, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Early-stage breast cancer is usually treated with breast-conserving surgery followed by adjuvant radiation therapy. Acute skin toxicity is a common radiation-induced side effect experienced by many patients. Recently, a combination of bisphosphonates (zoledronic acid) and statins (pravastatin), or ZOPRA, was shown to radio-protect normal tissues by enhancing DNA double-strand breaks (DSB) repair mechanism. However, there are no studies assessing the effect of ZOPRA on cancerous cells. The purpose of this study is to characterize the in vitro effect of the zoledronic acid (ZO), pravastatin (PRA), and ZOPRA treatment on the molecular and cellular radiosensitivity of breast cancer cell lines., Materials: Two breast cancer cell lines, MDA MB 231 and MCF-7, were tested. Cells were treated with different concentrations of pravastatin (PRA), zoledronate (ZO), as well as their ZOPRA combination, before irradiation. Anti-γH2AX and anti-pATM immunofluorescence were performed to study DNA DSB repair kinetics. MTT assay was performed to assess cell proliferation and viability, and flow cytometry was performed to analyze the effect of the drugs on the cell cycle distribution. The clonogenic assay was used to assess cell survival., Results: ZO, PRA, and ZOPRA treatments were shown to increase the residual number of γH2AX foci for both cell lines. ZOPRA treatment was also shown to reduce the activity of the ATM kinase in MCF-7. ZOPRA induced a significant decrease in cell survival for both cell lines., Conclusions: Our findings show that pretreatment with ZOPRA can decrease the radioresistance of breast cancer cells at the molecular and cellular levels. The fact that ZOPRA was previously shown to radioprotect normal tissues, makes it a good candidate to become a therapeutic window-widening drug., (© 2023. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Introduction: Breast cancer is the most frequent cancer among Emirati women and is the second leading cause of death among women in the UAE. To date, published studies regarding breast cancer in the UAE have investigated a mixed population of different ethnicities with a low percentage of UAE nationals. This is the first study to highlight the clinical and pathological data of a large cohort of exclusively Emirati national breast cancer patients diagnosed at a tertiary care medical facility., Materials and Methods: This is a retrospective study involving breast cancer patients in UAE women who were evaluated and/or treated at the Cleveland Clinic Abu Dhabi during the period from May 2015 until June 2021., Results: This study initially included 372 participants. The median age at diagnosis was 48 years (24-86 years) and 12.3% of patients had screening detected tumors. 30% of patients presented with locally advanced disease and 20% had stage IV disease at presentation. 24% were 40 years or younger at the time of diagnosis., Discussion: To our knowledge, this is the largest study to date focusing exclusively on the presentation and characteristics of Emirati women with breast cancer. The median age of incidence was 48 years and the percentage of patients diagnosed with breast cancer at age 40 or younger years was 24%. This is an agreement with data published in the Middle East, but is significantly below what is reported in Caucasian women in the Western world. In this study, Emirati patients presented with advanced stages of disease. More advanced disease, and higher stage 4 at presentation is another reflection of the low screening rates, but also an indication of a higher patient thresholds for reporting breast health concerns to medical professionals for evaluation., Conclusion: Findings of our study do suggest the need to focus efforts on continuing to understand the exact presentation of breast cancer among Emirati women and underscore the need to pursue efforts to improve public education, increase screening utilization and early detection to reduce the burden of disease and address an essential health care need for this unique population.