ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

2005 ◽  
Author(s):  
Barry S. Rosenstein
Keyword(s):  
Breast Cancer ◽  
Radiation Induced

scholarly journals Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1992
Author(s):  
Max Seidensticker ◽  
Matthias Philipp Fabritius ◽  
Jannik Beller ◽  
Ricarda Seidensticker ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Disease ◽  
Positive Impact ◽  
Metastatic Breast ◽  
Normal Liver ◽  
Liver Parenchyma ◽  
Breast Cancer Patients ◽  
Radiation Induced ◽  
The Impact

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

scholarly journals A radiosensitizer, gallotannin-rich extract from Bouea macrophylla seeds, inhibits radiation-induced epithelial-mesenchymal transition in breast cancer cells

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiraporn Kantapan ◽  
Siwaphon Paksee ◽  
Aphidet Duangya ◽  
Padchanee Sangthong ◽  
Sittiruk Roytrakul ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Cell Death ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Cell Lines ◽  
Mesenchymal Transition ◽  
Mammosphere Formation ◽  
Radiation Induced

Abstract Background Radioresistance can pose a significant obstacle to the effective treatment of breast cancers. Epithelial–mesenchymal transition (EMT) is a critical step in the acquisition of stem cell traits and radioresistance. Here, we investigated whether Maprang seed extract (MPSE), a gallotannin-rich extract of seed from Bouea macrophylla Griffith, could inhibit the radiation-induced EMT process and enhance the radiosensitivity of breast cancer cells. Methods Breast cancer cells were pre-treated with MPSE before irradiation (IR), the radiosensitizing activity of MPSE was assessed using the colony formation assay. Radiation-induced EMT and stemness phenotype were identified using breast cancer stem cells (CSCs) marker (CD24−/low/CD44+) and mammosphere formation assay. Cell motility was determined via the wound healing assay and transwell migration. Radiation-induced cell death was assessed via the apoptosis assay and SA-β-galactosidase staining for cellular senescence. CSCs- and EMT-related genes were confirmed by real-time PCR (qPCR) and Western blotting. Results Pre-treated with MPSE before irradiation could reduce the clonogenic activity and enhance radiosensitivity of breast cancer cell lines with sensitization enhancement ratios (SERs) of 2.33 and 1.35 for MCF7 and MDA-MB231cells, respectively. Pretreatment of breast cancer cells followed by IR resulted in an increased level of DNA damage maker (γ-H2A histone family member) and enhanced radiation-induced cell death. Irradiation induced EMT process, which displayed a significant EMT phenotype with a down-regulated epithelial marker E-cadherin and up-regulated mesenchymal marker vimentin in comparison with untreated breast cancer cells. Notably, we observed that pretreatment with MPSE attenuated the radiation-induced EMT process and decrease some stemness-like properties characterized by mammosphere formation and the CSC marker. Furthermore, pretreatment with MPSE attenuated the radiation-induced activation of the pro-survival pathway by decrease the expression of phosphorylation of ERK and AKT and sensitized breast cancer cells to radiation. Conclusion MPSE enhanced the radiosensitivity of breast cancer cells by enhancing IR-induced DNA damage and cell death, and attenuating the IR-induced EMT process and stemness phenotype via targeting survival pathways PI3K/AKT and MAPK in irradiated breast cancer cells. Our findings describe a novel strategy for increasing the efficacy of radiotherapy for breast cancer patients using a safer and low-cost natural product, MPSE.

Designing Personalized Treatment Plans for Breast Cancer

2021 ◽  
Author(s):  
Wei Chen ◽  
Yixin Lu ◽  
Liangfei Qiu ◽  
Subodha Kumar
Keyword(s):  
Breast Cancer ◽  
Domain Knowledge ◽  
Early Stage ◽  
Radiotherapy Planning ◽  
Breast Cancer Patients ◽  
Support Tools ◽  
Treatment Plans ◽  
Radiation Induced ◽  
Effective Decision ◽  
Effective Decision Support

Breast cancer remains the leading cause of cancer deaths among women around the world. Contemporary treatment for breast cancer is complex and involves highly specialized medical professionals collaborating in a series of information-intensive processes. This poses significant challenges to optimization of treatment plans for individual patients. We propose a novel framework that enables personalization and customization of treatment plans for early stage breast cancer patients undergoing radiotherapy. Using a series of simulation experiments benchmarked with real-world clinical data, we demonstrate that the treatment plans generated from our proposed framework consistently outperform those from the existing practices in balancing the risk of local tumor recurrence and radiation-induced adverse effects. Our research sheds new light on how to combine domain knowledge and patient data in developing effective decision-support tools for clinical use. Although our research is specifically geared toward radiotherapy planning for breast cancer, the design principles of our framework can be applied to the personalization of treatment plans for patients with other chronic diseases that typically involve complications and comorbidities.

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