AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to ...AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients' personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale. RESULTS: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed. CONCLUSION: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.展开更多
Hormone Receptor positive (HR+) breast cancer is the most common malignancy in women. New strategies in the treatments have targeted the estrogen biosynthesis pathways including the inhibition of the aromatase and 17...Hormone Receptor positive (HR+) breast cancer is the most common malignancy in women. New strategies in the treatments have targeted the estrogen biosynthesis pathways including the inhibition of the aromatase and 17β-HSD1 enzymes. The present work, describes the study of a new family of 9 hybrid compounds derived from estrone attached to a coumarin fragment, linked through different lengths of hydrocarbon chains. The activity of these compounds was evaluated by molecular docking with two relevant enzymes in breast cancer (HR+). It has been proposed nine compounds as 17β-HSD1 inhibitors and six as aromatase inhibitors. We found important interactions with key amino acids at the orthosteric site of each enzyme and their score values compared to the crystallographic ligand. The in silico analysis showed good score values in the proposed compounds, where the steroidal portion presented important interactions with Met374 and Tyr155 in aromatase and in 17β-HSD1 respectively. Highlighting Compounds 2, 5 and 8 with an aromatic ring at the C4 position of the coumarin moiety, which favored arene-H type interactions essential for protein-ligand recognition. In addition, the results related to the 17β-HSD1 enzyme demonstrated how the length of the linker influences the interaction;the best score was found for derivative 8 with a chain of 8 methylenes.展开更多
探讨骨密度评分(bone mineral density-Tscore,BMD-T)结合6号染色体(estrogen receptor 1,ESR1)基因多态性的组合评估方法用于非骨质疏松的绝经后乳腺癌人群长期使用来曲唑骨流失风险评估的可行性。选取2020年7月—2021年5月就诊于江南...探讨骨密度评分(bone mineral density-Tscore,BMD-T)结合6号染色体(estrogen receptor 1,ESR1)基因多态性的组合评估方法用于非骨质疏松的绝经后乳腺癌人群长期使用来曲唑骨流失风险评估的可行性。选取2020年7月—2021年5月就诊于江南大学附属无锡妇产医院的240例绝经后女性乳腺癌患者为研究对象,所有患者仅使用曲唑片2.5 mg/天进行内分泌治疗。将患者随机分入BMD-T评分组(A)、ESR1基因多态性评估组(B)、组合评估高风险组、组合评估低风险组,每组各60例,高低风险人数比例为1:1。半年、一年后检查骨密度,两两比较各组骨流失发生率的差异。结果表明,组合评估高风险组在一年后能覆盖最多的骨流失人群(30%)。研究发现,BMD-T评分在﹣1.0以上的人群不需要进行ESR1基因多态性评估;BMD-T评分为﹣2.5~﹣1.0的人群使用组合评估高风险策略具有可行性。展开更多
文摘AIM: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients. METHODS: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients' personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale. RESULTS: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed. CONCLUSION: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.
文摘Hormone Receptor positive (HR+) breast cancer is the most common malignancy in women. New strategies in the treatments have targeted the estrogen biosynthesis pathways including the inhibition of the aromatase and 17β-HSD1 enzymes. The present work, describes the study of a new family of 9 hybrid compounds derived from estrone attached to a coumarin fragment, linked through different lengths of hydrocarbon chains. The activity of these compounds was evaluated by molecular docking with two relevant enzymes in breast cancer (HR+). It has been proposed nine compounds as 17β-HSD1 inhibitors and six as aromatase inhibitors. We found important interactions with key amino acids at the orthosteric site of each enzyme and their score values compared to the crystallographic ligand. The in silico analysis showed good score values in the proposed compounds, where the steroidal portion presented important interactions with Met374 and Tyr155 in aromatase and in 17β-HSD1 respectively. Highlighting Compounds 2, 5 and 8 with an aromatic ring at the C4 position of the coumarin moiety, which favored arene-H type interactions essential for protein-ligand recognition. In addition, the results related to the 17β-HSD1 enzyme demonstrated how the length of the linker influences the interaction;the best score was found for derivative 8 with a chain of 8 methylenes.
