Radiotherapy-related lung fibrosis enhanced by tamoxifen
Radiotherapy-related lung fibrosis enhanced by tamoxifen
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DOI：
10.1093/jnci/88.13.918
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发表时间：
1996-07-03
期刊：
影响因子：
--
通讯作者：
Overgaard, J
中科院分区：
文献类型：
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作者：
Bentzen, SM;Skoczylas, JZ;Overgaard, J
背景资料：他莫昔芬是一种抗雌激素药物，在乳腺癌治疗中具有良好的疗效和低毒性。然而，他莫昔芬已被证明具有许多非激素和激素效应，他莫昔芬的一种非激素效应是诱导转化生长因子β由于TGF-β的分泌，TGF-β参与了辐射诱导的纤维化的发病机制，目的：我们研究了乳腺癌患者在乳房切除术后接受放疗，同时接受或不接受他莫昔芬辅助治疗后肺纤维化的发展。来自196名妇女的数据被纳入分析，84名绝经后妇女参加了一项随机试验，试验中测试了他莫昔芬作为乳房切除术后放疗的辅助药物，放射治疗技术采用8 MV光子野，覆盖胸部患侧的腋窝和锁骨下和锁骨上区域;用电子束照射胸壁，观察治疗前后胸部X线片光密度的变化，以监测肺纤维化的发展;仅在光子照射野评估肺反应，使用Logistic回归分析来探讨接受或未接受他莫昔芬的患者中放射剂量与肺纤维化发展的关系，所有P值均来自双侧检验。在84名参与放疗加他莫昔芬（n = 38）与单纯放疗（n = 46）的随机试验的妇女中，他莫昔芬治疗与显著肺纤维化的发生率之间存在显著相关性（相对危险度= 2.0; 95%置信区间[CI] = 1.2-3.5; P = 0.01），当使用逻辑回归分析评估所有196例患者的数据时，发现肺纤维化的发生率与总辐射剂量之间存在高度显著的关系。（P = .0005），在全面分析中，再次发现接受他莫昔芬与放疗同时治疗的患者发生显著肺纤维化的风险增加。（仅接受放疗的患者作为参照，比值比= 2.9; 95% CI = 1.3-6.3; P = 0.007），患者年龄和绝经状态对结果无显著影响，结论：乳腺切除术后放疗期间他莫昔芬治疗增加了放射性肺纤维化的风险，鉴于已有的数据，我们假设他莫昔芬通过诱导TGF-β分泌介导辐射诱导的肺纤维化的增强。如果这一假设是正确的，可能会设计新的策略来预防或减少辐射诱导的纤维化，由于我们研究的是相对较小的照射肺，我们不能建议改变目前的治疗措施，但是，我们强烈鼓励对接受他莫昔芬和放疗的患者进行肺纤维化的额外研究。
Background: Tamoxifen is an antiestrogen with proven efficacy and low toxicity in the treatment of breast cancer, However, tamoxifen has been shown to exert a number of nonhormonal as well as hormonal effects, One nonhormonal effect of tamoxifen is the induction of transforming growth factor-beta (TGF-beta) secretion, TGF-beta has been implicated in the pathogenesis of radiation-induced fibrosis, Purpose: We investigated the development of lung fibrosis in breast cancer patients who were treated after mastectomy with radiotherapy, with or without simultaneous adjuvant treatment with tamoxifen, Methods: Data from 196 women were included in the analysis, Eighty-four women were postmenopausal patients who participated in a randomized trial testing tamoxifen as an adjuvant to postmastectomy radiotherapy, The radiotherapy technique employed an 8-MV photon field covering the axillary and the infraclavicular and supraclavicular regions of the affected side of the chest; the chest wall was treated with an abutted electron field, Optical density changes in pretreatment and post-treatment chest x-ray films were used to monitor the development of lung fibrosis; lung reactions were assessed in the photon-irradiated field only, Logistic regression analysis was used to explore relationships between radiation dose and the development of lung fibrosis in patients either receiving or not receiving tamoxifen, All P values are from two-sided tests, Results: Among the 84 women who participated in the randomized trial of radiotherapy plus tamoxifen (n = 38) versus radiotherapy alone (n = 46), there was a significant association between tamoxifen treatment and the incidence of marked lung fibrosis (relative risk = 2.0; 95% confidence interval [CI] = 1.2-3.5; P = .01), When logistic regression analysis was used to evaluate data from all 196 patients, a highly significant relationship was found between the incidence of lung fibrosis and total radiation dose (P = .0005), In the full analysis, an increased risk of marked lung fibrosis was found again for patients who received tamoxifen simultaneously with radiotherapy (with patients receiving radiotherapy alone as the referent, odds ratio = 2.9; 95% CI = 1.3-6.3; P = .007), Patient age and menopausal status did not significantly influence the results, Conclusion: Tamoxifen treatment during postmastectomy radiotherapy enhances the risk of radiation-induced lung fibrosis, Implications: In view of pre-existing data, we hypothesize that tamoxifen mediates the enhancement of radiation-induced lung fibrosis through the induction of TGF-beta secretion, If this hypothesis is correct, new strategies might be devised for preventing or reducing radiation-induced fibrosis, Because we studied a relatively small portion of the irradiated lung, we cannot recommend changes in current therapeutic measures; however, we strongly encourage additional studies of lung fibrosis in patients receiving tamoxifen and radiotherapy.