Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer
Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer
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DOI：
10.1093/jnci/91.21.1847
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发表时间：
1999-11-03
期刊：
影响因子：
--
通讯作者：
Sporn, MB
中科院分区：
文献类型：
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作者：
Veronesi, U;De Palo, G;Sporn, MB
背景资料：芬维A胺是一种维生素A类似物，在临床前研究中已显示出抑制乳腺癌的发生。我们确定了芬维A胺在预防乳腺癌妇女的第二种乳腺恶性肿瘤中的疗效。研究方法：我们随机分配了2972名年龄在30-70岁的I期乳腺癌或导管原位癌患者，接受5年的芬维A胺口服（200 mg/天）或不治疗。主要终点是随机分组后7年对侧乳腺癌或同侧乳腺癌的发生率。其他的终点被认为是事后相同的结果分层的绝经状态，远处转移的发生率，总死亡率，和其他器官的肿瘤。用考克斯比例风险回归分析确定乳腺癌发生的危险度。统计检验是双侧的。结果如下：在中位观察时间97个月时，两组之间对侧乳腺癌（P = 0.642）或同侧乳腺癌（P = 0.177）的发生率无统计学显著差异。然而，在两种结局中，均检测到芬维A胺治疗与绝经状态之间的相互作用（两种结局的相互作用P = 0.045），对绝经前妇女可能有有益影响（对侧乳腺癌：校正风险比[HR] = 0.66，95%置信区间[CI] = 0.41-1.07;同侧乳腺癌：校正HR = 0.65，95% CI = 0.46-0.92），绝经后女性中的作用相反（对侧乳腺癌：校正HR = 1.32，95% CI = 0.82-2.15;同侧乳腺癌：校正HR = 1.19，95%CI = 0.75-1.89），两组之间在其他器官肿瘤、远处转移发生率和全因死亡率方面无统计学显著差异。结论：芬维A胺治疗乳腺癌妇女5年似乎对第二乳腺恶性肿瘤的发生率总体上没有统计学显著影响，尽管在绝经前妇女中检测到可能的益处。这些研究，特别是事后分析，被认为是探索性的，需要得到证实。
Background: Fenretinide, a vitamin A analogue, has been shown to inhibit breast carcinogenesis in preclinical studies, We determined the efficacy of fenretinide in preventing a second breast malignancy in women with breast cancer. Methods: We randomly assigned 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ to receive for 5 years either fenretinide orally (200 mg/day) or no treatment. The primary end point was the incidence of contralateral breast cancer or ipsilateral breast cancer 7 years after randomization. Other end points considered post hoc were the same outcomes stratified by menopausal status, incidence of distant metastases, overall mortality, and tumors in other organs. The hazards of breast cancer occurrence mere determined by Cox proportional hazards regression analysis. Statistical tests were two-sided. Results: At a median observation time of 97 months, there were no statistically significant differences in the occurrence of contralateral breast cancer (P = .642) or ipsilateral breast cancer (P = .177) between the two arms. However, an interaction was detected between fenretinide treatment and menopausal status in both outcomes (P for interaction in both outcomes = .045), with a possible beneficial effect in premenopausal women (contralateral breast cancer: adjusted hazard ratio [HR] = 0.66, and 95% confidence interval [CI] = 0.41-1.07; ipsilateral breast cancer: adjusted HR = 0.65, and 95% CI = 0.46-0.92) and an opposite effect in postmenopausal women (contralateral breast cancer: adjusted HR = 1.32, and 95% CI = 0.82-2.15; ipsilateral breast cancer: adjusted HR = 1.19, and 95% CI = 0.75-1.89), There were no statistically significant differences between the two arms in tumors in other organs, incidence of distant metastasis, and all-cause mortality. Conclusions: Fenretinide treatment of women with breast cancer for 5 years appears to have no statistically significant effect on the incidence of second breast malignancies overall, although a possible benefit was detected in premenopausal women. These studies, particularly the post hoc analyses, are considered exploratory and need to be confirmed.