Veronesi U, Mariani L, Decensi A, Formelli F, Camerini T, Miceli R, Di Mauro M G, Costa A, Marubini E, Sporn M B, De Palo G
European Institute of Oncology, Milan, Italy.
Ann Oncol. 2006 Jul;17(7):1065-71. doi: 10.1093/annonc/mdl047. Epub 2006 May 4.
The synthetic retinoid fenretinide administered for 5 years for prevention of second breast cancer showed no difference after a median of 8 years, but a possible reduction in premenopausal women. We conducted a long-term analysis in a subgroup of women who were regularly followed up in a single center.
We analyzed data after a median follow-up of 14.6 years (IQ range, 12.3-16.3 years) from 1739 women aged 30-70 (872 in the fenretinide arm and 867 in the observation arm), representing 60% of the initial cohort of 2867 women. The main efficacy endpoint was second primary breast cancer (contralateral or ipsilateral).
The number of second breast cancers was 168 in the fenretinide arm and 190 in the control arm (hazard ratio = 0.83, 95% CI, 0.67-1.03). There were 83 events in the fenretinide arm and 126 in the observation arm in premenopausal women (HR = 0.62, 95% CI, 0.46-0.83), and 85 and 64 events in postmenopausal women (HR = 1.23, 95% CI, 0.63-2.40). The younger were the women, the greater was the risk reduction associated with fenretinide, which attained 50% in women aged 40 years or younger and disappeared after age 55 (P-age*treatment interaction = 0.023). There was no difference in cancers in other organs, distant metastases or survival.
Fenretinide induces a significant risk reduction of second breast cancer in premenopausal women, which is remarkable at younger ages, and persists several years after treatment cessation. Since adverse events are limited, a trial in young women at high-risk is warranted.
合成维甲酸类药物芬维A胺用于预防对侧乳腺癌，给药5年，在中位随访8年后未显示出差异，但对绝经前女性可能有降低作用。我们在一个单一中心定期随访的女性亚组中进行了一项长期分析。
我们分析了1739名年龄在30 - 70岁女性（芬维A胺组872名，观察组867名）的数据，这些数据来自中位随访14.6年（四分位间距，12.3 - 16.3年）的结果，占初始队列2867名女性的60%。主要疗效终点是对侧或同侧的第二原发性乳腺癌。
芬维A胺组第二原发性乳腺癌的病例数为168例，对照组为190例（风险比 = 0.83，95%置信区间，0.67 - 1.03）。绝经前女性中，芬维A胺组有83例事件，观察组有126例事件（风险比 = 0.62，95%置信区间，0.46 - 0.83）；绝经后女性中分别有85例和64例事件（风险比 = 1.23，95%置信区间，0.63 - 2.40）。女性年龄越小，与芬维A胺相关的风险降低幅度越大，40岁及以下女性中降低幅度达到50%，55岁后消失（年龄*治疗交互作用P值 = 0.023）。其他器官的癌症、远处转移或生存率方面没有差异。
芬维A胺可显著降低绝经前女性患第二原发性乳腺癌的风险，在年轻女性中尤为显著，且在停药后数年仍持续存在。由于不良事件有限，有必要对高危年轻女性进行试验。
