背景:激素受体阳性可预测内分泌治疗的益处,但关于不同肿瘤受体水平患者长期生存的知识有限。在这项研究中,我们描述了他莫昔芬(TAM)治疗患者的25年结局.
方法:在1983年至1992年之间,共有4,610名绝经后早期乳腺癌患者被随机分配接受2或5年的TAM治疗。两年后,4,124例存活且无乳腺癌复发。其中,2,481例已经证明了雌激素受体阳性(ER+)疾病。从1988年开始,Abbot酶免疫测定开始可用,并为1,210名患者提供了定量受体水平,为此我们进行了分析。
结果:经过5年的随访,当所有的TAM治疗完成后,直到15年的随访,与2年组相比,5年组ER+疾病患者的乳腺癌死亡率显著降低(风险比[HR]0.67,95%置信区间[CI]0.55~0.83,p<0.001).15年后,两组间的差异仍然存在,但没有进一步增加.仅在ER水平低于中位数的患者亚组中观察到延长TAM治疗的实质性益处(HR=0.62,95%CI0.46-0.84,p=0.002)。同样,孕激素受体阴性(PR-)病患者确实从延长TAM治疗中获益.对于孕激素受体阳性(PR+)疾病的患者,TAM治疗2年以上无统计学意义的获益.解释:与2年的佐剂TAM相比,5年显著延长乳腺癌特异性生存期。对于ER水平低于中位数或PR阴性疾病的患者,延长TAM治疗的益处具有统计学意义。对于具有高ER水平或具有PR+肿瘤的患者,延长TAM没有明显的益处。
BACKGROUND: Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this
study, we describe the 25 years outcome of
tamoxifen (TAM) treated patients.
METHODS: Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done.
RESULTS: After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM. Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.