Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial.
Twenty-Year Benefit From Adjuvant Goserelin and Tamoxifen in Premenopausal Patients With Breast Cancer in a Controlled Randomized Clinical Trial.
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DOI：
10.1200/jco.21.02844
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发表时间：
2022-12-10
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评估绝经前乳腺癌患者的长期（20年）内分泌治疗获益。对斯德哥尔摩试验（STO-5，1990-1997）的二次分析，将924名绝经前患者随机分配至2年的戈舍瑞林（3.6 mg皮下注射，每28天一次）、他莫昔芬（40 mg口服，每日一次）、戈舍瑞林和他莫昔芬联合治疗组，或不进行辅助内分泌治疗（对照组）。随机分配按淋巴结状态分层;淋巴结阳性患者（n = 459）被分配到标准化疗（环磷酰胺，甲氨蝶呤和氟尿嘧啶）。2020年进行了原发性肿瘤免疫组织化学（n = 731）和基因表达谱（n = 586）。70个基因签名识别了基因组低风险和高风险患者。Kaplan-Meier分析、多变量考克斯比例风险回归和多变量时变灵活参数模型评估了长期无远处复发间期（DRFI）。瑞典高质量的登记系统允许20年的完整随访。在雌激素受体阳性患者中（n = 584，中位年龄47岁），戈舍瑞林，他莫昔芬，以及联合用药与对照组相比，（多变量风险比[HR]，0.49; 95% CI，0.32 - 0.75，HR，0.57; 95% CI，0.38 - 0.87，HR，0.63; 95% CI，0.42 - 0.94）。观察到显著的戈舍瑞林-他莫昔芬相互作用（P = 0.016）。基因组低风险患者（n = 305）显著受益于他莫昔芬（HR，0.24; 95% CI，0.10至0.60），基因组高风险患者（n = 158）显著受益于戈舍瑞林（HR，0.24; 95% CI，0.10至0.54）。在基因组高危患者中观察到他莫昔芬加戈舍瑞林的风险增加（HR，3.36; 95%CI，1.39至8.07）。此外，在基因组低风险患者中观察到他莫昔芬的长期20年获益，而基因组高风险患者则具有早期戈舍瑞林获益。这项研究显示，雌激素受体阳性的绝经前患者接受2年的辅助内分泌治疗可获得20年的获益，并建议根据肿瘤基因组特征进行不同的治疗获益。戈舍瑞林和他莫昔芬联合治疗与单药治疗相比无明显疗效。长期随访以评估治疗获益至关重要。
To assess the long-term (20-year) endocrine therapy benefit in premenopausal patients with breast cancer. Secondary analysis of the Stockholm trial (STO-5, 1990-1997) randomly assigning 924 premenopausal patients to 2 years of goserelin (3.6 mg subcutaneously once every 28 days), tamoxifen (40 mg orally once daily), combined goserelin and tamoxifen, or no adjuvant endocrine therapy (control) is performed. Random assignment was stratified by lymph node status; lymph node–positive patients (n = 459) were allocated to standard chemotherapy (cyclophosphamide, methotrexate, and fluorouracil). Primary tumor immunohistochemistry (n = 731) and gene expression profiling (n = 586) were conducted in 2020. The 70-gene signature identified genomic low-risk and high-risk patients. Kaplan-Meier analysis, multivariable Cox proportional hazard regression, and multivariable time-varying flexible parametric modeling assessed the long-term distant recurrence-free interval (DRFI). Swedish high-quality registries allowed a complete follow-up of 20 years. In estrogen receptor–positive patients (n = 584, median age 47 years), goserelin, tamoxifen, and the combination significantly improved long-term distant recurrence-free interval compared with control (multivariable hazard ratio [HR], 0.49; 95% CI, 0.32 to 0.75, HR, 0.57; 95% CI, 0.38 to 0.87, and HR, 0.63; 95% CI, 0.42 to 0.94, respectively). Significant goserelin-tamoxifen interaction was observed (P = .016). Genomic low-risk patients (n = 305) significantly benefitted from tamoxifen (HR, 0.24; 95% CI, 0.10 to 0.60), and genomic high-risk patients (n = 158) from goserelin (HR, 0.24; 95% CI, 0.10 to 0.54). Increased risk from the addition of tamoxifen to goserelin was seen in genomic high-risk patients (HR, 3.36; 95% CI, 1.39 to 8.07). Moreover, long-lasting 20-year tamoxifen benefit was seen in genomic low-risk patients, whereas genomic high-risk patients had early goserelin benefit. This study shows 20-year benefit from 2 years of adjuvant endocrine therapy in estrogen receptor–positive premenopausal patients and suggests differential treatment benefit on the basis of tumor genomic characteristics. Combined goserelin and tamoxifen therapy showed no benefit over single treatment. Long-term follow-up to assess treatment benefit is critical.