Department of Oncology, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Breast Cancer Res Treat. 2011 Aug;128(3):755-63. doi: 10.1007/s10549-011-1593-0. Epub 2011 May 29.
Ovarian ablation improves survival in premenopausal early breast cancer, but the potential added value by luteinizing hormone-releasing hormone (LHRH) agonists to tamoxifen is still not clear. The purpose of our study is to examine the efficacy of the LHRH agonist goserelin for adjuvant therapy of premenopausal breast cancer, the role of interaction between goserelin and tamoxifen and the impact of estrogen receptor (ER) content. A total of 927 patients were included in the Stockholm part of the Zoladex in Premenopausal Patients (ZIPP) trial. They were randomly allocated in a 2 × 2 factorial study design to goserelin, tamoxifen, the combination of goserelin and tamoxifen or no endocrine therapy for 2 years, with or without chemotherapy. This is formally not a preplanned subset analysis presenting the end point first event. In this Stockholm sub-study, at a median follow-up of 12.3 years, goserelin reduced the risk of first event by 32% (P = 0.005) in the absence of tamoxifen, and tamoxifen reduced the risk by 27% (P = 0.018) in the absence of goserelin. The combined goserelin and tamoxifen treatment reduced the risk by 24% (P = 0.021) compared with no endocrine treatment. In highly ER-positive tumours, there were 29% fewer events among goserelin treated (P = 0.044) and a trend towards greater risk reduction depending on the level of ER content. The greatest risk reduction from goserelin treatment was observed among those not receiving tamoxifen (HR: 0.52, P = 0.007). In conclusion, goserelin as well as tamoxifen reduces the risk of recurrence in endocrine responsive premenopausal breast cancer. Women with strongly ER-positive tumours may benefit more from goserelin treatment. The combination of goserelin and tamoxifen is not superior to either modality alone. With the limitations of a subset trial, these data have to be interpreted cautiously.
卵巢切除术可改善绝经前早期乳腺癌患者的生存率，但促黄体生成素释放激素（LHRH）激动剂与他莫昔芬联合应用的潜在附加价值尚不清楚。本研究旨在观察 LHRH 激动剂戈舍瑞林用于绝经前乳腺癌辅助治疗的疗效、戈舍瑞林与他莫昔芬的相互作用以及雌激素受体（ER）含量的影响。共有 927 例患者纳入 Zoladex 在绝经前患者（ZIPP）试验的斯德哥尔摩部分。这些患者按 2×2 析因设计随机分为戈舍瑞林、他莫昔芬、戈舍瑞林联合他莫昔芬或无内分泌治疗组，共治疗 2 年，其中部分患者接受化疗，部分患者未接受化疗。这并不是正式的预先计划的亚组分析，本次仅呈现首要终点事件。在这项斯德哥尔摩亚组研究中，中位随访 12.3 年后，在未接受他莫昔芬治疗的患者中，戈舍瑞林使首次事件的风险降低了 32%（P=0.005），在未接受戈舍瑞林治疗的患者中，他莫昔芬使首次事件的风险降低了 27%（P=0.018）。戈舍瑞林联合他莫昔芬治疗使无内分泌治疗的患者的风险降低了 24%（P=0.021）。在高 ER 阳性肿瘤患者中，戈舍瑞林治疗组的事件发生率降低了 29%（P=0.044），且 ER 含量水平越高，降低风险的趋势越明显。未接受他莫昔芬治疗的患者接受戈舍瑞林治疗的获益最大（HR：0.52，P=0.007）。总之，戈舍瑞林和他莫昔芬均可降低内分泌敏感的绝经前乳腺癌的复发风险。ER 阳性肿瘤较强的女性可能从戈舍瑞林治疗中获益更多。戈舍瑞林联合他莫昔芬并不优于单一治疗。由于亚组试验的局限性，这些数据必须谨慎解释。
