Castiglione-Gertsch Monica, O'Neill Anne, Price Karen N, Goldhirsch Aron, Coates Alan S, Colleoni Marco, Nasi M Laura, Bonetti Marco, Gelber Richard D
International Breast Cancer Study Group Coordinating Center and Inselspital, Bern, Switzerland.
J Natl Cancer Inst. 2003 Dec 17;95(24):1833-46. doi: 10.1093/jnci/djg119.
Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the efficacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node-negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone.
From March 1990 through October 1999, 1063 patients stratified by estrogen receptor (ER) status and radiotherapy plan were randomly assigned to receive goserelin for 24 months (n = 346), six courses of "classical" CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or six courses of classical CMF followed by 18 months of goserelin (CMF --> goserelin; n = 357). A fourth arm (no adjuvant treatment) with 46 patients was discontinued in 1992. Tumors were classified as ER-negative (30%), ER-positive (68%), or ER status unknown (3%). Twenty percent of patients were aged 39 years or younger. The median follow-up was 7 years. The primary outcome was disease-free survival (DFS).
Patients with ER-negative tumors achieved better disease-free survival if they received CMF (5-year DFS for CMF = 84%, 95% confidence interval [CI] = 77% to 91%; 5-year DFS for CMF --> goserelin = 88%, 95% CI = 82% to 94%) than if they received goserelin alone (5-year DFS = 73%, 95% CI = 64% to 81%). By contrast, for patients with ER-positive disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year DFS for both treatment groups = 81%, 95% CI = 76% to 87%), whereas sequential therapy (5-year DFS = 86%, 95% CI = 82% to 91%) provided a statistically nonsignificant improvement compared with either modality alone, primarily because of the results among younger women.
Premenopausal women with ER-negative (i.e., endocrine nonresponsive), lymph node-negative breast cancer should receive adjuvant chemotherapy. For patients with ER-positive (i.e., endocrine responsive) disease, the combination of chemotherapy with ovarian function suppression or other endocrine agents, and the use of endocrine therapy alone should be studied.
虽然化疗和卵巢功能抑制对早期乳腺癌患者都是有效的辅助治疗方法，但对于它们序贯联合使用的疗效却知之甚少。在一项针对绝经前和围绝经期淋巴结阴性乳腺癌女性的国际乳腺癌研究组（IBCSG）随机临床试验（试验VIII）中，我们比较了序贯化疗后使用促性腺激素释放激素激动剂戈舍瑞林与单独使用每种治疗方法的疗效。
从1990年3月至1999年10月，1063例根据雌激素受体（ER）状态和放疗计划分层的患者被随机分配接受戈舍瑞林治疗24个月（n = 346）、六个疗程的“经典”CMF（环磷酰胺、甲氨蝶呤、5-氟尿嘧啶）化疗（n = 360）或六个疗程的经典CMF化疗后再接受18个月的戈舍瑞林治疗（CMF→戈舍瑞林；n = 357）。第四组（无辅助治疗）的46例患者于1992年退出研究。肿瘤被分类为ER阴性（30%）、ER阳性（68%）或ER状态未知（3%）。20%的患者年龄在39岁及以下。中位随访时间为7年。主要结局是无病生存期（DFS）。
ER阴性肿瘤患者接受CMF治疗（CMF的5年DFS = 84%，95%置信区间[CI] = 77%至91%；CMF→戈舍瑞林的5年DFS = 88%，95%CI = 82%至94%）时的无病生存期优于单独接受戈舍瑞林治疗（5年DFS = 73%，95%CI = 64%至81%）。相比之下，对于ER阳性疾病患者，单独化疗和单独使用戈舍瑞林的疗效相似（两个治疗组的5年DFS均 = 81%，95%CI = 76%至87%），而序贯治疗（5年DFS = 86%，95%CI = 82%至91%）与单独使用任何一种治疗方法相比，改善情况在统计学上无显著意义，主要是由于年轻女性的结果。
绝经前ER阴性（即内分泌无反应）、淋巴结阴性乳腺癌女性应接受辅助化疗。对于ER阳性（即内分泌有反应）疾病患者，应研究化疗与卵巢功能抑制或其他内分泌药物联合使用以及单独使用内分泌治疗的情况。
