Kaufmann M, Jonat W, Abel U, Hilfrich J, Caffier H, Kreienberg R, Trams G, Brunnert K, Schermann J, Kleine W
Gynecological Adjuvant Breast Group, Germany.
J Clin Oncol. 1993 Mar;11(3):454-60. doi: 10.1200/JCO.1993.11.3.454.
We report two randomized trials of adjuvant systemic therapy in 747 patients < or = 65 years of age with histologically proven node-positive breast cancer.
Patients were selected for the two trials on the basis of lymph node and hormone receptor status. The only stratification was based on the treating institution. In patients with a lower probability of recurrence (n = 276), a comparison between endocrine therapy (tamoxifen [Tam] 30 mg/d for 2 years) and chemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF] intravenously [IV], six cycles every 4 weeks) was performed. In patients with a higher risk of recurrence (n = 471), a comparison between chemotherapy alone (doxorubicin plus cyclophosphamide [AC] i.v., eight cycles every 3 weeks) and the same chemotherapy plus Tam was made.
Overall, we found that CMF and Tam are equally effective in a subgroup of patients with a relatively good prognosis (low-risk patients). However, in the subset of women < or = 49 years old, a significantly greater disease-free survival (DFS) rate (P = .01) and overall survival (OS) rate (P = .002) was observed following therapy with CMF compared with Tam. In patients > or = 50 years old, the opposite was found, and Tam appeared to be superior to CMF (DFS, P = .003; OSm P = .5). These results must be interpreted cautiously, since a post-hoc stratification of patients by age (< or = 49, > or = 50) was performed, and significantly more younger, low-risk patients were randomized to receive chemotherapy alone and more older patients to receive Tam alone. Among patients with a relatively poor prognosis (high-risk patients), a combination of AC plus Tam was equivalent to AC and, when women were analyzed by age, this was found to be true of patients < or = 49 years as well. However, the addition of Tam to AC in women age > or 50 years resulted in a statistically significantly higher DFS (P = .01) and a trend toward better OS compared with women who received AC alone.
Further trials are required to analyze the role of combined simultaneous or sequential chemoendocrine adjuvant treatment or each single therapy alone in defined risk-adapted subsets of node-negative and node-positive patients.
我们报告了两项针对747例年龄≤65岁、组织学证实为淋巴结阳性乳腺癌患者的辅助全身治疗随机试验。
根据淋巴结和激素受体状态选择患者进行这两项试验。唯一的分层依据是治疗机构。在复发可能性较低的患者（n = 276）中，比较了内分泌治疗（他莫昔芬[Tam]30 mg/d，持续2年）与化疗（环磷酰胺、甲氨蝶呤和氟尿嘧啶[CMF]静脉注射[IV]，每4周6个周期）。在复发风险较高的患者（n = 471）中，比较了单纯化疗（阿霉素加环磷酰胺[AC]静脉注射，每3周8个周期）与相同化疗加Tam的效果。
总体而言，我们发现CMF和Tam在预后相对较好的亚组患者（低风险患者）中同样有效。然而，在年龄≤49岁的女性亚组中，与Tam相比，CMF治疗后的无病生存率（DFS）（P = 0.01）和总生存率（OS）（P = 0.002）显著更高。在年龄≥50岁的患者中，结果相反，Tam似乎优于CMF（DFS，P = 0.003；OS，P = 0.5）。这些结果必须谨慎解读，因为是对患者按年龄（≤49岁、≥50岁）进行事后分层，且明显更多年轻、低风险患者被随机分配接受单纯化疗，更多老年患者接受单纯Tam治疗。在预后相对较差的患者（高风险患者）中，AC加Tam的联合治疗与AC等效，按年龄分析女性患者时，年龄≤49岁的患者也是如此。然而，在年龄＞50岁的女性中，AC加Tam治疗后的DFS在统计学上显著更高（P = 0.01），与单纯接受AC治疗的女性相比，OS有改善趋势。
需要进一步试验来分析联合同步或序贯化疗内分泌辅助治疗或每种单一治疗在明确的淋巴结阴性和阳性患者风险适应性亚组中的作用。
