Diamandidou E, Buzdar A U, Smith T L, Frye D, Witjaksono M, Hortobagyi G N
Department of Breast and Gynecologic Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
J Clin Oncol. 1996 Oct;14(10):2722-30. doi: 10.1200/JCO.1996.14.10.2722.
Adjuvant chemotherapy for breast cancer has been the routine practice in the past decade. A number of studies have observed an increased incidence of treatment-related leukemias following chemotherapy with alkylating agents and/or topoisomerase II inhibitors. We evaluated the incidence of treatment-related leukemias in breast cancer patients treated in four adjuvant and two neoadjuvant chemotherapy trials at The University of Texas M.D. Anderson Cancer Center.
Between 1974 and 1989, 1,474 patients with stage II or III breast cancer were treated in six prospective trials of adjuvant (n = 4) or neoadjuvant (n = 2) chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (CTX) (FAC) with or without other drugs. The median observation time was 97 months. In 1,107 patients, FAC chemotherapy was given postoperatively; 367 patients received induction chemotherapy, as well as postoperative chemotherapy. Eight hundred ten patients had surgery followed by radiotherapy and chemotherapy; 664 patients had surgery and chemotherapy only. Patients in two adjuvant and one neoadjuvant study received higher cumulative doses of CTX compared with those in the other studies.
Fourteen cases of leukemia were observed. Twelve of these patients had received radiotherapy and chemotherapy, and two had received chemotherapy only. Six of the reported patients with leukemia were treated with a cumulative CTX dose of greater than 6 g/ m2. Five of these patients had received both radiotherapy and chemotherapy. The median latency period in the 14 patients was 66 months (range, 22 to 113). Six of 10 patients with adequate cytogenetic analyses had abnormalities that involved chromosomes 5 and/or 7. The rest of the patients had nonspecific cytogenetic abnormalities or lacked cytogenetic information. The 10-year estimated leukemia rate was 1.5% (95% confidence interval [CI], 0.7% to 2.9%) for all patients treated, 2.5% (95% CI, 1.0% to 5.1%) for the radiotherapy-plus-chemotherapy group, and 0.5% (95% CI, 0.1% to 2.4%) for the chemotherapy-only group; this difference was statistically significant (P = .01). The 10-year estimated leukemia risk for the higher-dose (> 6 g/m2) CTX group was 2% (95% CI, 0.5% to 5.0%) compared with 1.3% (95% CI, 0.4% to 3.0%) for the lower-dose group, a difference that was not statistically significant (P = .53).
These data illustrate that patients treated with adjuvant FAC chemotherapy plus radiotherapy have a slightly increased risk of leukemia. This information needs to be considered in the treatment plans for patients with breast cancer. However, for most patients, the benefits of adjuvant therapy exceed the risk of treatment-related leukemia.
在过去十年中，辅助化疗一直是乳腺癌的常规治疗方法。多项研究观察到，使用烷化剂和/或拓扑异构酶II抑制剂进行化疗后，与治疗相关的白血病发病率有所增加。我们评估了得克萨斯大学MD安德森癌症中心四项辅助化疗试验和两项新辅助化疗试验中乳腺癌患者与治疗相关的白血病发病率。
1974年至1989年间，1474例II期或III期乳腺癌患者参加了六项前瞻性辅助化疗（n = 4）或新辅助化疗（n = 2）试验，使用氟尿嘧啶、多柔比星和环磷酰胺（CTX）（FAC），可联合或不联合其他药物。中位观察时间为97个月。1107例患者术后接受FAC化疗；367例患者接受诱导化疗及术后化疗。810例患者手术后接受放疗和化疗；664例患者仅接受手术和化疗。与其他研究中的患者相比，两项辅助研究和一项新辅助研究中的患者接受了更高累积剂量的CTX。
观察到14例白血病病例。其中12例患者接受了放疗和化疗，2例仅接受了化疗。报告的白血病患者中有6例接受的CTX累积剂量大于6 g/m2。其中5例患者接受了放疗和化疗。14例患者的中位潜伏期为66个月（范围22至113个月）。10例进行了充分细胞遗传学分析的患者中有6例存在涉及5号和/或7号染色体的异常。其余患者有非特异性细胞遗传学异常或缺乏细胞遗传学信息。所有接受治疗的患者10年白血病估计发生率为1.5%（95%置信区间[CI]，0.7%至2.9%），放疗加化疗组为2.5%（95%CI，1.0%至5.1%），单纯化疗组为0.5%（95%CI，0.1%至2.4%）；差异有统计学意义（P = 0.01）。高剂量（>6 g/m2）CTX组的10年白血病估计风险为2%（95%CI，0.5%至5.0%），低剂量组为1.3%（95%CI，0.4%至3.0%），差异无统计学意义（P = ０.53）。
这些数据表明，接受辅助FAC化疗加放疗的患者患白血病的风险略有增加。在乳腺癌患者的治疗计划中需要考虑这一信息。然而，对于大多数患者来说，辅助治疗的益处超过了与治疗相关的白血病风险。
