Sigurdsson H, Baldetorp B, Borg A, Dalberg M, Fernö M, Killander D, Olsson H
Department of Oncology, University Hospital, Lund, Sweden.
N Engl J Med. 1990 Apr 12;322(15):1045-53. doi: 10.1056/NEJM199004123221505.
Measures of the proliferative activity of tumor cells have prognostic value in patients with node-negative breast cancer. We studied 367 women in southern Sweden who had undergone surgical resection for such cancer. Tumor specimens were analyzed with DNA flow cytometry in order to estimate both the DNA content (ploidy) and the fraction of cells in the synthetic phase of the cell cycle (S phase). The median duration of follow-up was four years; 28 percent of the patients received adjuvant therapy, usually with tamoxifen (n = 83). A multivariate analysis based on complete data on 250 patients included the following covariates: age (greater than or equal to 75, 50 to 74, and less than or equal to 49 years), tumor size (less than or equal to 20 vs. greater than 20 mm), concentration of estrogen and progesterone receptors (less than 10 vs. greater than or equal to 10 fmol per milligram of protein), ploidy (diploid vs. nondiploid), and S-phase category (fraction of cells in S phase: less than 7.0 percent, 7.0 to 11.9 percent, and greater than or equal to 12 percent). The S-phase fraction yielded the most prognostic information, followed by progesterone-receptor status and tumor size. A prognostic model based on these three variables identified 37 percent of the patients as constituting a high-risk group with a fourfold increased risk of distant recurrence. In the remaining 63 percent of the patients, the five-year overall survival rate (92 +/- 4 [+/- SE] percent) did not differ from the expected age-adjusted rate for Swedish women. We conclude that a prognostic index that includes indicators of the proliferative activity of tumor cells may be able to identify women with node-negative breast cancer in whom the risk of recurrence is sufficiently low that adjuvant chemotherapy can be avoided.
肿瘤细胞增殖活性的检测指标对淋巴结阴性乳腺癌患者具有预后价值。我们研究了瑞典南部367例接受此类癌症手术切除的女性。对肿瘤标本进行DNA流式细胞术分析，以评估DNA含量（倍体性）和细胞周期合成期（S期）细胞的比例。随访的中位时间为4年；28%的患者接受辅助治疗，通常使用他莫昔芬（n = 83）。基于250例患者的完整数据进行的多变量分析纳入了以下协变量：年龄（大于或等于75岁、50至74岁和小于或等于49岁）、肿瘤大小（小于或等于20 mm与大于20 mm）、雌激素和孕激素受体浓度（小于10 fmol/mg蛋白质与大于或等于10 fmol/mg蛋白质）、倍体性（二倍体与非二倍体）以及S期类别（S期细胞比例：小于7.0%、7.0%至11.9%和大于或等于12%）。S期比例提供了最多的预后信息，其次是孕激素受体状态和肿瘤大小。基于这三个变量的预后模型确定37%的患者构成高风险组，远处复发风险增加四倍。在其余63%的患者中，五年总生存率（92±4[±SE]%）与瑞典女性预期的年龄调整率无差异。我们得出结论，一个包含肿瘤细胞增殖活性指标的预后指数可能能够识别出淋巴结阴性乳腺癌患者中复发风险足够低、可避免辅助化疗的女性。
