Baildam A D, Zaloudik J, Howell A, Barnes D M, Moore M, Sellwood R A
Br J Cancer. 1987 May;55(5):561-6. doi: 10.1038/bjc.1987.114.
The effect of tamoxifen upon cellular DNA ploidy in carcinoma of the breast was assessed by flow cytometry (FCM), in a prospective group of 77 patients with primary operable disease. Each had a needle biopsy at the outpatient visit for diagnosis and FCM analysis, and definitive surgery was performed a median of 8 days later. Forty received tamoxifen during this period - 40 mg qds loading dose for 24 h, followed by 20 mg daily until the day of operation: 37 patients received no therapy. The DNA histogram from the needle biopsy was compared with that obtained from the resected tumour for each individual. There was little change between the pair of histograms from tumours from the untreated patients. In those who had received tamoxifen the most consistent effect was a marked reduction in the magnitude of the 'tetraploid' peak in tetraploid or near-tetraploid tumours with DNA indices 1.8-2.0. There was little change in diploid or 'other DNA-aneuploid' tumours. In tetraploid tumours (DNA index of 2.0) the percentage of nuclei in the diploid S phase was significantly related to the percentage of nuclei in the diploid G2 + M/tetraploid G1 peak (P less than 0.003, unpaired t test). These data suggest that an effect of tamoxifen can be demonstrated by FCM upon tumours exhibiting a tetraploid or near-tetraploid DNA content. It is possible that tetraploid or near-tetraploid human mammary tumours may be a distinct group of endocrine responsive tumours within the overall group of aneuploid tumours, and that the majority are probably derived from the diploid population rather than being a true aneuploid population.
通过流式细胞术(FCM)对77例原发性可手术乳腺癌患者进行前瞻性研究,评估他莫昔芬对乳腺癌细胞DNA倍体的影响。每位患者在门诊就诊时进行针吸活检以进行诊断和FCM分析,中位8天后进行根治性手术。在此期间,40例患者接受他莫昔芬治疗——24小时内给予40mg每日四次的负荷剂量,随后每日20mg直至手术日;37例患者未接受治疗。将每位患者针吸活检的DNA直方图与其切除肿瘤的DNA直方图进行比较。未治疗患者肿瘤的一对直方图之间变化不大。在接受他莫昔芬治疗的患者中,最一致的效果是DNA指数为1.8 - 2.0的四倍体或近四倍体肿瘤中“四倍体”峰的幅度明显降低。二倍体或“其他DNA非整倍体”肿瘤变化不大。在四倍体肿瘤(DNA指数为2.0)中,二倍体S期细胞核百分比与二倍体G2 + M/四倍体G1峰中细胞核百分比显著相关(P < 0.003,非配对t检验)。这些数据表明,通过FCM可以证明他莫昔芬对显示四倍体或近四倍体DNA含量的肿瘤有作用。四倍体或近四倍体人类乳腺肿瘤可能是整个非整倍体肿瘤组中一组独特的内分泌反应性肿瘤,并且大多数可能源自二倍体群体而非真正的非整倍体群体。