Singletary E, Lieberman R, Atkinson N, Sneige N, Sahin A, Tolley S, Colchin M, Bevers T, Stelling C, Fornage B, Fritsche H, Hittelman W, Kelloff G, Lippman S M
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Cancer Epidemiol Biomarkers Prev. 2000 Oct;9(10):1087-90.
Surrogate end point biomarkers for risk assessment and efficacy of potential chemopreventive agents are needed to improve the efficiency and reduce the cost of chemoprevention trials. It is imperative to develop the best clinical breast model for translational surrogate end point biomarker studies, especially with respect to accrual feasibility. We have initiated a prospective study to develop biomarkers for tamoxifen and N-[4-hydroxyphenyl] retinamide by administering either a placebo or both drugs for 2-4 weeks to women with ductal carcinoma in situ or early invasive cancers in the interval between the initial diagnostic core biopsy and definitive surgery. The principle end point is pretreatment versus posttreatment tumor levels of Ki-67; a number of other exploratory markers will also be examined. The planned target sample size is 100 patients. Between February 1997 and February 2000, 4514 women who had either an abnormal mammogram or a diagnosed breast cancer were screened for the study. Of these 4514 screened patients, 52 (1%) were registered on the study. Major factors of nonparticipation in the remaining 4462 women were as follows: (a) no evidence of malignancy (2081 patients; 46%); (b) ineligible per protocol criteria (575 patients; 13%); (c) preoperative chemotherapy/tamoxifen (520 patients; 11%); (d) surgery scheduling conflict (360 patients; 8%); (e) outside needle biopsy (221 patients; 5%); (f) no residual disease after excisional biopsy (345 patients; 8%); and (g) second opinion only (123 patients; 3%). Other nonparticipation factors included fine needle aspiration only, refusal, tumor size > 2 cm, and estrogen replacement therapy (35 patients each; 2% each). The protocol was amended in midstudy to allow outside needle biopsy, tumor > 2 cm, and estrogen replacement therapy. Accrual to biomarker (nontherapeutic) protocols with delay in definitive cancer surgery is challenging but feasible. Although some accrual problems remain, we have nonetheless succeeded in recruiting 50% of our target sample size in a 3-year period.
为提高化学预防试验的效率并降低成本，需要用于潜在化学预防药物风险评估和疗效的替代终点生物标志物。开发用于转化替代终点生物标志物研究的最佳临床乳腺模型势在必行，尤其是在入组可行性方面。我们已启动一项前瞻性研究，通过向导管原位癌或早期浸润性癌患者在初始诊断性核心活检和确定性手术之间的间隔期给予安慰剂或两种药物2 - 4周，来开发他莫昔芬和N - [4 - 羟基苯基]视黄酰胺的生物标志物。主要终点是Ki - 67的治疗前与治疗后肿瘤水平；还将检查许多其他探索性标志物。计划的目标样本量为100名患者。在1997年2月至2000年2月期间，对4514名乳房X线摄影异常或已诊断为乳腺癌的女性进行了该研究的筛查。在这4514名筛查患者中，52名（1%）登记参加了该研究。其余4462名女性未参与的主要因素如下：（a）无恶性证据（2081名患者；46%）；（b）不符合方案标准（575名患者；13%）；（c）术前化疗/他莫昔芬（520名患者；11%）；（d）手术安排冲突（360名患者；8%）；（e）外部针吸活检（221名患者；5%）；（f）切除活检后无残留疾病（345名患者；8%）；以及（g）仅寻求第二种意见（123名患者；3%）。其他未参与因素包括仅细针穿刺抽吸、拒绝、肿瘤大小>2 cm和雌激素替代疗法（各35名患者；各2%）。该方案在研究中期进行了修订，以允许外部针吸活检、肿瘤>2 cm和雌激素替代疗法。入组确定性癌症手术延迟的生物标志物（非治疗性）方案具有挑战性但可行。尽管仍存在一些入组问题，但我们在3年时间内成功招募了目标样本量的50%。
