Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Cancer. 2011 May 1;2:232-61. doi: 10.7150/jca.2.232.
Understanding of the biology and clinical behavior of ductal carcinoma in situ (DCIS) is currently inadequate. The aim of this comprehensive review was to identify important molecular biological markers associated with DCIS and candidate markers associated with increased risk of ipsilateral recurrence after diagnosis of DCIS. A comprehensive systematic review was performed to identify studies published in the past 10 years that investigated biological markers in DCIS. To be included in this review, studies that investigated the rate of biological expression of markers had to report on at least 30 patients; studies that analyzed the recurrence risk associated with biomarker expression had to report on at least 50 patients. There were 6,252 patients altogether in our review. Biological markers evaluated included steroid receptors, proliferation markers, cell cycle regulation and apoptotic markers, angiogenesis-related proteins, epidermal growth factor receptor family receptors, extracellular matrix-related proteins, and COX-2. Although the studies in this review provide valuable preliminary information regarding the expression and prognostic significance of biomarkers in DCIS, common limitations of published studies (case-series, cohort, and case-control studies) were that they were limited to small patient cohorts in which the extent of surgery and use of radiotherapy or endocrine therapy varied from patient to patient, and variable methods of determining biomarker expression. These constraints made it difficult to interpret the absolute effect of expression of various biomarkers on risk of local recurrence. No prospective validation studies were identified. As the study of biomarkers are in their relative infancy in DCIS compared with invasive breast cancer, key significant prognostic and predictive markers associated with invasive breast cancer have not been adequately studied in DCIS. There is a critical need for prospective analyses of novel and other known breast cancer molecular markers in large cohorts of patient with DCIS to differentiate indolent from aggressive DCIS and better tailor the need and extent of current therapies.
对导管原位癌 (DCIS) 的生物学和临床行为的理解目前还不够充分。本综述的目的是确定与 DCIS 相关的重要分子生物学标志物，以及与 DCIS 诊断后同侧复发风险增加相关的候选标志物。进行了全面的系统评价，以确定过去 10 年中研究 DCIS 中生物标志物的研究。要包括在本综述中，研究生物标志物生物学表达率的研究必须至少报告 30 例患者；分析与生物标志物表达相关的复发风险的研究必须至少报告 50 例患者。我们的综述共包括 6252 例患者。评估的生物学标志物包括甾体受体、增殖标志物、细胞周期调节和凋亡标志物、血管生成相关蛋白、表皮生长因子受体家族受体、细胞外基质相关蛋白和 COX-2。尽管本综述中的研究提供了关于 DCIS 中生物标志物表达和预后意义的有价值的初步信息，但已发表研究的常见局限性（病例系列、队列和病例对照研究）是，它们仅限于小患者队列，其中手术范围和放疗或内分泌治疗的使用因患者而异，并且生物标志物表达的测定方法也不同。这些限制使得难以解释各种生物标志物表达对局部复发风险的绝对影响。没有发现前瞻性验证研究。由于与浸润性乳腺癌相比，DCIS 中生物标志物的研究仍处于相对初期阶段，因此与浸润性乳腺癌相关的关键重要预后和预测标志物尚未在 DCIS 中得到充分研究。迫切需要对 DCIS 中具有侵袭性的新型和其他已知乳腺癌分子标志物进行前瞻性分析，以区分惰性和侵袭性 DCIS，并更好地针对当前疗法的需求和范围进行调整。
