Kaklamani Virginia
Department of Medicine, Division of Hematology/Oncology, Feinberg School of Medicine of Northwestern University 676 North St. Clair Street, Suite 850, Chicago, IL, USA.
Expert Rev Mol Diagn. 2006 Nov;6(6):803-9. doi: 10.1586/14737159.6.6.803.
We now recognize that not all breast cancers are the same. Different characteristics in gene expression profiles result in differential clinical behavior. With the use of gene microarrays, different subtypes of breast cancer have been characterized. These subtypes include the basal, the ERBB2+, and the luminal A, B and C subtypes. The importance of these different subtypes lies in the fact that they differ in clinical outcome, with the basal and ERBB2+ subtypes having the worst prognosis and the luminal A group having the best prognosis. However, identification of these subtypes is still not clinically used. Other strategies for evaluating tumors in a clinical setting have been developed using smaller sets of genes. One such strategy is the 21-gene assay (Oncotype DX), which is currently in commercial use in the USA. One advantage of this test is the use of paraffin-embedded blocks instead of previous methods, which required fresh frozen tissue. Oncotype DX has been shown to predict 10-year distant recurrence in patients with estrogen receptor-positive, axillary lymph node-negative breast cancer. This genomic assay has also been shown to predict chemotherapy and endocrine therapy response. Large, prospective, randomized clinical trials are currently underway using this genomic test. Other similar tests are also finding their way in clinical practice. A 70-gene assay, which has been developed by a group in The Netherlands, is currently being used as a tool to assign treatment in women with early stage breast cancer. In the near future, clinical decisions will most likely be dictated by the genetic characteristics of the tumor, with the clinical characteristics becoming less important. Tailoring our treatment based on individual tumor characteristics will help us develop better therapeutic strategies and save many of our patients from receiving unnecessary toxic therapy.
我们现在认识到,并非所有乳腺癌都是相同的。基因表达谱中的不同特征导致了不同的临床行为。通过使用基因微阵列,已对乳腺癌的不同亚型进行了特征描述。这些亚型包括基底样、ERBB2+以及管腔A型、B型和C型。这些不同亚型的重要性在于它们在临床结果上存在差异,其中基底样和ERBB2+亚型的预后最差,而管腔A型的预后最好。然而,这些亚型的识别在临床上仍未得到应用。在临床环境中,已开发出使用较少基因集来评估肿瘤的其他策略。一种这样的策略是21基因检测(Oncotype DX),目前在美国已投入商业使用。该检测的一个优点是使用石蜡包埋块,而不是以前需要新鲜冷冻组织的方法。Oncotype DX已被证明可预测雌激素受体阳性、腋窝淋巴结阴性乳腺癌患者的10年远处复发情况。这种基因组检测也已被证明可预测化疗和内分泌治疗反应。目前正在使用这种基因组检测进行大型、前瞻性、随机临床试验。其他类似检测也正在进入临床实践。由荷兰的一个团队开发的一种70基因检测,目前正被用作早期乳腺癌女性患者治疗分配的工具。在不久的将来,临床决策很可能由肿瘤的基因特征决定,而临床特征的重要性将降低。根据个体肿瘤特征量身定制我们的治疗方法,将有助于我们制定更好的治疗策略,并使许多患者避免接受不必要的毒性治疗。