Department of Pathology and Laboratory Medicine, Program in Translational Medicine, UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Department of Pathology and Laboratory Medicine, Program in Translational Medicine, UNC Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Am J Pathol. 2013 Oct;183(4):1113-1124. doi: 10.1016/j.ajpath.2013.08.002. Epub 2013 Aug 27.
Breast cancer is noted for disparate clinical behaviors and patient outcomes, despite common histopathological features at diagnosis. Molecular pathogenesis studies suggest that breast cancer is a collection of diseases with variable molecular underpinnings that modulate therapeutic responses, disease-free intervals, and long-term survival. Traditional therapeutic strategies for individual patients are guided by the expression status of the estrogen and progesterone receptors (ER and PR) and human epidermal growth factor receptor 2 (HER2). Although such methods for clinical classification have utility in selection of targeted therapies, short-term patient responses and long-term survival remain difficult to predict. Molecular signatures of breast cancer based on complex gene expression patterns have utility in prediction of long-term patient outcomes, but are not yet used for guiding therapy. Examination of the correspondence between these methods for breast cancer classification reveals a lack of agreement affecting a significant percentage of cases. To realize true personalized breast cancer therapy, a more complete analysis and evaluation of the molecular characteristics of the disease in the individual patient is required, together with an understanding of the contributions of specific genetic and epigenetic alterations (and their combinations) to management of the patient. Here, we discuss the molecular and cellular heterogeneity of breast cancer, the impact of this heterogeneity on practical breast cancer classification, and the challenges for personalized breast cancer treatment.
乳腺癌具有明显不同的临床行为和患者预后，尽管在诊断时具有共同的组织病理学特征。分子发病机制研究表明，乳腺癌是一组具有不同分子基础的疾病，这些基础可以调节治疗反应、无病间隔和长期生存。个体患者的传统治疗策略是根据雌激素和孕激素受体（ER 和 PR）以及人表皮生长因子受体 2（HER2）的表达状态来指导。尽管这些临床分类方法在选择靶向治疗方面具有实用性，但短期患者反应和长期生存仍然难以预测。基于复杂基因表达模式的乳腺癌分子特征在预测长期患者结局方面具有实用性，但尚未用于指导治疗。对这些乳腺癌分类方法之间的一致性进行检查，发现存在影响大量病例的不一致性。为了实现真正的个体化乳腺癌治疗，需要对个体患者的疾病分子特征进行更全面的分析和评估，并了解特定遗传和表观遗传改变（及其组合）对患者管理的贡献。在这里，我们讨论了乳腺癌的分子和细胞异质性，这种异质性对实用乳腺癌分类的影响，以及对个体化乳腺癌治疗的挑战。
