Sandro Pitigliani Medical Oncology Unit, Department of Oncology, Hospital of Prato, Istituto Toscano Tumori, Piazza Ospedale 2, 59100 Prato, Italy.
Nat Rev Clin Oncol. 2010 Dec;7(12):725-32. doi: 10.1038/nrclinonc.2010.170. Epub 2010 Oct 26.
Recommendation of systemic adjuvant therapy and choice of optimal agents for early-stage breast cancer remains a challenge. Adjuvant therapy is indicated on the assumption of residual micrometastatic disease. Adjuvant assessment tools for prognosis and prediction of treatment benefit, including Adjuvant! Online, the St Gallen Consensus, Oncotype DX(®) and MammaPrint(®), aid clinical decision making. However, all of these tools have limitations that must be considered in their judicious application. Clinicopathological based tools are critically dependent on accurate, standardized measurement of parameters. Multigene tools are appealing for their objectivity and reproducibility, particularly regarding analysis of proliferation, but these approaches still overlook the biological heterogeneity within tumors evidenced by distinct cell subpopulations with different genomic patterns and function. The greatest treatment challenge remains for patients assessed as intermediate risk of relapse, a problem not overcome by multigene tools. Remarkable diversity in breast cancer dictates that adjuvant management must be biologically driven. Future identification of predictive biomarkers for specific chemotherapy sensitivity may allow targeted use of available agents, including anthracyclines, taxanes and DNA damaging agents. The presence of drug targets and targetable signaling pathways, rather than molecularly defined subgroups, may ultimately drive treatment decisions.
早期乳腺癌的系统辅助治疗推荐和最佳药物选择仍然是一个挑战。辅助治疗是基于残留微转移疾病的假设。辅助预后评估工具和治疗获益预测工具，包括 Adjuvant! Online、圣加仑共识、Oncotype DX(®) 和 MammaPrint(®)，有助于临床决策。然而，所有这些工具都有局限性，在明智地应用时必须考虑这些局限性。基于临床病理的工具严重依赖于参数的准确、标准化测量。多基因工具因其客观性和可重复性而具有吸引力，特别是在分析增殖方面，但这些方法仍然忽略了肿瘤内的生物学异质性，表现为不同的细胞亚群具有不同的基因组模式和功能。对于被评估为复发风险中等的患者来说，最大的治疗挑战仍然存在，而多基因工具并不能解决这个问题。乳腺癌的显著多样性表明，辅助管理必须具有生物学驱动性。未来可能会发现针对特定化疗敏感性的预测生物标志物，从而可以有针对性地使用现有的药物，包括蒽环类药物、紫杉烷类药物和 DNA 损伤剂。药物靶点和可靶向信号通路的存在，而不是分子定义的亚群，可能最终会驱动治疗决策。
