Next-generation sequencing has sparked the exploration of cancer genomes, with the aim of discovering the genetic etiology of the disease and proposing rationally designed therapeutic interventions. Driver gene alterations have been comprehensively charted, but the improvement of cancer patient management somewhat lags behind these basic breakthroughs. Recently, large-scale sequencing that focused on metastasis, the main cause of cancer-related deaths, has shed new light on the driving forces at work during disease progression, particularly in breast cancer. Despite a fairly stable pool of driver genetic alterations between early and late disease, a number of therapeutically targetable mutations have been found enriched in metastatic samples. The molecular processes fueling disease progression have been delineated in recent studies and the clonal composition of breast cancer samples can be examined in detail. Here we discuss how these findings may be combined to improve the diagnosis of breast cancer to better select patients at risk, and to identify targeted agents to treat advanced diseases and to design therapeutic strategies exploiting vulnerabilities of cancer cells rooted in their ability to evolve and drive disease progression.

中文翻译：

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癌症分子亚型和治疗对转移性乳腺癌突变谱的影响。

下一代测序已激发了对癌症基因组的探索，目的是发现疾病的遗传病因并提出合理设计的治疗干预措施。驱动基因的改变已被全面绘制，但癌症患者管理的改善在一定程度上落后于这些基本突破。最近，专注于转移的大规模测序，转移是癌症相关死亡的主要原因，在疾病进展期间，特别是在乳腺癌中，为工作的驱动力提供了新的思路。尽管在早期和晚期疾病之间有相当稳定的驾驶员遗传变化，但是发现许多可治疗靶向的突变富含转移样品。在最近的研究中已经描述了促进疾病发展的分子过程，并且可以详细检查乳腺癌样品的克隆组成。在这里，我们讨论了如何结合这些发现来改善乳腺癌的诊断，以更好地选择处于风险中的患者，并确定靶向药物以治疗晚期疾病，并设计利用癌细胞脆弱性而发展的治疗策略，这些脆弱性源于癌细胞的进化和驱动能力疾病进展。