Breast cancer is the quintessential example of how molecular characterization of tumor biology guides therapeutic decisions. From the discovery of the estrogen receptor to current clinical molecular profiles to evolving single cell analytics, the characterization and compartmentalization of breast cancer into divergent subtypes is clear. However, competing with this divergent model of breast cancer is the recognition of intratumoral heterogeneity, which acknowledges the possibility that multiple different subtypes exist within a single tumor. Intratumoral heterogeneity is driven by both intrinsic effects of the tumor cells themselves as well as extrinsic effects from the surrounding microenvironment. There is emerging evidence that these intratumoral molecular subtypes are not static; rather, plasticity between divergent subtypes is possible. Inter-conversion between seemingly different subtypes within a tumor drives tumor progression, metastases, and treatment resistance. Therapeutic strategies must therefore contend with changing phenotypes in an individual patient's tumor. Identifying targetable drivers of molecular heterogeneity may improve treatment durability and disease progression.

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乳腺癌分子亚型的异质性

乳腺癌是肿瘤生物学的分子特征如何指导治疗决策的典型例子。从雌激素受体的发现到目前的临床分子谱，再到不断发展的单细胞分析，乳腺癌的特征和划分为不同的亚型是很清楚的。然而，与这种不同的乳腺癌模型竞争的是对肿瘤内异质性的认识，这承认了单个肿瘤内存在多种不同亚型的可能性。肿瘤内异质性是由肿瘤细胞本身的内在效应和周围微环境的外在效应驱动的。有新的证据表明这些肿瘤内分子亚型不是静态的。相反，不同亚型之间的可塑性是可能的。肿瘤内看似不同的亚型之间的相互转换驱动肿瘤进展、转移和治疗抗性。因此，治疗策略必须应对个体患者肿瘤中不断变化的表型。确定分子异质性的可靶向驱动因素可能会提高治疗的持久性和疾病进展。