在全球范围内，乳腺癌的负担不断增加，因为它仍然是女性中最常见的肿瘤，也是癌症相关死亡的第二大原因。乳腺癌是一种异质性疾病，其特征是由BRCA1和BRCA2以及激素受体等关键基因异常引起的不同亚型。然而，即使在每个亚型内部，由潜在的进化机制驱动的异质性被认为是对治疗反应不佳、疾病进展、复发和复发变异性的基础。肿瘤内部异质性突出了肿瘤细胞的可进化性取决于与肿瘤微环境细胞的相互作用。近期高通量测序等筛查技术的进展正揭示肿瘤微环境的复杂性，然而，考虑到肿瘤微环境的潜在生物学和选择性压力对肿瘤细胞可进化性的影响，仍然存在阻碍这些方法实际应用的挑战。在本综述中，我们将重点介绍了迄今为止在定义乳腺癌的分子异质性方面取得的进展及其对诊断、设计和应用靶向治疗以改善临床结果的意义。我们描述了不同的精准诊断和治疗方法及其前景。我们进一步提出，有效的癌症诊断和治疗依赖于揭示肿瘤微环境及其在驱动肿瘤内部异质性方面的作用。在这种异质性背后，达尔文的自然选择概念支撑着，我们认为这些概念需要考虑进来，以确保在治疗决策中具备进化信息。版权所有 © 2023 Xulu，Nweke和Augustine。

The burden of breast cancer continues to increase worldwide as it remains the most diagnosed tumor in females and the second leading cause of cancer-related deaths. Breast cancer is a heterogeneous disease characterized by different subtypes which are driven by aberrations in key genes such as BRCA1 and BRCA2, and hormone receptors. However, even within each subtype, heterogeneity that is driven by underlying evolutionary mechanisms is suggested to underlie poor response to therapy, variance in disease progression, recurrence, and relapse. Intratumoral heterogeneity highlights that the evolvability of tumor cells depends on interactions with cells of the tumor microenvironment. The complexity of the tumor microenvironment is being unraveled by recent advances in screening technologies such as high throughput sequencing; however, there remain challenges that impede the practical use of these approaches, considering the underlying biology of the tumor microenvironment and the impact of selective pressures on the evolvability of tumor cells. In this review, we will highlight the advances made thus far in defining the molecular heterogeneity in breast cancer and the implications thereof in diagnosis, the design and application of targeted therapies for improved clinical outcomes. We describe the different precision-based approaches to diagnosis and treatment and their prospects. We further propose that effective cancer diagnosis and treatment are dependent on unpacking the tumor microenvironment and its role in driving intratumoral heterogeneity. Underwriting such heterogeneity are Darwinian concepts of natural selection that we suggest need to be taken into account to ensure evolutionarily informed therapeutic decisions.Copyright © 2023 Xulu, Nweke and Augustine.