Breast cancer is the second leading cause of mortality among women worldwide. Despite the available therapeutic regimes, variable treatment response is reported among different breast cancer subtypes. Recently, the effects of the tumor microenvironment on tumor progression as well as treatment responses have been widely recognized. Hypoxia and hypoxia inducible factors in the tumor microenvironment have long been known as major players in tumor progression and survival. However, the majority of our understanding of hypoxia biology has been derived from two dimensional (2D) models. Although many hypoxia-targeted therapies have elicited promising results in vitro and in vivo, these results have not been successfully translated into clinical trials. These limitations of 2D models underscore the need to develop and integrate three dimensional (3D) models that recapitulate the complex tumor-stroma interactions in vivo. This review summarizes role of hypoxia in various hallmarks of cancer progression. We then compare traditional 2D experimental systems with novel 3D tissue-engineered models giving accounts of different bioengineering platforms available to develop 3D models and how these 3D models are being exploited to understand the role of hypoxia in breast cancer progression.

乳腺癌是全球女性死亡的第二大原因。尽管有可用的治疗方案，但在不同的乳腺癌亚型中报告了不同的治疗反应。最近，肿瘤微环境对肿瘤进展和治疗反应的影响已得到广泛认可。长期以来，肿瘤微环境中的缺氧和缺氧诱导因子被认为是肿瘤进展和生存的主要参与者。然而，我们对缺氧生物学的大部分理解来自二维 (2D) 模型。尽管许多针对缺氧的疗法在体外和体内都取得了可喜的成果，这些结果尚未成功转化为临床试验。2D 模型的这些局限性强调了开发和整合 3D (3D) 模型的必要性，这些模型概括了体内复杂的肿瘤-基质相互作用。本综述总结了缺氧在癌症进展的各种标志中的作用。然后，我们将传统 2D 实验系统与新型 3D 组织工程模型进行比较，说明可用于开发 3D 模型的不同生物工程平台，以及如何利用这些 3D 模型来了解缺氧在乳腺癌进展中的作用。