Breast cancer (BC) remains a clinical challenge despite improved treatments and public awareness to ensure early diagnosis. A major issue is the ability of BC cells (BCCs) to survive as dormant cancer cells in the bone marrow (BM), resulting in the cancer surviving for decades with the potential to resurge as metastatic cancer. The experimental evidence indicates similarity between dormant BCCs and other stem cells, resulting in the preponderance of data to show dormant BCCs being cancer stem cells (CSCs). The BM niche and their secretome support BCC dormancy. Lacking in the literature is a comprehensive research to describe how the hypoxic environment within the BM may influence the behavior of BCCs. This information is relevant to understand the prognosis of BC in young and aged individuals whose oxygen levels differ in BM. This review discusses the changing information on vascularity in different regions of the BM and the impact on endogenous hematopoietic stem cells (HSCs). This review highlights the necessary information to provide insights on vascularity of different BM regions on the behavior of BCCs, in particular a dormant phase. For instance, how the transcription factor HIF1-α (hypoxia-inducible factor 1 alpha), functioning as first responder under hypoxic conditions, affects the expression of specific gene networks involved in energy metabolism, cell survival, tumor invasion and angiogenesis. This enables cell fate transition and facilitates tumor heterogeneity, which in turn favors tumor progression and resistance to anticancer treatments Thus, HIF1-α could be a potential target for cancer treatment. This review describes epigenetic mechanisms involved in hypoxic responses during cancer dormancy in the bone marrow. The varied hypoxic environment in the BM is relevant to understand the complex process of the aging bone marrow for insights on breast cancer outcome between the young and aged.

尽管改善了治疗方法并提高了公众的意识以确保早期诊断，但乳腺癌（BC）仍然是临床挑战。一个主要问题是BC细胞（BCC）作为休眠的癌细胞在骨髓（BM）中存活的能力，导致该癌症存活了数十年，并有可能复发为转移性癌症。实验证据表明，休眠的BCC与其他干细胞之间具有相似性，导致大量数据表明休眠的BCC是癌症干细胞（CSC）。BM小生境及其分泌组支持BCC休眠。缺乏文献是一项全面的研究，以描述BM内的低氧环境如何影响BCC的行为。此信息与了解BM中氧水平不同的年轻和老年个体的BC预后有关。这篇综述讨论了有关BM不同区域血管变化的信息以及对内源性造血干细胞（HSC）的影响。这篇综述着重介绍了必要的信息，以提供有关不同BM区域的血管性，对BCC行为（尤其是休眠阶段）的见解。例如，在缺氧条件下，转录因子HIF1-α（低氧诱导因子1α）如何作为第一反应者，如何影响涉及能量代谢，细胞存活，肿瘤侵袭和血管生成的特定基因网络的表达。这使细胞命运转变并促进肿瘤异质性，进而有利于肿瘤进展和对抗癌治疗的抗性。因此，HIF1-α可能成为癌症治疗的潜在靶标。这篇综述描述了骨髓在癌症休眠期间参与低氧反应的表观遗传机制。BM中不同的缺氧环境与了解衰老的骨髓的复杂过程有关，以了解年轻人和老年人之间乳腺癌的结局。