Background/Objectives:BRCA1pathogenic variant (PV)-associated breast cancers are most commonly seen in hereditary genetic conditions such as the autosomal-dominant Hereditary Breast and Ovarian Cancer (HBOC) syndrome, and rarely in sporadic breast cancer. Such breast cancers tend to exhibit greater aggressiveness and poorer prognoses due to the influence ofBRCA1pathogenic variants (PVs) on the tumour microenvironment. Additionally, while the genetic basis ofBRCA1PV breast cancer is well-studied, the role of epigenetic mediators in the tumourigenesis of these hereditary breast cancers is also worth exploring.Results: PVs in theBRCA1gene interact with stromal cells and immune cells, promoting epithelial–mesenchymal transition, angiogenesis, and affecting oestrogen levels. Additionally,BRCA1PVs contribute to breast cancer development through epigenetic effects on cells, including DNA methylation and histone acetylation, leading to the suppression of proto-oncogenes and dysregulation of cytokines. In terms of epigenetics, lysine-specific demethylase 1 (LSD-1) is considered a master epigenetic regulator, governing both transcriptional repression and activation. It exerts epigenetic control overBRCA1and, to a lesser extent,BRCA2genes. The upregulation of LSD-1 is generally associated with a poorer prognosis in cancer patients. In the context of breast cancer inBRCA1/2PV carriers, LSD-1 contributes to tumour development through various mechanisms. These include the maintenance of a hypoxic environment and direct suppression ofBRCA1gene expression.Conclusions: While LSD-1 itself does not directly cause mutations inBRCA1orBRCA2genes, its epigenetic influence sheds light on the potential role of LSD-1 inhibitors as a therapeutic approach in managing breast cancer, particularly in individuals withBRCA1/2PVs. Targeting LSD-1 may help counteract its detrimental effects and provide a promising avenue for therapy in this specific subgroup of breast cancer.
背景/目的：BRCA1致病性变异（PV）相关乳腺癌最常见于遗传性基因疾病，如常染色体显性遗传的遗传性乳腺癌和卵巢癌（HBOC）综合征，在散发性乳腺癌中较为罕见。由于BRCA1致病性变异对肿瘤微环境的影响，此类乳腺癌往往表现出更强的侵袭性和更差的预后。此外，尽管BRCA1 PV乳腺癌的遗传基础已得到充分研究，但表观遗传介质在这些遗传性乳腺癌肿瘤发生中的作用也值得探讨。结果：BRCA1基因中的PV与基质细胞和免疫细胞相互作用，促进上皮-间质转化、血管生成并影响雌激素水平。此外，BRCA1 PV通过对细胞的表观遗传效应（包括DNA甲基化和组蛋白乙酰化）促进乳腺癌发展，导致原癌基因抑制和细胞因子失调。在表观遗传学方面，赖氨酸特异性去甲基化酶1（LSD-1）被认为是主要的表观遗传调控因子，控制转录抑制和激活。它对BRCA1基因（在较小程度上对BRCA2基因）施加表观遗传控制。LSD-1的上调通常与癌症患者较差的预后相关。在BRCA1/2 PV携带者的乳腺癌背景下，LSD-1通过多种机制促进肿瘤发展，包括维持缺氧环境和直接抑制BRCA1基因表达。结论：虽然LSD-1本身不直接导致BRCA1或BRCA2基因突变，但其表观遗传影响揭示了LSD-1抑制剂作为治疗乳腺癌（特别是在BRCA1/2 PV携带者中）的潜在作用。靶向LSD-1可能有助于抵消其有害影响，并为这一特定亚型乳腺癌的治疗提供有前景的途径。
肿瘤(癌症)患者之家