Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments.
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments.
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DOI：
10.3390/medsci8010018
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发表时间：
2020-03-23
期刊：
影响因子：
--
通讯作者：
Pelosi, Elvira
中科院分区：
文献类型：
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作者：
Testa, Ugo;Castelli, Germana;Pelosi, Elvira
乳腺癌是女性最常见的癌症。2018年全球新增病例超过200万例。它是西方国家癌症死亡的第二大原因。在分子水平上，乳腺癌是一种异质性疾病，其特征在于由体细胞基因突变、拷贝数改变和染色体结构重排证明的高基因组不稳定性。基因组不稳定性是由DNA损伤修复、转录、DNA复制、端粒维持和有丝分裂染色体分离等缺陷引起的。根据分子特征，乳腺癌根据激素受体（雌激素受体和孕激素受体）、人表皮生长因子受体2（HER 2）和/或BRCA突变的活化而细分为亚型。对原发性和转移性乳腺癌分子特征的深入分析表明，在疾病发展过程中，遗传改变及其克隆进化具有很大的异质性。这些研究有助于确定通过不同突变过程改变的许多致病基因的库。虽然早期乳腺癌在大约70%的患者中是可治愈的疾病，但晚期乳腺癌在很大程度上是不可治愈的。然而，分子研究有助于开发新的治疗方法，靶向HER 2，CDK 4/6，PI 3 K，或涉及聚（ADP-核糖）聚合酶抑制剂的BRCA突变载体和免疫治疗。
Breast cancer is the most commonly occurring cancer in women. There were over two-million new cases in world in 2018. It is the second leading cause of death from cancer in western countries. At the molecular level, breast cancer is a heterogeneous disease, which is characterized by high genomic instability evidenced by somatic gene mutations, copy number alterations, and chromosome structural rearrangements. The genomic instability is caused by defects in DNA damage repair, transcription, DNA replication, telomere maintenance and mitotic chromosome segregation. According to molecular features, breast cancers are subdivided in subtypes, according to activation of hormone receptors (estrogen receptor and progesterone receptor), of human epidermal growth factors receptor 2 (HER2), and or BRCA mutations. In-depth analyses of the molecular features of primary and metastatic breast cancer have shown the great heterogeneity of genetic alterations and their clonal evolution during disease development. These studies have contributed to identify a repertoire of numerous disease-causing genes that are altered through different mutational processes. While early-stage breast cancer is a curable disease in about 70% of patients, advanced breast cancer is largely incurable. However, molecular studies have contributed to develop new therapeutic approaches targeting HER2, CDK4/6, PI3K, or involving poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and immunotherapy.