乳腺癌

At AstraZeneca our aim is to help improve the outcomes of br东 癌症 patients with the ambition to one day eliminate 癌症 as a cause of death. 纵观澳门葡京赌博游戏的历史, our innovative science has led to potential practice-changing medicines for patients with br东 癌症, 尽管澳门葡京赌博游戏已经走了这么远, 还有很多工作要做. We are committed to furthering our research to redefine the br东 癌症 treatment paradigm.

乳腺癌仍然是世界上最常见的女性癌症¹ 也是女性癌症死亡的主要原因.² Men are susceptible to br东 癌症, although at a far lower rate than women.³ 它可以从器官的各个部位开始, 包括管道, 小叶(产生牛奶), 或者是中间的组织.⁴

在过去的50年里，乳腺癌的治疗已经发生了变化⁵澳门葡京赌博游戏很自豪能够通过研究持续支持这一项目.

介绍乳房切除术(一种切除整个乳房的手术)⁶)和化疗进入临床实践, 以及筛查和诊断的进步, 即乳房x光检查, 和 increased disease awareness have significantly improved the survival of people living with br东 癌症.^4,7

随着分子生物学的进步, 系统生物学和基因组科学, 澳门葡京赌博游戏已经从细胞层面扩展了对乳腺癌的认识, 分子和基因组水平.⁴ 澳门葡京赌博游戏现在知道了 br东 癌症 is one of the most biologically diverse tumour types with various factors fuelling its development 和 progression.⁴

Today we can classify 和 help to treat those living with br东 癌症 by their 激素受体 or HER2表达状况，以及他们是否有 BRCA突变. But as our underst和ing of the different factors fuelling br东 癌症 grows, so will our ability to develop potential medicines for new subtypes of patients.

帮助确定乳腺癌的最佳治疗方法, it is critical to identify key receptors or proteins that may be driving the tumour growth. The expression of receptors or proteins in turn determines how the br东 癌症 is classified.

乳腺癌分类-激素受体

激素是乳腺组织发育的驱动因素, so it’s no surprise they also play a critical role in the development of 癌症ous tissue in the br东s as well - in fact, 一个多世纪以来，它们在肿瘤形成中的作用已经得到了充分的记录.⁸ The growth 和 proliferation of female br东 tissue occurs during puberty when hormonal stimulation triggers cellular differentiation. The changes in puberty are heavily influenced by the steroid hormones, oestrogen⁸ 和孕激素, which act as the ‘master regulators’ of the development of regular functions of the br东s.⁹

这两种类固醇激素与细胞受体结合，刺激细胞生长. 不幸的是, this exact mechanism is exploited by tumour cells which also use oestrogen 和孕激素 to fuel their growth.¹⁰

The presence of oestrogen receptors (ER) 和/or progesterone receptors (PR) on tumour cells is used as one of the main classification methods of br东 癌症. 标记为激素受体(HR)阳性, 超过1%的乳腺癌细胞必须表达ER, 或两个.¹¹ The 癌症 is labelled as 激素受体 (HR)-negative when less than 1% possess these receptors¹¹ (如果有受体的话)，它不太可能是肿瘤生长的原因.¹²

激素在乳腺癌中的作用已经被很好地理解了一段时间, 和 as a result some of the first medicines designed 具体地说 for br东 癌症 were hormone therapies.¹⁰ These therapies prevent the 癌症 cells from using oestrogen or progesterone 和 can work in various ways.

Oestrogen receptors are far more prevalent than progesterone receptors in br东 癌症, with approximately 80% of all br东 癌症s being hormone-dependent 和 oestrogen receptor-positive (ER+).¹³ Cases of tumours being oestrogen receptor-negative/progesterone receptor-positive (ER-/PR+) are extremely rare¹⁴ 和, 因此, treatments often target pathways involving oestrogen – these are often called endocrine inhibitors^.15

指导治疗意见的作用: 芳香酶抑制剂(AIs), 例如, prevent oestrogen from being produced by certain tissues (other than the ovaries), while other therapies known as selective oestrogen receptor modulators (SERMs) compete with oestrogen to bind to receptor, 从而阻断雌激素的作用.¹⁵

Another method of targeting HR+ br东 癌症 is to selectively degrade the oestrogen receptor with the use of selective oestrogen receptor degraders (SERDs).¹⁶ 通过降解雌激素受体, the ER signalling pathway is broken 和 the 癌症 cells ability to use oestrogen is snatched away. serd常用于转移性疾病¹⁷ - w在这里 the 癌症 has spread to other parts of the body - 和 are increasingly used in combinations with other agents to potentially overcome resistance to endocrine therapies.^18,19

The number of medicines available for HR+ br东 癌症 has continued to grow in the past few decades, 但仍有更多工作要做. Now we are striving to further transform the lives of women with HR+ disease by building on our rich heritage.

乳腺癌分类- HER2受体

在80年代早期, 人表皮生长因子2 (HER2)基因, 哪些有助于维持健康的细胞生命周期, was found to fuel excessive 癌症 cell growth 和 proliferation in br东 癌症 cells when t在这里 is overexpression of the HER2 gene or protein.²⁰

High levels of HER2 protein expression is found in approximately 20% of br东 癌症s 和 is associated with aggressive 和 fast-growing disease.¹³

乳腺癌分类- BRCA突变

Developments within 基因组学 identified further biomarkers which can be actioned to target br东 癌症, 具体地说, 这两个 BR东 CA癌症易感性(BRCA)基因- BRCA1和BRCA2.²⁶

The two BRCA genes are considered ‘tumour suppressors’ 和 repair damage caused to our DNA in a process known as the DNA Damage Response (DDR), 特别是同源重组修复(HRR), 哪一种只是实现这一目标的途径之一呢. 值得注意的是，这也是DDR的一部分, a family of enzymes known as PARPs (Poly(ADP-Ribose) Polymerases) helps to repair damage through another pathway.²⁷

当BRCA基因发生突变时, they cannot perform their function 和 the risk of developing 癌症 increases.²⁸ 平均, a woman with a BRCA1 or BRCA2 gene mutation has up to a 7 in 10 chance of acquiring br东 癌症 by age 80.²⁹

在指导治疗方案方面的作用: 在细胞水平上, 突变的BRCA基因导致HRR通路功能失调并存活, 细胞必须依靠其他途径. 这是可以通过靶向治疗来利用的. PARP inhibitors trap the PARP enzyme 和 prevent single-str和ed DNA breaks from being repaired. 这导致双链DNA断裂的增加, 无法通过功能失调的HRR通路修复. 细胞, then must rely on a back-up pathway that is less accurate 和 prone to error at which point the level of DNA damage goes beyond the manageable limit 和 leads to 癌症 cell death.³⁰

AstraZeneca is committed to investigating the potential of DDR inhibition in br东 癌症. 了解更多关于DDR的信息, including other molecules involved 和 how inhibition of DDR pathways can results in a targeted treatment approach, 点击 在这里.

To truly succeed in reaching our goal of eliminating 癌症 as a cause of death we must change the practice of medicine.

40多年来, 澳门葡京网赌游戏为乳腺癌治疗的进步做出了贡献, 拥有一系列开创性的药物, 包括有针对性的单一疗法和精确/个性化的组合, which continue to have a critical role in improving outcomes for women with br东 癌症.

乳腺癌仍然是澳门葡京网赌游戏的重点. 随着澳门葡京赌博游戏对这种复杂肿瘤类型的特征的理解不断加深, the way we classify br东 癌症 和 the way we treat will undoubtedly change, 这是澳门葡京赌博游戏在澳门葡京网赌游戏率先做的. We are leading an exciting phase of scientific discovery 和 innovation 和 are identifying novel ways of improving outcomes for patient populations which are associated with poor clinical outcomes. We continue to strive for improved testing to identify the actionable targets of an individual’s br东 癌症 和 bring the benefits of a biomarker-driven approach to even more patients

帮助解决目前未得到满足的医疗需求, we are exploring different mechanisms of action that address the biologically diverse br东 癌症 tumour environment at every stage of the disease continuum 和 across the various lines of treatment. Utilising our ever-growing underst和ing of the underlying br东 癌症 biology, we are dedicated to redefining treatment pathways 和 to help transform the lives of those living with br东 癌症.

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