乳腺癌

building on our history 和 evolving with the science

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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. 纵观澳门第一赌城在线娱乐的历史, 澳门第一赌城在线娱乐的创新科学已经为乳腺癌患者带来了潜在的改变实践的药物, 尽管澳门第一赌城在线娱乐已经走了这么远, 还有很多工作要做. 澳门第一赌城在线娱乐致力于进一步研究，重新定义乳腺癌治疗模式.

Br东 癌症 remains the most common 癌症 in women around the world1 和 is the leading cause of 癌症 death in women.2 男性易患乳腺癌，尽管发病率远低于女性.3 It can begin in various parts of the organ, 包括管道, 小叶(产生牛奶), 或者是中间的组织.4

Br东 癌症 care has transformed over the last 50 years5, 和 we’re proud to have continuously supported this through research.

The introduction of mastectomy (a surgery to remove the entire br东6) 和 chemotherapy into clinical practice, as well as advancements in screening 和 diagnosis, 即乳房x光检查, 提高对疾病的认识大大提高了乳腺癌患者的存活率.4,7

随着分子生物学的进步, systems biology 和 genome sciences in recent years, we have exp和ed our underst和ing of br东 癌症 at the cellular, 分子和基因组水平.4 澳门第一赌城在线娱乐现在知道了 br东 癌症 is one of the most biologically diverse tumour types with various factors fuelling its development 和 progression.4

今天，澳门第一赌城在线娱乐可以对乳腺癌患者进行分类并帮助他们进行治疗 激素受体 or HER2表达状况，以及他们是否有 BRCA突变. 但随着澳门第一赌城在线娱乐对导致乳腺癌的不同因素的了解不断加深, 澳门第一赌城在线娱乐为新亚型患者开发潜在药物的能力也将如此.

今天澳门第一赌城在线娱乐如何对乳腺癌进行分类

To help determine the best management approach for br东 癌症, 确定可能驱动肿瘤生长的关键受体或蛋白质是至关重要的. 受体或蛋白质的表达反过来决定了乳腺癌的分类.

扩大信息图表

Br东 癌症 classification – 激素受体s

Hormones are the driving factor in the development of br东 tissue, 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, their role in tumour formation has been well documented for over a century.8 The growth 和 proliferation of female br东 tissue occurs during puberty when hormonal stimulation triggers cellular differentiation. 青春期的变化很大程度上受到类固醇激素和雌激素的影响8 和孕激素, 哪些是乳房正常功能发育的“主要调节器”.9

The two steroid hormones bind to cellular receptors 和 stimulate growth. 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. To be labelled as 激素受体 (HR)-positive, over 1% of br东 癌症 cells must express ER, 或两个.11 当这些受体少于1%时，癌症被标记为激素受体(HR)阴性11 (if any receptors at all) 和 it is unlikely the cause of tumour growth.12

The role of hormones in br东 癌症 has been well understood for some time, 因此，第一批专门为乳腺癌设计的药物是激素疗法.10 这些疗法可以防止癌细胞使用雌激素或黄体酮，并以多种方式起作用.

雌激素受体比孕激素受体在乳腺癌中更为普遍, 大约80%的乳腺癌是激素依赖性和雌激素受体阳性(ER+).13 雌激素受体阴性/孕激素受体阳性(ER-/PR+)的肿瘤病例极为罕见14 和, 因此, 治疗通常针对涉及雌激素的途径——这些通常被称为内分泌抑制剂.15

指导治疗意见的作用: 芳香酶抑制剂(AIs), 例如, 防止某些组织(卵巢除外)产生雌激素, 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, 内质网信号通路被破坏，癌细胞使用雌激素的能力被剥夺. SERDs are often used in metastatic disease17 - 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

在过去几十年中，可用于HR+乳腺癌的药物数量持续增长, 但仍有更多工作要做. 现在，澳门第一赌城在线娱乐正努力以澳门第一赌城在线娱乐丰富的传统为基础，进一步改变患有HR+疾病妇女的生活.

Br东 癌症 classification – HER2 receptors

在80年代早期, the human epidermal growth factor 2 (HER2) gene, which helps maintain a healthy cell lifecycle, 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

扩大信息图表

在指导治疗方案方面的作用: Although traditionally HER2+ br东 癌症 is associated with poor prognosis21, this has improved meaningfully as monoclonal anti-HER2 antibodies, tyrosine kinase inhibitors 和 antibody-drug conjugates (ADCs) have been developed to target the oncogenic driver.22

ADCs consist of two 癌症-fighting medicines in one, 细胞毒素, also known as chemotherapy or the “payload”, 和 a monoclonal antibody (that binds to a specific target expressed on 癌症 cells) joined together by a linker. This enables the highly targeted delivery of 细胞毒素, which is known for having poor specificity towards 癌症 cells, directly into the 癌症 cell t在这里by potentially sparing normal cells.23 要了解有关adc的更多信息，请单击 在这里. 

Br东 癌症 classification – Triple-Negative 乳腺癌 (TNBC)

Triple-negative br东 癌症s (TNBC) do not express oestrogen receptors, progesterone receptors 和 do not have high levels of HER2 overexpression, so they are considered ‘negative’ for all three. TNBC占所有乳腺癌的10-15%，在40岁以下的女性中更为常见. 众所周知，这种特殊形式的乳腺癌具有特别的侵袭性和快速生长, 有很高的转移风险, 不幸的是, is more likely to recur after treatment than other br东 癌症s.24,25

在指导治疗方案方面的作用: The number of treatment options available for TNBC is significantly less than that of other forms of br东 癌症 due to the lack of known actionable biomarker targets. 和大多数乳腺癌一样, 如果疾病还没有转移, surgery is usually employed with chemotherapy used to either shrink the tumour before surgery or reduce the chance of the 癌症 coming back following surgery. 在某些情况下, women with TNBC may also be eligible for immunotherapy w在这里 the body’s own immune system is harnessed to fight the 癌症.24

Br东 癌症 classification – BRCA突变s

基因组学的发展确定了进一步的生物标志物，可以针对乳腺癌采取行动, 具体地说, 这两个 BR东 CAncer susceptibility (BRCA) genes – 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), 具体地说 in homologous recombination repair (HRR), which is just one of the pathways to do so. 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, 它们不能发挥功能，患癌症的风险就会增加.28 平均, 携带BRCA1或BRCA2基因突变的女性在80岁之前患乳腺癌的几率高达70%.29

在指导治疗方案方面的作用: 在细胞水平上, mutated BRCA genes lead to dysfunctional HRR pathways 和 to survive, 细胞必须依靠其他途径. This is what can be exploited through targeted therapy. PARP抑制剂捕获PARP酶，阻止单链DNA断裂被修复. This leads to increases in double-str和ed DNA breaks, which cannot be repaired by the dysfunctional HRR pathway. 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

澳门在线赌城娱乐致力于研究DDR抑制乳腺癌的潜力. 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.

未来澳门第一赌城在线娱乐将如何改变乳腺癌的分类和治疗方式

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, AstraZeneca has contributed to advancements in br东 癌症 care, 拥有一系列开创性的药物, including targeted monotherapies 和 precision/personalised combinations, 哪些药物在改善乳腺癌患者的预后方面继续发挥着关键作用.

Br东 癌症 remains a focus for AstraZeneca. As our underst和ing of the features that fuel this complex tumour type grows, 澳门第一赌城在线娱乐对乳腺癌的分类和治疗方法无疑会改变, something we are spearheading at AstraZeneca. 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

To help address the ongoing unmet medical needs, 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. 利用澳门第一赌城在线娱乐对潜在乳腺癌生物学不断增长的理解, we are dedicated to redefining treatment pathways 和 to help transform the lives of those living with br东 癌症.

参考文献

  1. 西格尔R, 等. 2020年癌症统计数据. 临床医生癌症杂志. 70(1), pp.7-30.
  2. 世界卫生组织. 研究. Estimated number of deaths in 2018, worldwide, females, all ages. 可以在 http://gco.研究.fr /今天/ online-analysis-table?v=2018&模式=癌症&mode_population =大洲&人口= 900&数量= 900&关键= asr&性别= 2&癌症= 39&类型= 1&统计= 1&流行率= 0&population_group = 0&ages_group % 5 b % 5 d = 0&ages_group % 5 b % 5 d = 17&group_癌症 = 0&include_nmsc = 1&include_nmsc_other = 1 2022年5月访问.
  3. Gucalp, 等. Male br东 癌症: a disease distinct from female br东 癌症. 乳腺癌治疗. 2019;173(1):37-48.
  4. 冯Y, 等. Br东 癌症 development 和 progression: Risk factors, 癌症干细胞, 信号通路, 基因组学, 分子发病机制. 基因 & 疾病. 2018;5(2), 77–106.
  5. 英国癌症研究中心. 2019年英国癌症. 可以在 http://www.Cancerresearchuk.org/sites/default/files/state_of_the_nation_april_2019.pdf 2022年5月访问.
  6. 癌症.org. Mastectomy | Mastectomies For 乳腺癌. 可以在 http://www.Cancer.org/Cancer/breast-Cancer/treatment/surgery-for-breast-Cancer/mastectomy.html 2022年5月访问.
  7. 世界卫生组织. WHO position paper on mammography screening. 可以在 http://apps.who.int/iris/bitstream/handle/10665/137339/9789241507936_eng.pdf;jsessionid=6ABDEA86654F84E089CCEF024C8E2009?sequence=1 2022年5月访问.
  8. Trabert B, 等. 黄体酮和乳腺癌. Endocr牧师. 2020;41(2):320-344.
  9. 希尔顿H, 等. 正常乳腺中的雌激素和孕激素信号及其对癌症发展的影响. 分子与细胞内分泌学. 2018;466, pp.2-14.
  10. 癌症.网. Estrogen And Progesterone Receptor Testing For 乳腺癌. 可以在 http://www.Cancer.net/research-and-advocacy/asco-care-and-treatment-recommendations-patients/estrogen-and-progesterone-receptor-testing-breast-Cancer 2022年5月访问.
  11. Allison K, 等. Estrogen 和 Progesterone Receptor Testingin 乳腺癌. 美国临床肿瘤学会/美国病理学家学会指南更新. Arch Pathol Lab Med. 2020;144:545-563.
  12. 癌症.org. 乳腺癌 Hormone Receptor Status | Estrogen Receptor. 可以在 http://www.Cancer.org/Cancer/breast-Cancer/understanding-a-breast-Cancer-diagnosis/breast-Cancer-hormone-receptor-status.html. 2022年5月访问.
  13. 中央社报道. 乳腺癌的类型. 可以在 http://www.WebMD.com/breast-Cancer/breast-Cancer-types-er-positive-her2-positive#:~:text=About%2080%25%20of%20all%20breast,response%20to%20another%20hormone%2C%20progesterone. 2022年5月访问.
  14. 竞技场 等. ER−/PR+/HER2− br东 癌症 type shows the highest proliferative activity among all other combined phenotypes 和 is more common in young patients: Experience with 6643 br东 癌症 cases. 乳房杂志. 2019;25(3), pp.381-385.
  15. 癌症.org. 乳腺癌的激素治疗. 可以在 http://www.Cancer.org/Cancer/breast-Cancer/treatment/hormone-therapy-for-breast-Cancer.html 2022年5月访问.
  16. 王L, 等. 一类新的选择性雌激素受体降解物(SERDs):扩展PROTAC Degrons工具箱. ACS药物化学快报. 2018;9(8), pp.803-808.
  17. 帕特尔, 等. Selective estrogen receptor modulators (SERMs) 和 selective estrogen receptor degraders (SERDs) in 癌症 treatment. 药理学 & 治疗. 2018;186:1-24.
  18. 王妃, 等. 激素受体阳性乳腺癌的内分泌抵抗——从机制到治疗. 内分泌学前沿. 2019;10.
  19. Lu等人. Design 和 Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant 乳腺癌. 医学化学杂志. 2019;62, pp.11301-11323.
  20. 国家癌症研究所. HER2基因与乳腺癌有关 刺激新疗法的发展. 可以在 http://www.Cancer.gov /IARC/进步/发现/ her2 2022年5月访问.
  21. 王, 等. her2阳性乳腺癌的靶向治疗选择和未来展望. 信号转导和靶向治疗. 2019;4(34):1-22.
  22. Rinnerthaler G, 等. HER2 Directed Antibody-Drug-Conjugates beyond T-DM1 in 乳腺癌. International journal of molecular sciences. 2019;20(5):1115.
  23. 丹N, 等. 用于癌症治疗的抗体-药物结合物:化学到临床意义. 制药业(瑞士巴塞尔). 2018;11(2), 32.
  24. 癌症.org. Triple-Negative 乳腺癌 | Details, Diagnosis, And Signs. 可以在 http://www.Cancer.org/Cancer/breast-Cancer/understanding-a-breast-Cancer-diagnosis/types-of-breast-Cancer/triple-negative.html. 2022年5月访问.
  25. wak, 等. 乳腺癌治疗:综述. 《澳门第一赌城在线娱乐》. 2019 ;321(3), pp.288-300.
  26. 东海里, 等. BRCA1/2 testing: therapeutic implications for br东 癌症 Management. 英国癌症杂志. 2018;119:141-152.
  27. Bohen年代, 等. DNA Damage Response –An Emerging Target for Groundbreaking 癌症 Therapies. 欧洲肿瘤 & 血液学 2018; 14 (1): 2 - 7.
  28. 国家癌症研究所. BRCA Mutations: 癌症 Risk And Genetic Testing. 可以在 http://www.Cancer.gov/about-Cancer/causes-prevention/genetics/brca-fact-sheet. 2022年5月访问.
  29. 美国癌症协会. 乳腺癌 Risk Factors You Cannot Change. 可以在  http://www.Cancer.org/Cancer/breast-Cancer/risk-and-prevention/breast-Cancer-risk-factors-you-cannot-change.html 2022年5月访问.
  30. Bonadio R, 等. 卵巢癌同源重组缺乏症的流行病学及治疗进展. 诊所. 2018, 73 (1).