Francies Flavia Zita, Hull Rodney, Khanyile Richard, Dlamini Zodwa
SA-MRC/UP Precision Prevention & Novel Drug Targets for HIV-Associated Cancers (PPNDTHAC) Extramural Unit, Pan African Cancer Research Institute (PACRI), University of Pretoria, Faculty of Health Sciences Hatfield, 0028, South Africa.
Am J Cancer Res. 2020 May 1;10(5):1568-1591. eCollection 2020.
Breast cancer is a common malignancy among women worldwide. Regardless of the economic status of a country, breast cancer poses a burden in prevention, diagnosis and treatment. Developed countries such as the U.S. have high incidence and mortality rates of breast cancer. Although low incidence rates are observed in developing countries, the mortality rate is on the rise implying that low- to middle-income countries lack the resources for preventative screening for early detection and adequate treatment resources. The differences in incidence between countries can be attributed to changes in exposure to environmental risk factors, behaviour and lifestyle factors of the different population groups. Genomic modifications are an important factor that significantly alters the risk profile of breast tumourigenesis. The incidence of early-onset breast cancer is increasing and evidence shows that early onset of breast cancer is far more aggressive than late onset of the disease; possibly due to the difference in genetic alterations or tumour biology. Alternative splicing is a pivotal factor in the progressions of breast cancer. It plays a significant role in tumour prognosis, survival and drug resistance; hence, it offers a valuable option as a therapeutic target. In this review, the differences in breast cancer incidence and mortality rates in developed countries will be compared to low- to middle-income countries. The review will also discuss environmental and lifestyle risk factors, and the underlying molecular mechanisms, genetic variations or mutations and alternative splicing that may contribute to the development and novel drug targets for breast cancer.
乳腺癌是全球女性中常见的恶性肿瘤。无论一个国家的经济状况如何，乳腺癌在预防、诊断和治疗方面都构成负担。美国等发达国家乳腺癌的发病率和死亡率很高。虽然发展中国家的发病率较低，但死亡率正在上升，这意味着低收入和中等收入国家缺乏用于早期检测的预防性筛查资源和足够的治疗资源。各国发病率的差异可归因于不同人群接触环境风险因素、行为和生活方式因素的变化。基因组修饰是显著改变乳腺肿瘤发生风险特征的一个重要因素。早发性乳腺癌的发病率正在上升，而且有证据表明，早发性乳腺癌比晚发性乳腺癌更具侵袭性；这可能是由于基因改变或肿瘤生物学的差异。可变剪接是乳腺癌进展中的一个关键因素。它在肿瘤预后、生存和耐药性方面发挥着重要作用；因此，它作为一种治疗靶点提供了一个有价值的选择。在这篇综述中，将比较发达国家与低收入和中等收入国家乳腺癌发病率和死亡率的差异。该综述还将讨论环境和生活方式风险因素，以及可能导致乳腺癌发展的潜在分子机制、基因变异或突变和可变剪接，以及乳腺癌的新型药物靶点。
