Department of Pharmacology and Experimental Therapeutics, The University of Toledo, Toledo, Ohio, USA.
Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, Alabama, USA.
Cancer Rep (Hoboken). 2023 Sep;6 Suppl 1(Suppl 1):e1779. doi: 10.1002/cnr2.1779. Epub 2023 Jan 12.
In 2020, newly diagnosed breast cancer (BC) cases surpassed that of lung cancer among women, making it the most common female cancer globally. In spite of recent increases in incidence rates, mortality due to BC has declined since 1989. These declines have been attributed to advancements in treatment modalities as well as increased mammography surveillance. Despite these advances, African American (AA) women are 40% more likely to die from BC than Caucasian women. Multifactorial etiology has been implicated in the disparity of BC mortality rates among AA women. As an example, AA women have a disproportionate incidence of triple negative breast cancer (TNBC), which has a poor prognosis and marginal treatment options. Increasingly, the tumor microenvironment (TME) has gained relevance as it relates to primary tumor progression, metastasis and treatment possibilities. The treatment outcomes or pathological complete response (pCR) in TNBC among AA women are affected by differences in TME. The TME of AA women exhibit several variances in acellular and cellular components associated with pro-tumorigenic effects. For example, increased levels of the adipocyte-related hormone, resistin, the pro-inflammatory cytokine, IL-6, and the CC chemokine, CCL2, within the TME of AA women gives rise to an increased density of M2 macrophages, also known as tumor-associated macrophages. Elevated levels of vascular endothelial growth factor in the TME of AA women increase the vascular density or vascularity, which facilitate aggressive tumor growth and metastasis. Furthermore, a pro-tumorigenic TME is supported by increased levels of the CXC chemokine, CXCL12 that results in the recruitment of regulatory T lymphocytes (T ). Due to these and other differences in the TME of AA women, precision oncology can target specific aspects of the TME that may contribute to a poorer prognosis. In addition to the discrepancies in the TME, AA women face socio-economic barriers that limit their ability to access state-of-the-art, novel therapies against metastatic TNBC. In this review, we will provide a brief overview of the tumor immune microenvironment, immune-based treatment options for TNBC and their potential to decrease health disparities due to ethnicity.
2020 年,新诊断的乳腺癌(BC)病例超过了肺癌,成为全球最常见的女性癌症。尽管发病率最近有所上升,但自 1989 年以来,BC 的死亡率有所下降。这些下降归因于治疗方式的进步和增加的乳房 X 光筛查。尽管取得了这些进展,但非裔美国(AA)女性死于 BC 的可能性比白人女性高 40%。多因素病因与 AA 女性中 BC 死亡率的差异有关。例如,AA 女性中三阴性乳腺癌(TNBC)的发病率不成比例,这种癌症预后较差,治疗选择有限。越来越多的证据表明,肿瘤微环境(TME)与原发性肿瘤进展、转移和治疗可能性有关。AA 女性中 TNBC 的治疗结果或病理完全缓解(pCR)受到 TME 差异的影响。AA 女性的 TME 在与促肿瘤发生作用相关的无细胞和细胞成分方面存在几种差异。例如,TME 中脂肪细胞相关激素抵抗素、促炎细胞因子 IL-6 和 CC 趋化因子 CCL2 的水平升高,导致 M2 巨噬细胞(也称为肿瘤相关巨噬细胞)的密度增加。TME 中血管内皮生长因子水平升高会增加血管密度或血管生成,从而促进侵袭性肿瘤生长和转移。此外,TME 中高水平的 CXC 趋化因子 CXCL12 支持促肿瘤生成的 TME,导致调节性 T 淋巴细胞(Treg)的募集。由于 AA 女性的 TME 中存在这些和其他差异,精准肿瘤学可以针对可能导致预后较差的 TME 的特定方面进行靶向治疗。除了 TME 中的差异外,AA 女性还面临社会经济障碍,限制了她们获得针对转移性 TNBC 的最先进新型疗法的能力。在这篇综述中,我们将简要概述肿瘤免疫微环境、TNBC 的免疫治疗选择及其降低因种族而导致的健康差异的潜力。