The etiology of triple-negative breast cancers (TNBC) is poorly understood. As many TNBCs develop prior to the initiation of breast cancer screening or at younger ages when the sensitivity of mammography is comparatively low, understanding the etiology of TNBCs is critical for discovering novel prevention approaches for these tumors. Furthermore, the higher incidence rate of estrogen receptor–negative breast cancers, and specifically, of TNBCs, among young African American women (AAW) versus white women is a source of racial disparities in breast cancer mortality. Whereas immune responses to TNBCs have received considerable attention in relation to prognosis and treatment, the concept that dysregulated immune responses may predispose to the development of TNBCs has received limited attention. We present evidence that dysregulated immune responses are critical in the pathogenesis of TNBCs, based on the molecular biology of the cancers and the mechanisms proposed to mediate TNBC risk factors. Furthermore, proposed risk factors for TNBC, especially childbearing without breastfeeding, high parity, and obesity, are more prevalent among AAW than white women. Limited data suggest genetic differences in immune responses by race, which favor a stronger Thr type 2 (Th2) immune response among AAW than white women. Th2 responses contribute to wound-healing processes, which are implicated in the pathogenesis of TNBCs. Accordingly, we review data on the link between immune responses and TNBC risk and consider whether the prevalence of risk factors that result in dysregulated immunity is higher among AAW than white women.

中文翻译：

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免疫反应和三阴性乳腺癌的风险：对非裔美国女性高发病率的影响

三阴性乳腺癌 (TNBC) 的病因知之甚少。由于许多 TNBC 在开始乳腺癌筛查之前或在乳房 X 线照相术的敏感性相对较低时发生在较年轻的年龄，因此了解 TNBC 的病因对于发现针对这些肿瘤的新预防方法至关重要。此外，年轻的非裔美国女性 (AAW) 与白人女性相比，雌激素受体阴性乳腺癌的发病率更高，特别是 TNBCs 的发病率更高，这是导致乳腺癌死亡率存在种族差异的一个原因。尽管对 TNBC 的免疫反应在预后和治疗方面受到了相当大的关注，但免疫反应失调可能导致 TNBC 发展的概念受到的关注有限。基于癌症的分子生物学和介导 TNBC 危险因素的机制，我们提出了免疫反应失调在 TNBC 发病机制中至关重要的证据。此外，提出的 TNBC 危险因素，尤其是未母乳喂养的生育、高产次和肥胖，在 AAW 中比白人女性更为普遍。有限的数据表明种族免疫反应存在遗传差异，这有利于 AAW 中的 Thr 2 型 (Th2) 免疫反应比白人女性更强。Th2 反应有助于伤口愈合过程，这与 TNBC 的发病机制有关。因此，我们审查了有关免疫反应与 TNBC 风险之间联系的数据，并考虑导致免疫失调的风险因素在 AAW 中的流行率是否高于白人女性。