Adverse outcome pathways (AOPs) are formalized and structured linear concepts that connect one molecular initiating event (MIE) to an adverse outcome (AO) via different key events (KE) through key event relationships (KER). They are mainly used in eco-toxicology toxicology, and regulatory health issues. AOPs must respond to specific guidelines from the Organization for Economic Co-operation and Development (OECD) to weight the evidence between each KE.

Breast cancer is the deadliest cancer in women with a poor prognosis in case of metastatic breast cancer. The role of the environments in the formation of metastasis has been suggested. We hypothesized that activation of the AhR (MIE), a xenobiotic receptor, could lead to breast cancer related death (AO), through different KEs, constituting a new AOP.

An artificial intelligence tool (AOP-helpfinder), which screens the available literature, was used to collect all existing scientific abstracts to build a novel AOP, using a list of key words. Four hundred and seven abstracts were found containing at least a word from our MIE list and either one word from our AO or KE list. A manual curation retained 113 pertinent articles, which were also screened using PubTator. From these analyses, an AOP was created linking the activation of the AhR to breast cancer related death through decreased apoptosis, inflammation, endothelial cell migration, angiogenesis, and invasion. These KEs promote an increased tumor growth, angiogenesis and migration which leads to breast cancer metastasis and breast cancer related death.

The evidence of the proposed AOP was weighted using the tailored Bradford Hill criteria and the OECD guidelines. The confidence in our AOP was considered strong. An in vitro validation must be carried out, but our review proposes a strong relationship between AhR activation and breast cancer-related death with an innovative use of an artificial intelligence literature search.

不良结果通路 (AOP) 是形式化和结构化的线性概念，通过关键事件关系 (KER) 将一个分子起始事件 (MIE)通过不同的关键事件 (KE) 连接到不良结果 (AO)。它们主要用于生态毒理学毒理学和监管健康问题。AOP 必须响应经济合作与发展组织 (OECD) 的具体指导方针，以权衡每个 KE 之间的证据。

在转移性乳腺癌的情况下，乳腺癌是预后不良的女性中最致命的癌症。已经提出环境在转移形成中的作用。我们假设，AhR (MIE) 是一种外源性受体，可通过不同的 KE 导致乳腺癌相关死亡 (AO)，从而构成新的 AOP。

筛选可用文献的人工智能工具（AOP-helpfinder）用于收集所有现有的科学摘要，以使用关键词列表构建新的 AOP。发现 407 个摘要至少包含我们的 MIE 列表中的一个词和我们的 AO 或 KE 列表中的一个词。手动策展保留了 113 篇相关文章，这些文章也使用 PubTator 进行了筛选。从这些分析中，创建了一个 AOP，通过减少细胞凋亡、炎症、内皮细胞迁移、血管生成和侵袭，将 AhR 的激活与乳腺癌相关死亡联系起来。这些 KE 促进肿瘤生长、血管生成和迁移，从而导致乳腺癌转移和乳腺癌相关死亡。

提议的 AOP 的证据使用量身定制的 Bradford Hill 标准和经合组织指南进行加权。对我们的 AOP 的信心被认为是强大的。必须进行体外验证，但我们的综述提出，通过人工智能文献搜索的创新使用，AhR 激活与乳腺癌相关死亡之间存在密切关系。