Per-和聚氟烷基物质(PFAS)是高度持久的内分泌干扰物质，可能导致乳腺癌的发生发展，但流行病学证据有限。我们在前瞻性情况下对Prostate、Lung、Colorectal和Ovarian Cancer Screening Trial中621例病例和621个匹配对照进行了嵌套病例-对照研究，研究了术前血清中全氟辛烷磺酸盐(PFOS)和全氟辛酸盐(PFOA)水平与绝经后乳腺癌风险的关系，总体和按激素受体状态分析。PFOS和PFOA的水平是基于使用超高效液相色谱串联质谱技术进行的血清代谢组学分析确定的。我们采用多元条件 logistic 回归模型来估计每个PFAS与总体乳腺癌风险、雌激素受体(ER)或孕激素受体(PR)状态、联合ER/PR状态之间的关系的奥斯比和95%置信区间( CI)。我们发现PFOS或PFOA与总体乳腺癌风险之间的关联证据很少。然而，在亚型特异性分析中，我们观察到PFOS的血清第三四分位数显著增加 ER +，PR + 和 ER +/PR + 肿瘤的风险(奥斯比[95% CI]= 1.59 [1.01-2.50]，2.34 [1.29-4.23] 和2.19 [1.21-3.98]，分别) ，以及升高但不统计学显著的ORs的第四四分位数。相反，对于PFOA，一般在上四分位数中与ER-，PR-，ER+/PR-和ER-/PR- 肿瘤存在适度的阳性关联。我们的研究结果支持血清PFOS与激素受体阳性肿瘤之间存在积极关联，以及PFOS和受体阴性肿瘤之间也可能存在阳性关联。未来的前瞻性研究需要结合肿瘤激素受体状态，更好地理解PFAS在乳腺癌发病机制中的作用。此文章受版权保护。版权所有，盗版必究。

Per- and polyfluoroalkyl substances (PFAS) are highly persistent endocrine-disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case-control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultra-performance liquid chromatography-tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype-specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs. lowest quartile of serum PFOS (ORs [95% CIs]=1.59 [1.01-2.50], 2.34 [1.29-4.23], and 2.19 [1.21-3.98], respectively) and elevated but non-statistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER-, PR-, ER+/PR-, and ER-/PR- tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor-positive tumors, and possibly between PFOA and receptor-negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.