BACKGROUND Mammographic breast density (MBD) is a strong risk factor and an intermediate phenotype for breast cancer, yet there are limited studies on how environmental pollutants are associated with MBD. OBJECTIVE We investigated associations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) levels with measures of MBD and evaluated if early life factors modified any associations. METHODS Metabolon performed metabolomics analysis using ultrahigh-performance liquid chromatography/tandem accurate mass spectrometry in fasting blood from 705 premenopausal women completing their annual screening mammogram in St. Louis, Missouri. We calculated least square means (LSM) of mammographic volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV) by quartiles (Q) of PFOS, PFOA, and PFHxS from multivariable linear regression modeling overall and stratified by recruitment period, race, age at menarche, and body shape at age 10. Models were adjusted for age, age at menarche, body fat percentage, race, family history of breast cancer, oral contraceptive use, alcohol consumption, parity/age at first birth, and body shape at age 10. RESULTS PFOS, PFOA, and PFHxS were not significantly associated with VPD or NDV. PFHxS was significantly positively associated with DV (Q1=67.64 cm3, Q2=69.91 cm3, Q3=69.06 cm3, Q4=75.79 cm3; p-trend=0.03). PFOS was positively associated with DV (Q1=65.45 cm3, Q2=70.74 cm3, Q3=73.31 cm3, Q4=73.52 cm3; p-trend=0.06) with DV being 8.1%, 12%, and 12.3% higher in Q2, Q3, and Q4 compared to Q1. Among women who were underweight/normal weight at age 10, PFOS was positively associated with VPD (Q1=9.02%, Q2=9.11%, Q3=9.48%, Q4=9.92%; p-trend=0.04) while there was an inverse association among women who were overweight/obese at age 10 (Q1=7.46%, Q2=6.94%, Q3=6.78%, Q4=5.47%; p-trend=0.005) (p-interaction=0.04). DISCUSSION We report novel associations of PFHxS and PFOS with DV in premenopausal women. PFOS, PFOA, and PFHxS were not associated with VPD and NDV. In addition, body shape at age 10 may modify the associations of PFOS with MBD. Further studies are needed to validate our findings and to evaluate the associations of other per- and polyfluoroalkyl substances (PFAS), as well as mixtures of PFAS, with MBD. https://doi.org/10.1289/EHP14065.

中文翻译：

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绝经前女性的 PFAS 水平、早期生活因素和乳房 X 光检查乳房密度。


背景乳房X线照相乳腺密度(MBD)是乳腺癌的一个强危险因素和中间表型，但关于环境污染物如何与MBD相关的研究有限。目的 我们调查了全氟辛烷磺酸 (PFOS)、全氟辛酸 (PFOA) 和全氟己烷磺酸 (PFHxS) 水平与 MBD 测量值之间的关联，并评估了早期生活因素是否改变了任何关联。方法 Metabolon 使用超高效液相色谱/串联精确质谱法对密苏里州圣路易斯完成年度乳房 X 光检查的 705 名绝经前妇女的空腹血液进行代谢组学分析。我们根据多变量线性回归模型，通过 PFOS、PFOA 和 PFHxS 的四分位数 (Q) 计算乳腺 X 线摄影体积百分比密度 (VPD)、致密体积 (DV) 和非致密体积 (NDV) 的最小二乘均值 (LSM)，并按招募期、种族、初潮年龄和 10 岁时的体型。模型根据年龄、初潮年龄、体脂百分比、种族、乳腺癌家族史、口服避孕药使用情况、饮酒量、胎次/首次年龄进行调整出生和 10 岁时的体型。结果 PFOS、PFOA 和 PFHxS 与 VPD 或 NDV 没有显着相关性。 PFHxS 与 DV 呈显着正相关（Q1=67.64 cm3、Q2=69.91 cm3、Q3=69.06 cm3、Q4=75.79 cm3；p 趋势=0.03）。 PFOS 与 DV 呈正相关（Q1=65.45 cm3、Q2=70.74 cm3、Q3=73.31 cm3、Q4=73.52 cm3；p 趋势=0.06），其中第 2 季度、第 3 季度的 DV 分别高出 8.1%、12% 和 12.3% ，以及 Q4 与 Q1 的比较。在 10 岁时体重不足/正常的女性中，PFOS 与 VPD 呈正相关（Q1=9.02%，Q2=9.11%，Q3=9.48%，Q4=9.92%；p 趋势=0。04）而 10 岁时超重/肥胖的女性之间存在负相关（Q1=7.46%，Q2=6.94%，Q3=6.78%，Q4=5.47%；p-趋势=0.005）（p-交互= 0.04）。讨论 我们报告了 PFHxS 和 PFOS 与绝经前妇女 DV 之间的新关联。 PFOS、PFOA 和 PFHxS 与 VPD 和 NDV 无关。此外，10 岁时的体型可能会改变 PFOS 与 MBD 的关联。需要进一步的研究来验证我们的研究结果，并评估其他全氟烷基物质和多氟烷基物质 (PFAS) 以及 PFAS 混合物与 MBD 的关联。 https://doi.org/10.1289/EHP14065。