Hada Manila, Oh Hannah, Fan Shaoqi, Falk Roni T, Geller Berta, Vacek Pamela, Weaver Donald, Shepherd John, Wang Jeff, Fan Bo, Herschorn Sally, Brinton Louise A, Xu Xia, Sherman Mark E, Trabert Britton, Gierach Gretchen L
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Division of Health Policy and Management, College of Health Science, Korea University, Seoul 02841, Korea.
J Clin Med. 2020 Jan 17;9(1):245. doi: 10.3390/jcm9010245.
The association of progesterone/progesterone metabolites with elevated mammographic breast density (MBD) and delayed age-related terminal duct lobular unit (TDLU) involution, strong breast cancer risk factors, has received limited attention. Using a reliable liquid chromatography-tandem mass-spectrometry assay, we quantified serum progesterone/progesterone metabolites and explored cross-sectional relationships with MBD and TDLU involution among women, ages 40-65, undergoing diagnostic breast biopsy. Quantitative MBD measures were estimated in pre-biopsy digital mammograms. TDLU involution was quantified in diagnostic biopsies. Adjusted partial correlations and trends across MBD/TDLU categories were calculated. Pregnenolone was positively associated with percent MBD-area (MBD-A, rho: 0.30; p-trend = 0.01) among premenopausal luteal phase women. Progesterone tended to be positively associated with percent MBD-A among luteal phase (rho: 0.26; p-trend = 0.07) and postmenopausal (rho: 0.17; p-trend = 0.04) women. Consistent with experimental data, implicating an elevated 5α-pregnanes/3α-dihydroprogesterone (5αP/3αHP) metabolite ratio in breast cancer, higher 5αP/3αHP was associated with elevated percent MBD-A among luteal phase (rho: 0.29; p-trend = 0.08), but not postmenopausal women. This exploratory analysis provided some evidence that endogenous progesterone and progesterone metabolites might be correlated with MBD, a strong breast cancer risk factor, in both pre- and postmenopausal women undergoing breast biopsy. Additional studies are needed to understand the role of progesterone/progesterone metabolites in breast tissue composition and breast cancer risk.
孕酮/孕酮代谢物与乳腺钼靶密度升高（MBD）以及与年龄相关的终末导管小叶单位（TDLU） involution延迟（这两个都是强烈的乳腺癌风险因素）之间的关联受到的关注有限。我们使用可靠的液相色谱-串联质谱分析法，对40-65岁接受诊断性乳腺活检的女性血清中的孕酮/孕酮代谢物进行了定量，并探讨了其与MBD和TDLU involution的横断面关系。在活检前的数字乳腺钼靶片中估计定量MBD测量值。在诊断性活检中对TDLU involution进行定量。计算了MBD/TDLU类别之间的调整偏相关和趋势。在绝经前黄体期女性中，孕烯醇酮与MBD面积百分比（MBD-A，rho：0.30；p趋势=0.01）呈正相关。在黄体期（rho：0.26；p趋势=0.07）和绝经后（rho：0.17；p趋势=0.04）女性中，孕酮倾向于与MBD-A百分比呈正相关。与实验数据一致，提示乳腺癌中5α-孕烷/3α-二氢孕酮（5αP/3αHP）代谢物比值升高，在黄体期女性中，较高的5αP/3αHP与MBD-A百分比升高相关（rho：0.29；p趋势=0.08），但在绝经后女性中并非如此。这项探索性分析提供了一些证据，表明内源性孕酮和孕酮代谢物可能与接受乳腺活检的绝经前和绝经后女性中作为强烈乳腺癌风险因素的MBD相关。需要进一步的研究来了解孕酮/孕酮代谢物在乳腺组织组成和乳腺癌风险中的作用。
