Wang Tengteng, Nichols Hazel B, Nyante Sarah J, Bradshaw Patrick T, Moorman Patricia G, Kabat Geoffrey C, Parada Humberto, Khankari Nikhil K, Teitelbaum Susan L, Terry Mary Beth, Santella Regina M, Neugut Alfred I, Gammon Marilie D
Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
JNCI Cancer Spectr. 2020 Mar 2;4(3):pkaa014. doi: 10.1093/jncics/pkaa014. eCollection 2020 Jun.
Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE) and 16-hydroxyestrone (16-OHE) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer.
This population-based study was initiated in 1996-1997 with spot urine samples obtained shortly after diagnosis (mean = 96 days) from 683 women newly diagnosed with first primary breast cancer and 434 age-matched women without breast cancer. We measured urinary concentrations of 2-OHE and 16-OHE using an enzyme-linked immunoassay. Vital status was determined via the National Death Index (n = 244 deaths after a median of 17.7 years of follow-up). We used multivariable-adjusted Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided.
Urinary concentrations of the 2-OHE to 16-OHE ratio (>median of 1.8 vs ≤median) were inversely associated with all-cause mortality (HR = 0.74, 95% CI = 0.56 to 0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR = 0.73, 95% CI = 0.45 to 1.17) and cardiovascular diseases mortality (HR = 0.76, 95% CI = 0.47 to 1.23), although the 95% confidence intervals included the null. Similar findings were also observed for women without breast cancer. The association with all-cause mortality was more pronounced among breast cancer participants who began chemotherapy before urine collection (n = 118, HR = 0.42, 95% CI = 0.22 to 0.81) than among those who had not (n = 559, HR = 0.98, 95% CI = 0.72 to 1.34; = .008).
The urinary 2-OHE to 16-OHE ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection.
2-羟雌酮（2-OHE）和16-羟雌酮（16-OHE）的雌激素代谢物浓度可能与乳腺癌发生有关。然而，尚无研究调查它们对乳腺癌患者死亡率的可能影响。
这项基于人群的研究始于1996 - 1997年，收集了683例新诊断为原发性乳腺癌的女性患者在诊断后不久（平均96天）的即时尿样，以及434例年龄匹配的无乳腺癌女性的尿样。我们使用酶联免疫分析法测量尿中2-OHE和16-OHE的浓度。通过国家死亡指数确定生存状态（在中位随访17.7年后有244例死亡）。我们使用多变量调整的Cox比例风险模型来估计雌激素代谢物与死亡率之间关联的风险比（HRs）和95%置信区间（CIs）。我们使用似然比检验评估效应修饰。所有统计检验均为双侧检验。
在乳腺癌女性患者中，尿中2-OHE与16-OHE的比值（>中位数1.8 vs ≤中位数）与全因死亡率呈负相关（HR = 0.74，95% CI = 0.56至0.98）。乳腺癌死亡率（HR = 0.73，95% CI = 0.45至1.17）和心血管疾病死亡率（HR = 0.76，95% CI = 0.47至1.23）也观察到风险降低，尽管95%置信区间包含无效值。在无乳腺癌的女性中也观察到类似结果。在收集尿液前开始化疗的乳腺癌参与者（n = 118，HR = 0.42，95% CI = 0.22至0.81）中，与全因死亡率的关联比未开始化疗的参与者（n = 559，HR = 0.98，95% CI = 0.72至1.34；P = 0.008）更明显。
尿中2-OHE与16-OHE的比值可能与长期全因死亡率呈负相关，这可能取决于收集尿液时的癌症治疗状态。
