Urinary estrogen metabolites and long-term mortality following breast cancer
Menée à partir d'échantillons urinaires prélevés sur 683 patientes atteintes d'un cancer du sein primitif récemment diagnostiqué et sur 434 témoins, cette étude évalue l'association entre les concentrations de deux métabolites des œstrogènes (2-hydroxy-estrone et 16-hydroxy-estrone) et le risque de décès à long terme
Background : Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE1) and 16-hydroxyestrone (16-OHE1) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer.
Methods : 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-OHE1 and 16-OHE1 using an enzyme linked immuno-assay. 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 (95%CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided.
Results : Urinary concentrations of the 2-OHE1/16-OHE1 ratio (>median of 1.8 vs. ≤median) were inversely associated with all-cause mortality (HR = 0.74, 95%CI=0.56-0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR = 0.73, 95%CI=0.45-1.17) and cardiovascular diseases mortality (HR = 0.76, 95%CI=0.47-1.23), although the 95%CIs 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=0.22-0.81) than among those who had not (N = 559, HR = 0.98, 95%CI=0.72-1.34, pinteraction=0.008.
Conclusions : The urinary 2-OHE1/16-OHE1 ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection.
JNCI Cancer Spectrum , article en libre accès, 2019