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Oxidative Stress and Breast Cancer Risk in Premenopausal Women.

ABSTRACT: BACKGROUND:Detrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause. METHODS:We conducted a nested case-control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35-54 were eligible for selection. We matched controls 2:1 to cases on age and enrollment year and were breast cancer-free at the time of the corresponding case's diagnosis. Oxidative stress was measured by urinary F2-isoprostane and metabolite (15-F2t-isoprostane-M) concentrations. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with multivariable conditional logistic regression. RESULTS:After multivariable adjustment for body mass index (BMI) and other potential confounders, the OR for breast cancer comparing the >90th (?2.94?ng/mgCr) to <25th percentile (1.01?ng/mgCr) was 1.1 (CI: 0.65, 1.7) for F2-isoprostane and 0.70 (CI: 0.43, 1.1) for the metabolite. Higher metabolite concentrations were associated with lower breast cancer risk among women who were also premenopausal (353 cases, OR: 0.59, CI: 0.34, 1.0) or <46 years (82 cases, OR: 0.15, CI: 0.06, 0.42) at diagnosis. ORs for the metabolite and breast cancer were inverse among women with BMI 18.5-24.9?kg/m (OR: 0.47, CI: 0.18, 1.2, 208 cases) and >30?kg/m (OR: 0.71, CI: 0.30, 1.7, 107 cases), but not among women with BMI 25-29.9?kg/m (OR: 0.98, CI: 0.39, 2.5, 138 cases). CONCLUSIONS:Together with other studies, our results support a possible inverse association between oxidative stress and premenopausal breast cancer risk.

SUBMITTER: Nichols HB

PROVIDER: S-EPMC5580344 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Oxidative Stress and Breast Cancer Risk in Premenopausal Women.

Nichols Hazel B HB Anderson Chelsea C White Alexandra J AJ Milne Ginger L GL Sandler Dale P DP

Epidemiology (Cambridge, Mass.) 20170901 5

<h4>Background</h4>Detrimental effects of oxidative stress are widely recognized, but induction of apoptosis and senescence may also have benefits for cancer prevention. Recent studies suggest oxidative stress may be associated with lower breast cancer risk before menopause.<h4>Methods</h4>We conducted a nested case-control study (N = 457 cases, 910 controls) within the NIEHS Sister Study cohort of 50,884 women. Premenopausal women ages 35-54 were eligible for selection. We matched controls 2:1 ...[more]

PMID: 28520645

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Project description:BackgroundAs a special reproductive hormone and ovarian reserve indicator, the role of anti-Müllerian hormone (AMH) in premenopausal women with breast cancer deserves further study.MethodsWe conducted an in-depth analysis of the data from the EGOFACT study (NCT02518191), a phase Ⅲ, randomized, controlled trial involving premenopausal female breast cancer patients in two parallel groups: chemotherapy with or without gonadotropin-releasing hormone analogs (GnRHa). Three hundred thirty premenopausal women aged 25-49 years with operable stage I to III breast cancer were included in this study. The characteristics of ovarian reserve changes marked by AMH in the EGOFACT study and the factors affecting ovarian function in premenopausal women with breast cancer were analyzed.ResultsThe AMH level of the chemotherapy alone group decreased gradually within one year, while the AMH level of the GnRHa group was significantly higher as early as 6 months after chemotherapy and recovered to close to the baseline level 12 months after chemotherapy (F = 34.991, P < 0.001). Correlation analysis showed that the factors affecting AMH levels mainly included age, menarche age, body mass index (BMI), reproductive history, baseline follicle stimulating hormone (FSH) level, pathological stage and GnRHa application, but they had different effects on the incidence of premature ovarian insufficiency (POI) at different periods. Multivariate logistic regression analysis showed that menarche age younger than 14 years (OR 0.470 [0.259, 0.852], P = 0.013), baseline AMH level higher than 0.5 ng/mL (OR 9.590 [3.366, 27.320], P < 0.001), pathological stage Ⅰ(OR 0.315 [0.124, 0.798], P = 0.015) and GnRHa application (OR 0.090 [0.045, 0.183], P < 0.001) were independent factors conducive to protection of ovarian reserve, as well as to recovery of ovarian reserve.ConclusionsAge, menarche age, baseline AMH level, and GnRHa application are the most important influencing factors for ovarian reserve in premenopausal women with breast cancer.Trial registrationClinicalTrials.gov, NCT02518191, registered on Aug 5, 2015.

Project description:Endogenous estrogens and estrogen metabolism are hypothesized to be associated with premenopausal breast cancer risk but evidence is limited. We examined 15 urinary estrogens/estrogen metabolites and breast cancer risk among premenopausal women in a case-control study nested within the Nurses' Health Study II (NHSII). From 1996 to 1999, urine was collected from 18,521 women during the mid-luteal menstrual phase. Breast cancer cases (N = 247) diagnosed between collection and June 2005 were matched to two controls each (N = 485). Urinary estrogen metabolites were measured by liquid chromatography-tandem mass spectrometry and adjusted for creatinine level. Relative risks (RR) and 95% confidence intervals (CI) were estimated by multivariate conditional logistic regression. Higher urinary estrone and estradiol levels were strongly significantly associated with lower risk (top vs. bottom quartile RR: estrone = 0.52; 95% CI, 0.30-0.88; estradiol = 0.51; 95% CI, 0.30-0.86). Generally inverse, although nonsignificant, patterns also were observed with 2- and 4-hydroxylation pathway estrogen metabolites. Inverse associations generally were not observed with 16-pathway estrogen metabolites and a significant positive association was observed with 17-epiestriol (top vs. bottom quartile RR = 1.74; 95% CI, 1.08-2.81; P(trend) = 0.01). In addition, there was a significant increased risk with higher 16-pathway/parent estrogen metabolite ratio (comparable RR = 1.61; 95% CI, 0.99-2.62; P(trend) = 0.04). Other pathway ratios were not significantly associated with risk except parent estrogen metabolites/non-parent estrogen metabolites (comparable RR = 0.58; 95% CI, 0.35-0.96; P(trend) = 0.03). These data suggest that most mid-luteal urinary estrogen metabolite concentrations are not positively associated with breast cancer risk among premenopausal women. The inverse associations with parent estrogen metabolites and the parent estrogen metabolite/non-parent estrogen metabolite ratio suggest that women with higher urinary excretion of parent estrogens are at lower risk.

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Oxidative Stress and Breast Cancer Risk in Premenopausal Women.

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Oxidative Stress and Breast Cancer Risk in Premenopausal Women.

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