Dataset Information

Hormone therapy, estrogen metabolism, and risk of breast cancer in the Women's Health Initiative Hormone Therapy Trial.

ABSTRACT: In the Women's Health Initiative Hormone Trials (WHI-HT), breast cancer risk was increased with estrogen plus progestin (E+P) but not with unopposed estrogen (E-alone). We hypothesized that E+P would preferentially metabolize to 16?-hydroxyestrone (16?-OHE1) rather than 2-hydroxyestrone (2-OHE1), and that breast cancer risk would be associated with baseline and 1 year changes in estrogen metabolites: positively for 16?-OHE1 levels and negatively for levels of 2-OHE-1 and the 2:16 ratio.In a prospective case-control study nested in the WHI-HT, 845 confirmed breast cancer cases were matched to 1,690 controls by age and ethnicity. Using stored serum, 2-OHE1 and 16?-OHE1 levels were measured by enzyme immunoassay at baseline, and for those randomized to active treatment (n = 1,259), at 1 year.The 1-year increase in 16?-OHE1 was greater with E+P than E-alone (median 55.5 pg/mL vs. 43.5 pg/mL, P < 0.001), but both increased 2-OHE1 by ?300 pg/mL. Breast cancer risk was modestly associated with higher baseline levels of 2-OHE1 and the 2:16 ratio, and for estrogen receptor+/progesterone+ cases only, higher baseline 16?-OHE1 levels. For those randomized to active treatment, breast cancer risk was associated with greater increase in 2-OHE-1 and the 2:16 ratio, but associations were not significant.Although E+P modestly increased 16?-OHE1 more than E-alone, increase in 16?-OHE1 was not associated with breast cancer.Study results do not explain differences between the WHI E+P and WHI E-alone breast cancer results but metabolism of oral HT, which may explain smaller than expected increase in breast cancer compared with endogenous estrogens.

SUBMITTER: Mackey RH

PROVIDER: S-EPMC3493689 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hormone therapy, estrogen metabolism, and risk of breast cancer in the Women's Health Initiative Hormone Therapy Trial.

Mackey Rachel H RH Fanelli Theresa J TJ Modugno Francesmary F Cauley Jane A JA McTigue Kathleen M KM Brooks Maria Mori MM Chlebowski Rowan T RT Manson JoAnn E JE Klug Thomas L TL Kip Kevin E KE Curb J David JD Kuller Lewis H LH

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20120829 11

<h4>Background</h4>In the Women's Health Initiative Hormone Trials (WHI-HT), breast cancer risk was increased with estrogen plus progestin (E+P) but not with unopposed estrogen (E-alone). We hypothesized that E+P would preferentially metabolize to 16α-hydroxyestrone (16α-OHE1) rather than 2-hydroxyestrone (2-OHE1), and that breast cancer risk would be associated with baseline and 1 year changes in estrogen metabolites: positively for 16α-OHE1 levels and negatively for levels of 2-OHE-1 and the 2 ...[more]

PMID: 22933427

Similar Datasets

Project description:Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women's Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ?2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk.

Project description:ObjectiveThe aim of this study was to assess vasomotor and other menopausal symptoms before starting estrogens or placebo, 1 year later, again at trial closure, and after stopping estrogens or placebo. The role of baseline symptoms and age was examined, as was the frequency and determinants of hormone use and symptom management strategies after discontinuing conjugated equine estrogens (CEE) or placebo.MethodsIntent-to-treat analyses of 10,739 postmenopausal women before and 1 year after randomization to CEE or placebo at 40 clinical centers and a cohort analysis of participants (n = 3,496) who continued taking assigned study pills up to trial closure and completed symptom surveys shortly before (mean, 7.4 +/- 1.1 y from baseline) and after (mean, 306 +/- 55 d after trial closure) stopping pills were performed. Generalized linear regression modeled vasomotor symptoms, vaginal dryness, breast tenderness, pain/stiffness, and mood swings as a function of treatment assignment and baseline symptoms, before and after stopping study pills.ResultsApproximately one third of participants reported at least one moderate to severe symptom at baseline. Fewer symptoms were reported with increasing age, except joint pain/stiffness, which was similar among age groups. At 1 year, hot flashes, night sweats, and vaginal dryness were reduced by CEE, whereas breast tenderness was increased. Breast tenderness was also significantly higher in the CEE group at trial closure. After stopping, vasomotor symptoms were reported by significantly more women who had reported symptoms at baseline, compared with those who had not, and by significantly more participants assigned to CEE (9.8%) versus placebo (3.2%); however, among women with no moderate or severe symptoms at baseline, more than five times as many reported hot flashes after stopping CEE (7.2%) versus placebo (1.5%).ConclusionsCEE significantly reduced vasomotor symptoms and vaginal dryness in women with baseline symptoms but increased breast tenderness. The likelihood of experiencing symptoms was significantly higher after stopping CEE than placebo regardless of baseline symptom status. These potential effects should be considered before initiating CEE to relieve menopausal symptoms.

Project description:To analyze the treatment effect of calcium+vitamin D supplementation, hormone therapy, both, and neither on cardiovascular disease risk factors.We conducted a prospective, randomized, double-blind, placebo-controlled trial among Women's Health Initiative (WHI) participants. The predefined primary outcome was low-density lipoprotein cholesterol (LDL-C).Between September 1993 and October 1998, a total of 68,132 women aged 50-79 years were recruited and randomized to the WHI-Dietary Modification (n=48,835) and WHI-Hormone Therapy trials (n=27,347). Subsequently, 36,282 women from WHI-Hormone Therapy (16,089) and WHI-Dietary Modification (n=25,210) trials were randomized in the WHI-Calcium+Vitamin D trial to 1,000 mg elemental calcium carbonate plus 400 international units vitamin D3 daily or placebo. Our study group included 1,521 women who participated in both the hormone therapy and calcium+vitamin D trials and were in the 6% subsample of trial participants with blood sample collections at baseline and years 1, 3, and 6. The average treatment effect with 95% confidence interval, for LDL-C, compared with placebo, was -1.6, (95% confidence interval [CI] -5.5 to 2.2) mg/dL for calcium+vitamin D alone, -9.0 (95% CI -13.0 to -5.1) mg/dL for hormone therapy alone, and -13.8 (95% CI -17.8 to -9.8) mg/dL for the combination. There was no evidence of a synergistic effect of calcium+vitamin D+hormone therapy on LDL-C (P value for interaction=.26) except in those with low total intakes of vitamin D, for whom there was a significant synergistic effect on LDL (P value for interaction=.03).Reductions in LDL-C were greater among women randomized to both calcium+vitamin D and hormone therapy than for those randomized to either intervention alone or to placebo. The treatment effect observed in the calcium+vitamin D+hormone therapy combination group may be additive rather than synergistic. For clinicians and patients deciding to begin calcium+vitamin D supplementation, current use of hormone therapy should not influence that decision.ClinicalTrials.gov, https://clinicaltrials.gov, NCT00000611.

Dataset Information

Hormone therapy, estrogen metabolism, and risk of breast cancer in the Women's Health Initiative Hormone Therapy Trial.

Publications

Hormone therapy, estrogen metabolism, and risk of breast cancer in the Women's Health Initiative Hormone Therapy Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets