Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer

Lønning, Per Eystein; Helle, Svein Inge; Johannessen, Dag Clement; Ekse, Dagfinn; Adlercreutz, Herman

doi:10.1007/bf01806162

Cited by 48 publications

(33 citation statements)

References 23 publications

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“…The reasons for this increased mortality are likely to be multifaceted including factors related to socioeconomic status, access to health care, course of treatment, or characteristics of the tumor such as tumor size, grade, or stage [41,[43][44][45][46]. Given that circulating estrogen levels are associated both with breast cancer onset [47,48] and prognosis [2], the results of the present study are consistent with a potential role of IRS-1 in racial/ethnic differences in breast cancer prognosis. However, there is no apparent association of the G972R variant with stage of disease in this data and the women have not been observed long enough to examine survival.…”

Section: Discussionsupporting

confidence: 80%

“…Cumulative estrogen exposure after the diagnosis of breast cancer may also influence breast cancer prognosis. High plasma estrogen levels have been associated with a shortened disease-free interval in postmenopausal breast cancer patients with recurrent disease [2]. Tamoxifen, an antiestrogen in the breast, blocks estrogen binding to the estrogen receptor (ER) and is now a standard part of clinical breast cancer care.…”

Section: Introductionmentioning

confidence: 99%

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An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors

Fan

McKean‐Cowdin

Bernstein

et al. 2006

Breast Cancer Res Treat

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Insulin receptor substrate-1 (IRS-1) is a key downstream signaling molecule common to both the insulin and IGF signaling pathways that can interact with the estrogen pathway to regulate breast cell growth. We investigated whether a putative functional variant for IRS-1 (G972R) influences circulating levels of sex hormones, sex hormone binding globulin (SHBG), C-peptide, and insulinlike growth factor 1 (IGF-1) levels among postmenopausal African-American and non-Hispanic white breast cancer patients enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. Circulating levels of sex hormones and growth factors can influence breast cancer recurrence and survival. Serum estrone, estradiol, testosterone, SHBG, IGF-1 and C-peptide were measured in 468 patients at 30+ months post diagnosis. Non-protein bound hormone levels (free estradiol, free testosterone) were calculated. In African-American patients, the IRS-1 variant was associated with increased serum levels of estrone (p=0.02), free estradiol (p=0.04), total testosterone (p=0.04), free testosterone (p=0.006) and decreased levels of sex hormone-binding globulin (p=0.02). No association was present for white patients. Our findings provide suggestive evidence that IRS-1 G972R variant may be associated with circulating levels of sex hormones and SHBG in African American breast cancer survivors.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors

Fan

McKean‐Cowdin

Bernstein

et al. 2006

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…Exercise interventions have been shown to decrease circulating estrogen levels in premenopausal and postmenopausal women (5,6). High endogenous estrogen levels have been shown to be positively associated with breast cancer recurrence in postmenopausal women (7) and are linked to an increased risk for primary breast cancer (8,9).…”

Section: Introductionmentioning

confidence: 99%

Role of Physical Activity in Modulating Breast Cancer Risk as Defined byAPCandRASSF1APromoter Hypermethylation in Nonmalignant Breast Tissue

Coyle

Xie²,

Lewis

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Physical activity reduces breast cancer risk. Promoter hypermethylation of the tumor suppressor genes APC and RASSF1A, which is potentially reversible, is associated with breast cancer risk. We conducted a cross-sectional study in 45 women without breast cancer to determine the association of physical activity with promoter hypermethylation of APC and RASSF1A in breast tissue. We used quantitative methylation-specific PCR to test the methylation status of APC and RASSF1A, and questionnaires to assess study covariates and physical activity (measured in metabolic equivalent hours per week). In univariate analyses, the study covariate, benign breast biopsy number, was positively associated with promoter hypermethylation of APC (P = 0.01) but not RASSF1A. Mulitvariate logistic regression indicated that, although not significant, physical activities for a lifetime [odds ratio (OR), 0.57; 95% confidence interval (95% CI), 0.22-1.45; P = 0.24], previous 5 years (OR, 0.62; 95% CI, 0.34-1.12; P = 0.11), and previous year (OR, 0.72; 95% CI, 0.43-1.22; P = 0.22) were inversely related to promoter hypermethylation of APC but not RASSF1A for all physical activity measures. Univariate logistic regression indicated that physical activities for a lifetime, previous 5 years, and previous year were inversely associated with benign breast biopsy number, and these results were approaching significance for lifetime physical activity (OR, 0.41; 95% CI, 0.16-1.01; P = 0.05) and significant for physical activity in the previous 5 years (OR, 0.57; 95% CI, 0.34-0.94; P = 0.03). The study provides indirect evidence supporting the hypothesis that physical activity is inversely associated with promoter hypermethylation of tumor suppressor genes, such as APC, in nonmalignant breast tissue. (Cancer Epidemiol Biomarkers Prev 2007;16(2):192 -6)

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“…Lønning et al (31) demonstrated that circulating estrogen levels were significantly associated with poorer DFS in postmenopausal patients. In a case-control cohort study, Rock et al (32) indicated that total estradiol, bioavailable estradiol and free estradiol circulating concentrations were associated with the risk of recurrence.…”

Section: Discussionmentioning

confidence: 99%

Rs1008805 polymorphism of CYP19A1 gene is associated with the efficacy of hormone therapy in stage I‑II and operable stage III breast cancer

et al. 2017

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Abstract. It has been hypothesized that single nucleotide polymorphisms in CYP19A1 gene may alter aromatase activity and circulating steroid hormone levels in females. Therefore, it is biologically reasonable that CYP19A1 rs1008805 (A/G) polymorphism may be associated with the clinical outcome of hormone therapy. Genotyping for the CYP19A1 rs1008805 polymorphism was performed for 287 females with hormone receptor (HR)-positive early breast cancer, and potential associations were evaluated between CYP19A1 rs1008805 genotypes and disease-free survival (DFS). Based on the analysis of the whole cohort, no significant differences were observed between rs1008805 genotypes and DFS. However, in postmenopausal females, rs1008805 variants were significantly associated with DFS (AA vs. AG vs. GG, 89.2 vs. 58.2 vs. 32.7 months; P=0.019). In addition, when the population was divided into two cohorts, females with the GG variant exhibited a significantly poorer DFS [GG vs. AA or AG, 32.7 vs. 70.6 months; hazard ratio (HR), 3.613; 95% confidence interval (CI), 1.380-9.457; P=0.005]. Furthermore, when adjusted for other patient features in multivariate analyses, GG genotype remained an independent prognostic marker for DFS (HR, 3.439; 95% CI, 1.251-9.456; P=0.017). However, there were no significant differences in DFS between patients harboring the minor allele and those with the homozygous common allele (AG or GG vs. AA, 52.4 vs. 89.2 months; HR, 1.288; 95% CI, 0.705-2.353; P=0.408). There were also no associations between rs1008805 polymorphism and DFS for premenopausal females. In conclusion, the homozygous minor allele (GG) of CYP19A1 rs1008805 was identified to be significantly associated with an inferior clinical outcome of hormone therapy in postmenopausal hormone receptor-positive patients with early breast cancer. If confirmed by further study, genotyping for CYP19A1 rs1008805 polymorphism may provide predictive information to improve the selection of endocrine treatment. IntroductionOver the last three decades, the number of breast cancer cases has increased worldwide (1) to become the most likely cause of cancer mortality and morbidity in females (2). Increased levels of aromatase expression have been observed in breast lesions compared with normal breast tissue (3,4) and alterations in aromatase expression are associated with the pathogenesis of breast cancer (5,6).Approximately two thirds of breast cancer cases overexpress estrogen receptors (ER) and/or progesterone receptors (PgR) (7,8). Consequently, endocrine therapy, including tamoxifen or aromatase inhibitors (AIs), has become an effective treatment for these patients. For decades, 5-year tamoxifen administration was the gold standard for the adjuvant endocrine treatment of breast cancer (9). More recently, postmenopausal patients have also had the option of receiving AIs as an alternative to tamoxifen, or following tamoxifen treatment (10). The presence and intensity of ER and/or PgR are useful predictive markers for the response to hormone therapy in clinica...

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Influence of plasma estrogen levels on the length of the disease-free interval in postmenopausal women with breast cancer

Cited by 48 publications

References 23 publications

An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors

An association between a common variant (G972R) in the IRS-1 gene and sex hormone levels in post-menopausal breast cancer survivors

Role of Physical Activity in Modulating Breast Cancer Risk as Defined byAPCandRASSF1APromoter Hypermethylation in Nonmalignant Breast Tissue

Rs1008805 polymorphism of CYP19A1 gene is associated with the efficacy of hormone therapy in stage I‑II and operable stage III breast cancer

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