Insulin resistance and the development of breast cancer in premenopausal women: the Kangbuk Samsung Health Study

Abstract Objectives Breast cancer is the most diagnosed form of cancer among American women. Worldwide, it is second only to lung cancer. Phytosterols are phytochemicals found in plant foods that have potential benefits for breast cancer. Research on phytosterols and cancer associations to date has been limited to breast cancer cell lines and animal studies, and the results have been promising. Our objective is to examine the association between breast cancer incidence and phytosterol intake in the Adventist Health Study-2, a large cohort in North America. Methods The present study estimated the association between phytosterol intake and breast cancer incidence in 52,734 females who were part of the Adventist Health Study 2 (AHS-2) cohort. Breast cancer cases (n = 1050) were ascertained with tumor registries from 2008 to 2014. Phytosterols content in foods was quantified by using USDA 17 and other published sources. These values were used to estimate phytosterol intake from food intake assessed by a self-administered food frequency questionnaires (FFQ). Results Hazard ratios were below the null, but statistically non-significant for β-sitosterol [HR = 0.77, 95%CI (0.44–1.36)], campesterol [HR = 0.84, 95%CI (0.46–1.55)], stigmasterol [HR = 0.76 (0.46–1.26)], and total phytosterol [HR = 0.77, 95%CI (0.43–1.40)]. In premenopausal women, HRs ranged between 0.95–1.72; in postmenopausal women, HRs were below the null, ranging between 0.67–0.83. In both premenopausal and postmenopausal women, HRs were statistically non-significant. Conclusions The inverse association between phytosterol consumption and breast cancer incidence appears uncertain. The uncertainty possibly could be due to lack of power or measurement error. Additional epidemiological studies with a larger number of breast cancer cases, improved phytosterol intake estimates, or both are needed. Funding Sources Unilever Research &Development, Vlaardingen, The Netherlands.

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Use of Aspirin, Other Nonsteroidal Anti-inflammatory Drugs, and Acetaminophen and Risk of Breast Cancer Among Premenopausal Women in the Nurses' Health Study II

Archives of Internal Medicine ◽

10.1001/archinternmed.2008.537 ◽

2009 ◽

Vol 169 (2) ◽

pp. 115 ◽

Cited By ~ 32

Author(s):

A. Heather Eliassen ◽

Wendy Y. Chen ◽

Donna Spiegelman ◽

Walter C. Willett ◽

David J. Hunter ◽

...

Keyword(s):

Breast Cancer ◽

Premenopausal Women ◽

Health Study ◽

Inflammatory Drugs ◽

Anti Inflammatory

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Insulin-like growth factor-I, its binding proteins (IGFBP-1 and IGFBP-3), and growth hormone and breast cancer risk in The Nurses Health Study II

Endocrine Related Cancer ◽

10.1677/erc.1.01149 ◽

2006 ◽

Vol 13 (2) ◽

pp. 583-592 ◽

Cited By ~ 99

Author(s):

Eva S Schernhammer ◽

Jeff M Holly ◽

David J Hunter ◽

Michael N Pollak ◽

Susan E Hankinson

Keyword(s):

Breast Cancer ◽

Growth Hormone ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Premenopausal Women ◽

Health Study ◽

Blood Collection ◽

Factor I ◽

Igf I ◽

Igfbp 3

Earlier data suggest that the relationship between circulating insulin-like growth factor I (IGF-I) levels and breast cancer risk differs according to menopausal status. We evaluated the association between IGF levels as well as the primary regulator of IGF-I production, growth hormone (GH), and breast cancer risk in the Nurses’ Health Study II (NHS II) cohort, a large cohort of primarily premenopausal women. We conducted a case-control study nested within the prospective NHS II cohort. Plasma concentrations of IGF-I, IGF binding protein (IGFBP)-3, IGFBP-1, and GH were measured in blood samples collected between 1996 and 1999. Totally 317 women were identified who had a diagnosis of invasive or in situ breast cancer between the date of blood collection and June 1 2003; 75% of these women were premenopausal at blood collection. To each of the 317 women, two controls were age-matched for a total of 634 controls. We used conditional logistic regression models to estimate the relative risk of breast cancer. Overall, plasma IGF-I, IGFBP-1, IGFBP-3, and GH levels were not associated with breast cancer risk (relative risks, top vs bottom quartile; IGF-I, 0.98, 95% confidence interval (CI), 0.69–1.39; IGFBP-1, 0.95, 95% CI, 0.63–1.41; IGFBP-3, 1.10, 95% CI, 0.78–1.54; GH, 1.09, 95% CI, 0.82–1.46). These risks were similar for premenopausal women of age 45 years or less. Further adjustment for additional breast cancer risk factors did not change these estimates. In conclusion, circulating IGF-I, IGFBP-1, IGFBP-3, and GH levels appear to have no important association with breast cancer risk in a large cohort of premenopausal women.

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Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study

10.1101/2021.10.08.21264729 ◽

2021 ◽

Author(s):

Julia Debik ◽

Hartmut Schaefer ◽

Trygve Andreassen ◽

Feng Wang ◽

Fang Fang ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Premenopausal Women ◽

Health Study ◽

Breast Cancer Patients ◽

Serum Samples ◽

Lipoprotein Subfractions ◽

Premenopausal Breast Cancer

Background: The aim of this study was to investigate if serum lipoprotein and metabolic profiles of healthy women can predict the risk of developing breast cancer in the future, and to gain a better understanding of the etiology of the disease. Methods: From a cohort of 70 000 participants within the Trondelag Health Study (HUNT study), we identified 1199 women who developed breast cancer within a 22 year follow-up period. Through a nested case-control study design, future breast cancer patients and matching controls (n = 2398) were analysed. Using nuclear magnetic resonance (NMR) spectroscopy, 28 metabolites and 112 lipoprotein subfractions were quantified from prediagnostic serum samples. Logistic regression was used to test metabolites and lipoprotein subfractions for associations with breast cancer risk and partial least-squares discriminant analysis (PLS-DA) models were built to predict future disease. Results: Among premenopausal women (554 cases) 14 lipoprotein subfractions were associated with long-term breast cancer risk. In specific, different subfractions of VLDL particles (in particular VLDL-2, VLDL-3 and VLDL-4) were inversely associated with breast cancer. For total VLDL: apolipoprotein B, cholesterol, free cholesterol and phospholipids were inversely associated with premenopausal breast cancer risk, and in addition total and HDL-4 triglycerides. No significant association was found in postmenopausal women. Conclusions: We identified several associations between lipoprotein subfractions and long-term risk of breast cancer in premenopausal women. Inverse associations between several VLDL subfractions and breast cancer risk were found, revealing an altered metabolism in the endogenous lipid pathway many years prior to a breast cancer diagnosis.

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Circulating amino acids and amino acid-related metabolites and risk of breast cancer among predominantly premenopausal women

npj Breast Cancer ◽

10.1038/s41523-021-00262-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Oana A. Zeleznik ◽

Raji Balasubramanian ◽

Yibai Zhao ◽

Lisa Frueh ◽

Sarah Jeanfavre ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Amino Acids ◽

Amino Acid ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Kynurenic Acid ◽

Conditional Logistic Regression ◽

Premenopausal Women ◽

Health Study

AbstractKnown modifiable risk factors account for a small fraction of premenopausal breast cancers. We investigated associations between pre-diagnostic circulating amino acid and amino acid-related metabolites (N = 207) and risk of breast cancer among predominantly premenopausal women of the Nurses’ Health Study II using conditional logistic regression (1057 cases, 1057 controls) and multivariable analyses evaluating all metabolites jointly. Eleven metabolites were associated with breast cancer risk (q-value < 0.2). Seven metabolites remained associated after adjustment for established risk factors (p-value < 0.05) and were selected by at least one multivariable modeling approach: higher levels of 2-aminohippuric acid, kynurenic acid, piperine (all three with q-value < 0.2), DMGV and phenylacetylglutamine were associated with lower breast cancer risk (e.g., piperine: ORadjusted (95%CI) = 0.84 (0.77–0.92)) while higher levels of creatine and C40:7 phosphatidylethanolamine (PE) plasmalogen were associated with increased breast cancer risk (e.g., C40:7 PE plasmalogen: ORadjusted (95%CI) = 1.11 (1.01–1.22)). Five amino acids and amino acid-related metabolites (2-aminohippuric acid, DMGV, kynurenic acid, phenylacetylglutamine, and piperine) were inversely associated, while one amino acid and a phospholipid (creatine and C40:7 PE plasmalogen) were positively associated with breast cancer risk among predominately premenopausal women, independent of established breast cancer risk factors.

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