Insulin, Insulin-Like Growth Factor-I, and Risk of Breast Cancer in Postmenopausal Women

Gunter, Marc J.; Hoover, Donald R.; Yu, Herbert; Wassertheil‐Smoller, Sylvia; Rohan, Thomas E.; Manson, JoAnn E.; Li, Jixin; Ho, Gloria Y.F.; Xue, Xiaonan; Anderson, Garnet L.; Kaplan, Robert C.; Harris, Tiffany G.; Howard, Barbara V.; Wylie‐Rosett, Judith; Burk, Robert D.; Strickler, Howard D.

doi:10.1093/jnci/djn415

Cited by 491 publications

(425 citation statements)

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“…Table 2 The mean, median/interquartile range (IQR) , and hazard ratio for recurrence for insulin, IGF-binding protein-1 (IGFBP-1) Evidence from the European Prospective Investigation into Cancer and Nutrition (EPIC) suggested a positive association between IGF and breast cancer incidence only among postmenopausal women (Rinaldi et al 2006), while previous study findings suggested an association only among premenopausal women (Renehan et al 2004). More recently, a pooled analyses of 17 prospective studies found a positive association between IGF1 and breast cancer incidence regardless of menopausal status (Endogenous Hormones and Breast Cancer Collaborative Group 2010), while results from the Women's Health Initiative Cohort and the Japan Collaborative Cohort Study for Evaluation of Cancer Risk failed to find an association (Gunter et al 2009, Sakauchi et al 2009). The study by Goodwin et al (2002), one of the few prospective studies that investigated the association of IGF1 and insulin in relation to breast cancer recurrence, reported comparable results and found a non-significant HR for recurrence of breast cancer among women with the highest IGF1 quartile compared with the lowest quartile (1.55 (95% CI 0.93-2.59)).…”

Section: Discussionmentioning

confidence: 94%

“…Most studies on IGF1 and its binding proteins have investigated their associations with breast cancer incidence rather than recurrence (Kaaks et al 2002, Renehan et al 2004, Rinaldi et al 2006, Gunter et al 2009, Sakauchi et al 2009, Endogenous Hormones and Breast Cancer Collaborative Group 2010). Table 2 The mean, median/interquartile range (IQR) , and hazard ratio for recurrence for insulin, IGF-binding protein-1 (IGFBP-1) Evidence from the European Prospective Investigation into Cancer and Nutrition (EPIC) suggested a positive association between IGF and breast cancer incidence only among postmenopausal women (Rinaldi et al 2006), while previous study findings suggested an association only among premenopausal women (Renehan et al 2004).…”

Section: Discussionmentioning

confidence: 99%

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IGF-1 and risk of additional breast cancer in the WHEL study

Al-Delaimy¹,

Flatt²,

Laughlin³

et al. 2011

Endocrine Related Cancer

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IGF1, IGF-binding protein-3 (IGFBP-3), IGFBP-1, insulin, leptin, and adiponectin have been inconsistently associated with breast cancer incidence. We explore how these factors are related to breast cancer recurrence and how tamoxifen treatment is related to IGF1 levels among breast cancer survivors in the Women's Healthy Eating and Living (WHEL) study. A nested case-control design was used to match breast cancer cases (who had an additional breast cancer event) to controls. Baseline blood samples from 510 matched cases and controls were analyzed for IGF1 levels; a subset of 188 pairs were analyzed for five other hormones and binding proteins. Median follow-up was 7.3 years. Matching was on recruitment site, cancer stage, age at cancer diagnosis, dates of cancer diagnosis, and randomization. Cox proportional hazards regression models, stratified on case-control pair, were used to assess the associations. Insulin, IGFBP-1, IGFBP-3, leptin, and adiponectin did not significantly predict recurrence of breast cancer. IGF1 was positively, but not significantly, associated with recurrence (hazard ratio (HR): 1.33 (95% confidence interval (CI) 0.98-1.81)) in the unadjusted analyses. Adjusting for menopausal status and tamoxifen use attenuated the HR to 1.07 (95% CI 0.76-1.40). Analyses of case-control pairs with discordant tamoxifen use show opposing HR: IGF1 predicts higher risk of recurrence if cases did not receive tamoxifen treatment. In conclusion, no significant association was found between IGF1 levels, or other related factors, and risk of additional breast cancer among breast cancer survivors. Tamoxifen can confound analysis of IGF1 and recurrence. This supports re-evaluating significance of IGF1 to breast cancer recurrence.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

IGF-1 and risk of additional breast cancer in the WHEL study

Al-Delaimy¹,

Flatt²,

Laughlin³

et al. 2011

Endocrine Related Cancer

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“…Hyperinsulinemia adversely affects prognosis in cancer patients (3,(7)(8)(9)(10)(11) and is an independent risk factor for several types of neoplasms, thus explaining the obesity-cancer association (12). Insulin can promote tumorigenesis through a direct effect on epithelial tissues acting on the insulin/insulin-like growth factor family of receptors (13), or indirectly by affecting the levels of other modulators, such as insulin-like growth factors, sex hormones, and adipokines (14,15).…”

Section: Introductionmentioning

confidence: 99%

Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis

DeCensi

Puntoni

Goodwin

et al. 2010

Cancer Prevention Research

820

569

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Metformin, an insulin-lowering agent, has been associated with decreased cancer risk in epidemiologic studies in diabetic patients. We performed a comprehensive literature search and meta-analysis of epidemiologic studies to assess the effect of metformin on cancer incidence and mortality in diabetic patients, using Pubmed, ISI Web of Science, Embase, and the Cochrane library until May 2009, with no language or time restrictions. Independent reports with sufficient information to allow risk estimation of cancer risk/mortality and a measure of uncertainty were reviewed and cross-checked independently by three investigators. Eleven studies were selected for relevance in terms of intervention, population studied, independence, and reporting of cancer incidence or mortality data, reporting 4,042 cancer events and 529 cancer deaths. A 31% reduction in overall summary relative risk (0.69; 95% confidence interval, 0.61-0.79) was found in subjects taking metformin compared with other antidiabetic drugs. The inverse association was significant for pancreatic and hepatocellular cancer, and nonsignificant for colon, breast, and prostate cancer. A trend to a dose-response relationship was noted. Metformin is associated with a decreased risk of cancer incidence compared with other treatments among diabetic patients. Given the retrospective nature of most studies and the possibility that the control treatments increase risk, phase II trials are needed before large cancer prevention trials are launched. Cancer Prev Res; 3(11); 1451-61. ©2010 AACR.

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“…Consumption of diets of high GI is linked with high blood glucose and insulin levels (Dong and Qin, 2011). Both substances have been positively associated with breast cancer (Larsson et al, 2007;Tworoger et al, 2007;Gunter et al, 2009;Minatoya et al, 2013). There was evidence that plasma C-peptide is increased at high insulin concentrations, and the marker is directly linked with GL (Wu et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Association between Vegetable, Fruit and Carbohydrate Intake and Breast Cancer Risk in Relation to Physical Activity

Kruk¹

2014

Asian Pacific Journal of Cancer Prevention

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Insulin, Insulin-Like Growth Factor-I, and Risk of Breast Cancer in Postmenopausal Women

Abstract: These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity-breast cancer relationship.

Cited by 491 publications

References 49 publications

IGF-1 and risk of additional breast cancer in the WHEL study

IGF-1 and risk of additional breast cancer in the WHEL study

Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis

Association between Vegetable, Fruit and Carbohydrate Intake and Breast Cancer Risk in Relation to Physical Activity

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