Obesity, weight change, fasting insulin, proinsulin, C-peptide, and insulin-like growth factor-1 levels in women with and without breast cancer: the Rancho Bernardo Study.

Postmenopausal overweight women have an increased risk of breast cancer. The link between obesity and breast cancer could be mediated through hyperinsulinemia. Insulin and insulin-like growth factor-1 (IGF-1) stimulate mammary cell proliferation in vitro, and cell proliferation is directly linked to the risk of breast cancer. Our objective was to investigate the relationship between breast cancer and body composition, IGF-1, proinsulin, C-peptide, and fasting insulin. A case-control study was conducted of 438 community-dwelling women aged 53-90 years in 1992-1994 who had no history of cancer at the baseline visit in 1972-1974. Women were excluded who were using estrogen replacement therapy (ERT) or tamoxifen at the 1992-1994 visit, when IGF-1, proinsulin, fasting insulin, and C-peptide levels were measured. Prior ERT, alcohol and tobacco use, exercise, and reproductive history were recorded. Weight, height, and waist/hip ratio were measured. The 45 women with breast cancer had similar baseline body mass indices to the 393 women without breast cancer but had gained significantly more weight between the baseline visit in 1972-1974 and 1992-1994, (age-adjusted relative risk [RR] 1.05/kg, 95% confidence interval [CI] 1.01-1.09, p = 0.016). Proinsulin, fasting insulin, and C-peptide were each significantly positively correlated with both current weight and weight gain. However, levels of these hormones and IGF-1 did not differ significantly between women with and without breast cancer (all 95% CI within 0.996-1.004). Past ERT was significantly more common among women with breast cancer (p = 0.015), and duration of use was significantly longer (age-adjusted RR 1.13 per year of use, 95% CI 1.08-1.18, p = 0.000). The risk of breast cancer was significantly increased in women who had gained weight or used ERT. This increased risk was not associated with circulating levels of IGF-1, fasting insulin, proinsulin, or C-peptide.

[1]  Ivar Heuch,et al.  Population attributable risk for breast cancer: diet, nutrition, and physical exercise. , 2000 .

[2]  M. Espeland,et al.  Effect of Postmenopausal Hormone Therapy on Glucose and Insulin Concentrations , 1998, Diabetes Care.

[3]  K. Overvad,et al.  A woman's build and the risk of breast cancer. , 1998, European journal of cancer.

[4]  E. Riboli,et al.  Breast‐cancer incidence in relation to height, weight and body‐fat distribution in the Dutch “DOM” cohort , 1998, International journal of cancer.

[5]  O. Olopade,et al.  Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes. , 1998, Journal of the National Cancer Institute.

[6]  David J Hunter,et al.  Circulating concentrations of insulin-like growth factor I and risk of breast cancer , 1998, The Lancet.

[7]  Julian Peto,et al.  Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer , 1997, The Lancet.

[8]  J. Palmgren,et al.  Body‐size indicators and risk of breast cancer according to menopause and estrogen‐receptor status , 1996, International journal of cancer.

[9]  H. Pijl,et al.  Bodyweight Change as an Adverse Effect of Drug Treatment , 1996, Drug safety.

[10]  G A Colditz,et al.  Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. , 1995, Journal of the National Cancer Institute.

[11]  R. Kazer.  Insulin resistance, insulin‐like growth factor I and breast cancer: A hypothesis , 1995, International journal of cancer.

[12]  T. C. Linders,et al.  Insulin‐like growth‐factor‐binding protein 3 is decreased in early‐stage operable pre‐menopausal breast cancer , 1995, International journal of cancer.

[13]  C. Cirrincione,et al.  Is Body Fat Topography a Risk Factor for Breast Cancer? , 1993, Annals of Internal Medicine.

[14]  J L Kelsey,et al.  Reproductive factors and breast cancer. , 1993, Epidemiologic reviews.

[15]  L. Bernstein,et al.  Endogenous hormones and breast cancer risk. , 1993, Epidemiologic reviews.

[16]  W. Willett,et al.  Diet, body size, and breast cancer. , 1993, Epidemiologic reviews.

[17]  A. A. Hart,et al.  Insulin resistance and breast‐cancer risk , 1992, International journal of cancer.

[18]  S. Shapiro,et al.  Breast cancer and cigarette smoking: a hypothesis. , 1991, American journal of epidemiology.

[19]  K. Ho,et al.  Contrasting effects of oral and transdermal routes of estrogen replacement therapy on 24-hour growth hormone (GH) secretion, insulin-like growth factor I, and GH-binding protein in postmenopausal women. , 1991, The Journal of clinical endocrinology and metabolism.

[20]  R. Vigneri,et al.  Progestins increase insulin receptor content and insulin stimulation of growth in human breast carcinoma cells. , 1990, Cancer research.

[21]  B. Jacobsen,et al.  Level of education, use of oral contraceptives and reproductive factors: the Tromsø Study. , 1990, International journal of epidemiology.

[22]  M. Pike,et al.  Increased cell division as a cause of human cancer. , 1990, Cancer research.

[23]  M. Pike,et al.  The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. , 1988, European journal of cancer & clinical oncology.

[24]  F. Alexander,et al.  The menopause and breast cancer. , 1987, Journal of epidemiology and community health.

[25]  W. Daughaday,et al.  Inhibition of access of bound somatomedin to membrane receptor and immunobinding sites: a comparison of radioreceptor and radioimmunoassay of somatomedin in native and acid-ethanol-extracted serum. , 1980, The Journal of clinical endocrinology and metabolism.

[26]  E. Barrett-Connor.  The prevalence of diabetes mellitus in an adult community as determined by history or fasting hyperglycemia. , 1980, American journal of epidemiology.

[27]  A. Lazarow,et al.  Immunoassay of Insulin: Two Antibody System: Plasma Insulin Levels of Normal, Subdiabetic and Diabetic Rats , 1963, Diabetes.