Journal of Clinical Oncology, Vol 20, Issue 1
(January), 2002: 42-51
© 2002 American Society for Clinical Oncology
Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study
By Pamela J. Goodwin,
Marguerite Ennis,
Kathleen I. Pritchard,
Maureen E. Trudeau,
Jarley Koo,
Yolanda Madarnas,
Warren Hartwick,
Barry Hoffman,
Nicky Hood
From the Department of Medicine, Department of Pathology and Laboratory Medicine, and Department of Surgery, Division of Clinical Epidemiology at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital; Toronto-Sunnybrook Regional Cancer Centre; Sunnybrook and Womens College Health Sciences Centre; St Michaels Hospital; and University of Toronto, Toronto, Ontario, Canada.
Address reprint requests Pamela J. Goodwin, MD, Mount Sinai Hospital, 600 University Ave, Ste 1284, Toronto, Ontario M5G 1X5, Canada; email: pgoodwin{at}mtsinai.on.ca
PURPOSE: Insulin, a member of a family of growth factors that includes insulin-like growth factor (IGF)-I and IGF-II, exerts mitogenic effects on normal and malignant breast epithelial cells, acting via insulin and IGF-I receptors. Because of this and because of its recognized association with obesity, an adverse prognostic factor in breast cancer, we examined the prognostic associations of insulin in early-stage breast cancer.
PATIENTS AND METHODS: A cohort of 512 women without known diabetes, who had early-stage (T1 to T3, N0 to N1, and M0) breast cancer, was assembled and observed prospectively. Information on traditional prognostic factors and body size was collected, and fasting blood was obtained.
RESULTS: Fasting insulin was associated with distant recurrence and death; the hazard ratios and 95% confidence intervals (CI) for those in the highest (> 51.9 pmol/L) versus the lowest (< 27.0 pmol/L) insulin quartile were 2.0 (95% CI, 1.2 to 3.3) and 3.1 (95% CI, 1.7 to 5.7), respectively. There was some evidence to suggest that the association of insulin with breast cancer outcomes may be nonlinear. Insulin was correlated with body mass index (Spearman r = 0.59, P < .001), which, in turn, was associated with distant recurrence and death (P < .001). In multivariate analyses that included fasting insulin and available tumor- and treatment-related variables, adjusted hazard ratios for the upper versus lower insulin quartile were 2.1 (95% CI, 1.2 to 3.6) and 3.3 (95% CI, 1.5 to 7.0) for distant recurrence and death, respectively.
CONCLUSION: Fasting insulin level is associated with outcome in women with early breast cancer. High levels of fasting insulin identify women with poor outcomes in whom more effective treatment strategies should be explored.
This article has been cited by other articles:

|
 |

|
 |
 
J. K. Litton, A. M. Gonzalez-Angulo, C. L. Warneke, A. U. Buzdar, S.-W. Kau, M. Bondy, S. Mahabir, G. N. Hortobagyi, and A. M. Brewster
Relationship Between Obesity and Pathologic Response to Neoadjuvant Chemotherapy Among Women With Operable Breast Cancer
J. Clin. Oncol.,
September 1, 2008;
26(25):
4072 - 4077.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C M Friedenreich and A E Cust
Physical activity and breast cancer risk: impact of timing, type and dose of activity and population subgroup effects
Br. J. Sports Med.,
August 1, 2008;
42(8):
636 - 647.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Goodwin
Host-Related Factors in Breast Cancer: An Underappreciated Piece of the Puzzle?
J. Clin. Oncol.,
July 10, 2008;
26(20):
3299 - 3300.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. C. Barnett, M. Shah, K. Redman, D. F. Easton, B. A.J. Ponder, and P. D. P. Pharoah
Risk Factors for the Incidence of Breast Cancer: Do They Affect Survival From the Disease?
J. Clin. Oncol.,
July 10, 2008;
26(20):
3310 - 3316.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Pasanisi, E. Venturelli, D. Morelli, L. Fontana, G. Secreto, and F. Berrino
Serum Insulin-Like Growth Factor-I and Platelet-Derived Growth Factor as Biomarkers of Breast Cancer Prognosis
Cancer Epidemiol. Biomarkers Prev.,
July 1, 2008;
17(7):
1719 - 1722.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Sachdev and D. Yee
Disrupting Insulin-Like Growth Factor Signaling as a Potential Cancer Therapy
Am. Assoc. Cancer Res. Educ. Book,
April 12, 2008;
2008(1):
39 - 58.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Goodwin
Insulin in the Adjuvant Breast Cancer Setting: A Novel Therapeutic Target for Lifestyle and Pharmacologic Interventions?
J. Clin. Oncol.,
February 20, 2008;
26(6):
833 - 834.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Ligibel, N. Campbell, A. Partridge, W. Y. Chen, T. Salinardi, H. Chen, K. Adloff, A. Keshaviah, and E. P. Winer
Impact of a Mixed Strength and Endurance Exercise Intervention on Insulin Levels in Breast Cancer Survivors
J. Clin. Oncol.,
February 20, 2008;
26(6):
907 - 912.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. N. Holick, P. A. Newcomb, A. Trentham-Dietz, L. Titus-Ernstoff, A. J. Bersch, M. J. Stampfer, J. A. Baron, K. M. Egan, and W. C. Willett
Physical Activity and Survival after Diagnosis of Invasive Breast Cancer
Cancer Epidemiol. Biomarkers Prev.,
February 1, 2008;
17(2):
379 - 386.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. P. Rose, S. M. Haffner, and J. Baillargeon
Adiposity, the Metabolic Syndrome, and Breast Cancer in African-American and White American Women
Endocr. Rev.,
December 1, 2007;
28(7):
763 - 777.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Min Park, M. Kyung Lim, K. Won Jung, S. Ae Shin, K.-Y. Yoo, Y. Ho Yun, and B. Yul Huh
Prediagnosis Smoking, Obesity, Insulin Resistance, and Second Primary Cancer Risk in Male Cancer Survivors: National Health Insurance Corporation Study
J. Clin. Oncol.,
October 20, 2007;
25(30):
4835 - 4843.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Xue and K. B Michels
Diabetes, metabolic syndrome, and breast cancer: a review of the current evidence
Am. J. Clinical Nutrition,
September 1, 2007;
86(3):
823S - 835S.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. L Blackburn and K. A Wang
Dietary fat reduction and breast cancer outcome: results from the Women's Intervention Nutrition Study (WINS)
Am. J. Clinical Nutrition,
September 1, 2007;
86(3):
878S - 881S.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. P. Pierce, M. L. Stefanick, S. W. Flatt, L. Natarajan, B. Sternfeld, L. Madlensky, W. K. Al-Delaimy, C. A. Thomson, S. Kealey, R. Hajek, et al.
Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity
J. Clin. Oncol.,
June 10, 2007;
25(17):
2345 - 2351.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Vona-Davis and D. P Rose
Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression
Endocr. Relat. Cancer,
June 1, 2007;
14(2):
189 - 206.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. M. Butturini, F. J. Dorey, B. J. Lange, D. W. Henry, P. S. Gaynon, C. Fu, J. Franklin, S. E. Siegel, N. L. Seibel, P. C. Rogers, et al.
Obesity and Outcome in Pediatric Acute Lymphoblastic Leukemia
J. Clin. Oncol.,
May 20, 2007;
25(15):
2063 - 2069.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Extermann and A. Hurria
Comprehensive Geriatric Assessment for Older Patients With Cancer
J. Clin. Oncol.,
May 10, 2007;
25(14):
1824 - 1831.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Sachdev and D. Yee
Disrupting insulin-like growth factor signaling as a potential cancer therapy
Mol. Cancer Ther.,
January 1, 2007;
6(1):
1 - 12.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. T. Chlebowski, G. L. Blackburn, C. A. Thomson, D. W. Nixon, A. Shapiro, M. K. Hoy, M. T. Goodman, A. E. Giuliano, N. Karanja, P. McAndrew, et al.
Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study
J Natl Cancer Inst,
December 20, 2006;
98(24):
1767 - 1776.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. M. Park, M. K. Lim, S. A. Shin, and Y. H. Yun
Impact of Prediagnosis Smoking, Alcohol, Obesity, and Insulin Resistance on Survival in Male Cancer Patients: National Health Insurance Corporation Study
J. Clin. Oncol.,
November 1, 2006;
24(31):
5017 - 5024.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Cowey and R. W. Hardy
The Metabolic Syndrome: A High-Risk State for Cancer?
Am. J. Pathol.,
November 1, 2006;
169(5):
1505 - 1522.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. T. Budd, M. Cristofanilli, M. J. Ellis, A. Stopeck, E. Borden, M. C. Miller, J. Matera, M. Repollet, G. V. Doyle, L. W.M.M. Terstappen, et al.
Circulating Tumor Cells versus Imaging--Predicting Overall Survival in Metastatic Breast Cancer.
Clin. Cancer Res.,
November 1, 2006;
12(21):
6403 - 6409.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Zakikhani, R. Dowling, I. G. Fantus, N. Sonenberg, and M. Pollak
Metformin Is an AMP Kinase-Dependent Growth Inhibitor for Breast Cancer Cells
Cancer Res.,
November 1, 2006;
66(21):
10269 - 10273.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Sanderson, J. R. Daling, D. R. Doody, and K. E. Malone
Perinatal factors and mortality from breast cancer.
Cancer Epidemiol. Biomarkers Prev.,
October 1, 2006;
15(10):
1984 - 1987.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Visovsky
Muscle strength, body composition, and physical activity in women receiving chemotherapy for breast cancer.
Integr Cancer Ther,
September 1, 2006;
5(3):
183 - 191.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. T. Bloomgarden
Third Annual World Congress on the Insulin Resistance Syndrome: Associated conditions.
Diabetes Care,
September 1, 2006;
29(9):
2165 - 2174.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A M Lorincz and S Sukumar
Molecular links between obesity and breast cancer.
Endocr. Relat. Cancer,
June 1, 2006;
13(2):
279 - 292.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. F. McCarty and K. I. Block
Toward a core nutraceutical program for cancer management.
Integr Cancer Ther,
June 1, 2006;
5(2):
150 - 171.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
G. A. Porter, K. M. Inglis, L. A. Wood, and P. J. Veugelers
Effect of Obesity on Presentation of Breast Cancer
Ann. Surg. Oncol.,
March 1, 2006;
13(3):
327 - 332.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M.-H. Tao, X.-O. Shu, Z. X. Ruan, Y.-T. Gao, and W. Zheng
Association of Overweight with Breast Cancer Survival
Am. J. Epidemiol.,
January 15, 2006;
163(2):
101 - 107.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. Irwin, A. McTiernan, L. Bernstein, F. D. Gilliland, R. Baumgartner, K. Baumgartner, and R. Ballard-Barbash
Relationship of Obesity and Physical Activity with C-Peptide, Leptin, and Insulin-Like Growth Factors in Breast Cancer Survivors
Cancer Epidemiol. Biomarkers Prev.,
December 1, 2005;
14(12):
2881 - 2888.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Diorio, M. Pollak, C. Byrne, B. Masse, N. Hebert-Croteau, M. Yaffe, G. Cote, S. Berube, and J. Brisson
Levels of C-Peptide and Mammographic Breast Density
Cancer Epidemiol. Biomarkers Prev.,
November 1, 2005;
14(11):
2661 - 2664.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. I. Zia, L. L. Siu, G. R. Pond, and E. X. Chen
Comparison of Outcomes of Phase II Studies and Subsequent Randomized Control Studies Using Identical Chemotherapeutic Regimens
J. Clin. Oncol.,
October 1, 2005;
23(28):
6982 - 6991.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Goodwin, M. Ennis, I. G. Fantus, K. I. Pritchard, M. E. Trudeau, J. Koo, and N. Hood
Is Leptin a Mediator of Adverse Prognostic Effects of Obesity in Breast Cancer?
J. Clin. Oncol.,
September 1, 2005;
23(25):
6037 - 6042.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Loi, R. L. Milne, M. L. Friedlander, M. R.E. McCredie, G. G. Giles, J. L. Hopper, and K.-A. Phillips
Obesity and Outcomes in Premenopausal and Postmenopausal Breast Cancer
Cancer Epidemiol. Biomarkers Prev.,
July 1, 2005;
14(7):
1686 - 1691.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Griggs, M. E. S. Sorbero, and G. H. Lyman
Undertreatment of Obese Women Receiving Breast Cancer Chemotherapy
Arch Intern Med,
June 13, 2005;
165(11):
1267 - 1273.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. D. Holmes, W. Y. Chen, D. Feskanich, C. H. Kroenke, and G. A. Colditz
Physical Activity and Survival After Breast Cancer Diagnosis
JAMA,
May 25, 2005;
293(20):
2479 - 2486.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. T. Chlebowski
Obesity and Early-Stage Breast Cancer
J. Clin. Oncol.,
March 1, 2005;
23(7):
1345 - 1347.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. L. Irwin, A. McTiernan, R. N. Baumgartner, K. B. Baumgartner, L. Bernstein, F. D. Gilliland, and R. Ballard-Barbash
Changes in Body Fat and Weight After a Breast Cancer Diagnosis: Influence of Demographic, Prognostic, and Lifestyle Factors
J. Clin. Oncol.,
February 1, 2005;
23(4):
774 - 782.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. T. Chlebowski, M. Pettinger, M. L. Stefanick, B. V. Howard, Y. Mossavar-Rahmani, and A. McTiernan
Insulin, Physical Activity, and Caloric Intake in Postmenopausal Women: Breast Cancer Implications
J. Clin. Oncol.,
November 15, 2004;
22(22):
4507 - 4513.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Goodwin, M. Ennis, L. J. Bordeleau, K. I. Pritchard, M. E. Trudeau, J. Koo, and N. Hood
Health-Related Quality of Life and Psychosocial Status in Breast Cancer Prognosis: Analysis of Multiple Variables
J. Clin. Oncol.,
October 15, 2004;
22(20):
4184 - 4192.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Borugian, S. B. Sheps, C. Kim-Sing, C. Van Patten, J. D. Potter, B. Dunn, R. P. Gallagher, and T. G. Hislop
Insulin, Macronutrient Intake, and Physical Activity: Are Potential Indicators of Insulin Resistance Associated with Mortality from Breast Cancer?
Cancer Epidemiol. Biomarkers Prev.,
July 1, 2004;
13(7):
1163 - 1172.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Mantzoros, E. Petridou, N. Dessypris, C. Chavelas, M. Dalamaga, D. M. Alexe, Y. Papadiamantis, C. Markopoulos, E. Spanos, G. Chrousos, et al.
Adiponectin and Breast Cancer Risk
J. Clin. Endocrinol. Metab.,
March 1, 2004;
89(3):
1102 - 1107.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K.-A. Phillips, R. L. Milne, M. L. Friedlander, M. A. Jenkins, M. R.E. McCredie, G. G. Giles, and J. L. Hopper
Prognosis of Premenopausal Breast Cancer and Childbirth Prior to Diagnosis
J. Clin. Oncol.,
February 15, 2004;
22(4):
699 - 705.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. B. Boyd
Insulin and Cancer
Integr Cancer Ther,
December 1, 2003;
2(4):
315 - 329.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
M. J. Borugian, S. B. Sheps, C. Kim-Sing, I. A. Olivotto, C. Van Patten, B. P. Dunn, A. J. Coldman, J. D. Potter, R. P. Gallagher, and T. G. Hislop
Waist-to-Hip Ratio and Breast Cancer Mortality
Am. J. Epidemiol.,
November 15, 2003;
158(10):
963 - 968.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. B. Boyd
Integrative Tumor Board: Recurrent Breast Cancer or New Primary?
Integr Cancer Ther,
September 1, 2003;
2(3):
270 - 272.
[PDF]
|
 |
|

|
 |

|
 |
 
B. P. Jacobs, B. Burns, R. Marya, J. Chapman, B. Stone, S. Hwang, M. Goldman, K. Barrows, D. Hamolsky, and K. Sampel
Integrative Tumor Board: Recurrent Breast Cancer or New Primary?
Integr Cancer Ther,
September 1, 2003;
2(3):
289 - 300.
[PDF]
|
 |
|

|
 |

|
 |
 
A. S. Fairey, K. S. Courneya, C. J. Field, G. J. Bell, L. W. Jones, and J. R. Mackey
Effects of Exercise Training on Fasting Insulin, Insulin Resistance, Insulin-like Growth Factors, and Insulin-like Growth Factor Binding Proteins in Postmenopausal Breast Cancer Survivors: A Randomized Controlled Trial
Cancer Epidemiol. Biomarkers Prev.,
August 1, 2003;
12(8):
721 - 727.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Goodwin, M. Ennis, K. I. Pritchard, J. Koo, M. E. Trudeau, and N. Hood
Diet and Breast Cancer: Evidence That Extremes in Diet Are Associated With Poor Survival
J. Clin. Oncol.,
July 1, 2003;
21(13):
2500 - 2507.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. McTiernan, K. B. Rajan, S. S. Tworoger, M. Irwin, L. Bernstein, R. Baumgartner, F. Gilliland, F. Z. Stanczyk, Y. Yasui, and R. Ballard-Barbash
Adiposity and Sex Hormones in Postmenopausal Breast Cancer Survivors
J. Clin. Oncol.,
May 15, 2003;
21(10):
1961 - 1966.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. A. Meyerhardt, P. J. Catalano, D. G. Haller, R. J. Mayer, J. S. Macdonald, A. B. Benson III, and C. S. Fuchs
Impact of Diabetes Mellitus on Outcomes in Patients With Colon Cancer
J. Clin. Oncol.,
February 1, 2003;
21(3):
433 - 440.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. H. Schmitz, R. L. Ahmed, and D. Yee
Effects of a 9-Month Strength Training Intervention on Insulin, Insulin-like Growth Factor (IGF)-I, IGF-binding Protein (IGFBP)-1, and IGFBP-3 in 30-50-Year-Old Women
Cancer Epidemiol. Biomarkers Prev.,
December 1, 2002;
11(12):
1597 - 1604.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. L. Rock and W. Demark-Wahnefried
Nutrition and Survival After the Diagnosis of Breast Cancer: A Review of the Evidence
J. Clin. Oncol.,
August 1, 2002;
20(15):
3302 - 3316.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. T. Chlebowski, E. Aiello, and A. McTiernan
Weight Loss in Breast Cancer Patient Management
J. Clin. Oncol.,
February 15, 2002;
20(4):
1128 - 1143.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|