Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience

Journal of Experimental & Clinical Cancer Research

Antonio Giordano²  Gennaro Ciliberto⁵  Giuseppe D’Aiuto¹  Tonino Pedicini⁶  Sergio Lodato¹  Giuseppe Brillante¹  Giuseppe Esposito⁴  Ernesta Cavalcanti⁴  Maria Grimaldi⁸  Alfredo Fucito¹  Massimiliano D’Aiuto¹  Nicola Maurea⁷  Anna Crispo⁸  Maurizio Montella⁸  Francesca Pentimalli³  Emanuela Esposito¹  Immacolata Capasso¹ 

[1] Department of Senology, National Cancer Institute, ‘Pascale Foundation’, Via Mariano Semmola, Naples, 80131, Italy;Department of Human Pathology and Oncology, University of Siena, Siena, Italy;INT-CROM, National Cancer Institute, ‘Pascale Foundation’, Cancer Research Center, Via Ammiraglio Bianco, Mercogliano, Avellino, 83013, Italy;Department of Clinical Pathology, National Cancer Institute, ‘Pascale Foundation’, Naples, Italy;Scientific Director; National Cancer Institute, ‘Pascale Foundation’, Naples, Italy;General Director,National Cancer Institute, ‘Pascale Foundation’, Naples, Italy;Department of Cardiology, National Cancer Institute, ‘Pascale Foundation’, Naples, Italy;Department of Epidemiology, National Cancer Institute, ‘Pascale Foundation’, Naples, Italy

关键词: HOMA-IR;    Postmenopausal;    Breast cancer;    Insulin resistance;    Metabolic syndrome;   

Others  :  825336
DOI  :  10.1186/1756-9966-32-14

 received in 2013-01-14, accepted in 2013-03-06,  发布年份 2013

【 摘 要 】

Background

Metabolic Syndrome (MS) has been correlated to breast carcinogenesis. MS is common in the general population (34%) and increases with age and body mass index. Although the link between obesity, MS and hormone related cancer incidence is now widely recognized, the molecular mechanisms at the basis of such increase are still poorly characterized. A crucial role is supposed to be played by the altered insulin signalling, occurring in obese patients, which fuels cancer cell growth, proliferation and survival. Therefore we focused specifically on insulin resistance to investigate clinically the potential role of insulin in breast carcinogenesis.

Methods

975 patients were enrolled and the association between MS, insulin resistance, and breast cancer was evaluated. Women were stratified by age and menopausal status. Insulin resistance was measured through the Homeostasis Model Assessment score (HOMA-IR). The cut off value to define insulin resistance was HOMA-IR ≥ 2.50.

Results

Higher prevalence of MS (35%) was found among postmenopausal women with breast cancer compared to postmenopausal healthy women (19%) [OR 2.16]. A broad range of BMI spanning 19–48 Kg/m² was calculated. Both cases and controls were characterized by BMI ≥ 25 Kg/m² (58% of cases compared to 61% of controls). Waist circumference >88 cm was measured in 53% of cases - OR 1.58- (95% CI 0.8-2.8) and in 46% of controls. Hyperinsulinemia was detected in 7% of cases – OR 2.14 (95% CI 1.78-2.99) and only in 3% of controls. HOMA-IR score was elevated in 49% of cases compared to 34% of controls [OR 1.86], suggesting that insulin resistance can nearly double the risk of breast cancer development. Interestingly 61% of women operated for breast cancer (cases) with HOMA-IR ≥ 2.5 presented subclinical insulin resistance with fasting plasma glucose levels and fasting plasma insulin levels in the normal range. Both android fat distribution and insulin resistance correlated to MS in the subgroup of postmenopausal women affected by breast cancer.

Conclusions

Our results further support the hypothesis that MS, in particular insulin resistance and abdominal fat, can be considered as risk factors for developing breast cancer after menopause. We suggest that HOMA-IR, rather than fasting plasma glucose and fasting plasma insulin levels alone, could be a valuable tool to identify patients with subclinical insulin resistance, which could be relevant for primary prevention and for high risk patient screening.

【 授权许可】

   
2013 Capasso et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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