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

Immacolata Capasso1*, Emanuela Esposito1, Francesca Pentimalli2, Maurizio Montella3, Anna Crispo3, Nicola Maurea4, Massimiliano D’Aiuto1, Alfredo Fucito1, Maria Grimaldi3, Ernesta Cavalcanti5, Giuseppe Esposito5, Giuseppe Brillante1, Sergio Lodato1, Tonino Pedicini6, Giuseppe D’Aiuto1, Gennaro Ciliberto7 and Antonio Giordano289*

Author Affiliations

1 Department of Senology, National Cancer Institute, ‘Pascale Foundation’, Via Mariano Semmola, Naples, 80131, Italy

2 INT-CROM, National Cancer Institute, ‘Pascale Foundation’, Cancer Research Center, Via Ammiraglio Bianco, Mercogliano, Avellino, 83013, Italy

3 Department of Epidemiology, National Cancer Institute, ‘Pascale Foundation’, Naples, Italy

4 Department of Cardiology, National Cancer Institute, ‘Pascale Foundation’, Naples, Italy

5 Department of Clinical Pathology, National Cancer Institute, ‘Pascale Foundation’, Naples, Italy

6 General Director,National Cancer Institute, ‘Pascale Foundation’, Naples, Italy

7 Scientific Director; National Cancer Institute, ‘Pascale Foundation’, Naples, Italy

8 Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, BioLife Science Bldg. Suite 333 1900 N 12th Street, Philadelphia, PA, USA

9 Department of Human Pathology and Oncology, University of Siena, Siena, Italy

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Journal of Experimental & Clinical Cancer Research 2013, 32:14  doi:10.1186/1756-9966-32-14

Published: 14 March 2013

Abstract

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.

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