title: Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience.
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.
authors.affiliation: Department of Senology, National Cancer Institute, 'Pascale Foundation', Via Mariano Semmola, Naples, 80131, Italy. icapasso@tiscali.it
authors.forename: Immacolata
authors.initials: I
authors.lastname: Capasso
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Francesca
authors.initials: F
authors.lastname: Pentimalli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Montella
authors.forename: Anna
authors.initials: A
authors.lastname: Crispo
authors.forename: Nicola
authors.initials: N
authors.lastname: Maurea
authors.forename: Massimiliano
authors.initials: M
authors.lastname: D'Aiuto
authors.forename: Alfredo
authors.initials: A
authors.lastname: Fucito
authors.forename: Maria
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Ernesta
authors.initials: E
authors.lastname: Cavalcanti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Esposito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Brillante
authors.forename: Sergio
authors.initials: S
authors.lastname: Lodato
authors.forename: Tonino
authors.initials: T
authors.lastname: Pedicini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Aiuto
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ciliberto
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D007558:Italy; D024821:Metabolic Syndrome / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D007328:Insulin