Insulin resistance is a risk factor for breast cancer even with normal fasting glucose and insulin

Well before fasting glucose and insulin rise out of the normal range, background surges of insulin associated with decreased insulin receptor sensitivity do harm throughout the body and, as confirmed by a study just published in the Journal of Experimental & Clinical Cancer Research shows, promote breast cancer. The authors observe:

"Metabolic Syndrome (MS) has been correlated to breast carcinogenesis [development of breast cancer]. 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 cancers incidence is now widely recognized, the molecular mechanisms at the basis of such increase are still poorly characterized. 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."

They investigated the role of insulin resistance in the development of breast cancer by examining data for 975 women, specifically measuring insulin resistance with the Homeostasis Model Assessment score (HOMA-IR) in 975 women. Using the cut off value HOMA-IR >= 2.50 to define insulin resistance there was a clear connection:

"Higher prevalence of MS [metabolic syndrome] (35%) was found among postmenopausal women with breast cancer compared to postmenopausal healthy women (19%). 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 and in 46% of controls. Hyperinsulinemia was detected in 7% of cases and only in 3% of controls. HOMA-IR score was elevated in 49% of cases compared to 34% of controls. That means 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."

Practitioners should savor the significance of this: (1) insulin resistance nearly doubles the risk of breast cancer; (2) breast cancer-promoting insulin resistance can be subclinical, that is with normal fasting glucose and insulin. The authors elaborate:

"Insulin resistance can often be defined as a subclinical condition. Consistently, most of our patients (68%) had levels of fasting plasma glucose in the normal range, and, interestingly, only through the use of HOMA score we classified them as insulin resistant. Similarly, fasting plasma insulin levels were diagnosed as normal in 88% of cases. These patients were identified as insulin resistant only by means of the HOMA score. HOMA-IR is widely-used in epidemiologic studies as a measure of insulin resistance, and has been shown to reflect euglycemic clamp insulin resistance more accurately than fasting insulin levels alone."

Their conclusions are of the first importance for the prevention of breast cancer:

"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 patients screening...In conclusion, our experience suggests that insulin resistance and abdominal fat (more than BMI alone) represent the most important criteria of MS on which primary prevention should be concentrated. Interestingly, Homeostasis Model Assessment of insulin resistance promises to be a valuable tool for primary prevention, particularly for patients with subclinical insulin resistance, presenting fasting plasma glucose levels and fasting plasma insulin levels in the normal range. Our findings suggest that HOMA-IR could be useful in screening patients at higher risk of developing breast cancer.

Clinicians wishing to calculate model-derived estimates of insulin sensitivity and beta cell function derived from fasting plasma glucose and insulin can use the HOMA2 Calculator made available by the University of Oxford Centre for Diabetes, Endocrinology and Metabolism.