Guinan EM, Connolly EM, Kennedy MJ, Hussey J. The presentation of metabolic dysfunction and the relationship with energy output in breast cancer survivors: a cross-sectional study. Nutri J. 2013;12:99.
Cross-sectional study evaluating the metabolic profile relative to insulin resistance and abdominal obesity
From May 2011 to June 2012, breast cancer survivors from an oncology clinic in Dublin, Ireland were recruited. A total of 69 women met eligible criteria, which was to have completed breast cancer treatment (chemotherapy, radiotherapy, and/or anti-Her-2 biological therapy). The mean time since diagnosis for the group was 3.1 years. Exclusion criteria included active disease and comorbidities such as type II diabetes. Women older than age 70 were also excluded. The average age of the participants was 53.43.
Body composition information including body weight, percentage body fat, and fat-free mass was gathered. Fasting blood samples measured lipid profile, glucose, insulin, glycosylated hemoglobin A1c (HBA1c), and C-reactive protein (CRP). Four groups were created (P<0.05):
- waist circumference < 80 cm (31.50 inches) and not insulin resistant
- waist circumference 80 to 80.9 cm and not insulin resistant
- waist circumference > 80 cm and not insulin resistant
- waist circumference >80 cm and insulin resistant
In breast cancer survivors, women who had both central obesity and insulin resistance were more likely to have poor metabolic profiles including dyslipidemia, low-grade inflammation, and glucose dysregulation. Participants who were centrally obese but not insulin resistant had similar metabolic profiles to the lean participants in this study.
This study further elucidates the need to address a multitude of metabolic factors when working with breast cancer survivors to help them reduce their risk of recurrence. It is now widely accepted that obesity increases risk of breast cancer recurrence and when BMI is reduced to less than 25 kg/m2, risk of recurrence also declines.1 As a result, integrative practitioners are counseling their breast cancer survivors about weight loss.
It is the combination of central obesity and insulin resistance that should be focused on in clinical practice.
This new study confirms a key comorbidity associated with increased breast cancer recurrence risk, and that is insulin resistance. This makes sense because obesity, and specifically central obesity, is linked to insulin resistance.2 Obesity alone can increase risk of breast cancer recurrence by as much as 50%.3 In this study, however, central obesity alone did not confer increased risk of metabolic dysfunction, which demonstrates that it is the combination of central obesity and insulin resistance that should be focused on in clinical practice.
The link between metabolic syndrome and breast cancer recurrence risk is becoming clear. In metabolic syndrome, the visceral adipose tissue is infiltrated by macrophages, and inflammatory cytokines are secreted. These cytokines incite hepatic gluconeogenesis, which, in turn, increases pancreatic secretion of insulin. In this context, there is a potentially hazardous combination of elevated insulin, insulin-like growth factor 1(IGF-1), and inflammatory cytokines. The connection between metabolic syndrome and breast cancer has been confirmed previously. Alokail et al found that patients with metabolic syndrome and elevated triglycerides had an increased risk of breast cancer recurrence (P=0.004).4 Insulin and IGF-1 stimulate cellular proliferation in malignant cells via the constitutively “turned on” insulin receptor (IR) and IGF-1 receptors (IGF-1R). When activated, these receptors activate the PIK3/Akt kinase pathway (also referred to as the insulin pathway), which culminates in mTOR activation. Activated mTOR drives proliferation, alters mitochondrial metabolism toward anabolism (aerobic glycolysis), and decreases apoptosis. Interestingly, some cancers rely exclusively on insulin and IGF-1 for their growth, including an estimated 27% of breast cancers.5 Approximately 8% of these cases6 have constitutive upregulation of the PIK3/Akt pathway.
This study highlights the importance of assessing for metabolic syndrome and insulin resistance in breast cancer survivors for the purpose of reversing this condition. There are a number of therapeutic options available to the integrative practitioner. While a comprehensive discussion of insulin resistance management is too exhaustive for this commentary, some fundamental insulin resistance reduction strategies include following a diet low in or devoid of refined and simple carbohydrates. Additional core strategies to reverse insulin resistance include intermittent fasting,7 adequate sleep or possibly supplemental melatonin,8 magnesium,9 chromium, and cinnamon polyphenols10 Dietary and lifestyle interventions that not only address weight loss but also control and/or reverse insulin resistance are critical when working with breast cancer survivors.
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- O’Neill SC, DeFrank JT, Vegella P, et al. Engaging in health behaviors to lower risk of breast cancer recurrence. PLoS ONE. 2013;8(1):e53607.
- Qatanani M, Lazar MA. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes Dev. 2007;21(12)1443-1455.
- Goodwin PJ. Insulin resistance in breast cancer: relevance and clinical implications. Breast Cancer Res. 2011;13(Suppl2):07.
- Alokail MS, Al-Daghri N, Abdulkareem A, et al. Metabolic syndrome biomarkers and early breast cancer in Saudi women: evidence for the presence of a systemic stress response and/or pre-existing metabolic syndrome-related neoplasia risk? BMC Cancer. 2013;13:54.
- Smith J, Axelrod D, Singh B, Kleinberg D. Prevention of breast cancer: the case for studying the inhibition of IGF-1 actions. Ann Oncol. 2011;22(Supplement 1):i50-i52.
- Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554.
- Harvie MN, Pegington M, Mattson M, et al. The effects of intermittent or continuous energy restriction on weight loss and metabolic disease risk markers: a randomized trial in young overweight women. Int J Obes (Lond). 2011;35(5):714-727.
- McMullan CJ, Schemhammer ES, RimmEB, et al. Melatonin secretion and the incidence of type 2 diabetes. JAMA. 2013;309(13):1388-1396.
- Hata A, Doi Y, Ninomiya T, et al. Magnesium intake decreases Type 2 diabetes risk through the improvement of insulin resistance and inflammation: the Hisayama Study. Diabet Med. 2013 Jun 12. [Epub ahead of print]
- Anderson RA. Chromium and polyphenols from cinnamon improve insulin sensitivity. Proc Nutr Soc. 2008;67(1):48-53.