Obesity, insulin resistance, and poor breast cancer survival

Several new studies published in the Journal of Clinical Oncology provide strong evidence for poor outcomes among women with breast cancer who are obese. In the largest study to date, Ewertz and colleagues followed 18,967 women who were treated for early stage breast cancer between 1977 and 2006. Evaluating recurrence and mortality, the investigators observed that the risk of developing distant metastases was significantly elevated by 46% 10 or more years after diagnosis among both overweight and obese women. Risk of dying from breast cancer was significantly elevated by 38% and from other causes by 31% among obese women 1.
The pathways by which obesity drives recurrence, metastases, and mortality is summarized in an accompanying editorial (see pathway figure). Obese women produce more estrogen from their fat cells, have insulin resistance, and have decreased adipokines and increased IL-6 impacting cell survival 2. The persistent adverse outcomes for breast cancer even in the face of modern treatments has been described previously but is now reinforced by these data. Importantly, the excess morality from other causes attests to the need for more aggressive management of obesity among women with breast cancer.
In other papers published in this issue, the role of insulin resistance in survival after early stage breast cancer was also reported.  Duggan and colleagues followed 527 women with stage I to IIIA breast cancer. Using HOMA as a measure of insulin resistance they show that risk of breast cancer mortality and all cause mortality increased significantly with increasing insulin resistance 3. A measure of insulin section, C-peptide, also related to increased breast cancer mortality and total mortality during follow-up of 604 women with breast cancer 4.
These data together support the pathways summarized by Sinicrope and Dannenberg 2 and clearly support ongoing trials funded by NCI that are evaluating lifestyle interventions to promote physical activity and sustain weight loss among breast cancer survivors. In the mean time, given the proven benefits of sustained weight loss and increased physical activity for prevention of diabetes and improvement of quality of life, it’s time for action to bring these benefits to all women with breast cancer. 
Related CNiC posts

Untapped Benefits of Physical Activity and Weight Loss in Breast Cancer Prevention

Priorities for prevention: breast cancer survivors

Literature cited

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