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Fat Cells Feed Tumors: the Obesity Risk in Breast Cancer

The number of overweight and obese adults and children has markedly increased over the past several decades. Compared to healthy weight people the obese population is at a greater risk of a number of chronic conditions including diabetes and cardiovascular disease. Recent research has shown a strong link in obese women between being overweight and the occurrence of postmenopausal breast cancer.

Obesity has become an epidemic. In the UK, 67% of men and 57% of women are overweight or obese. According to a study conducted by the Institute for Health Metrics and Evaluation (IHME) in 2010, obesity and being overweight were estimated to cause 3.4 million deaths, 3.9% of years of life lost, and 3.8% of disability-adjusted life-years (DALYs) worldwide. Compared with people of normal weight, those who are overweight or obese are at greater risk of developing many diseases. While a link between obesity and diabetes, high blood pressure, cardiovascular disease, or stroke seems to be commonly recognized, its causal connection to certain types of cancer is less well known to the general public.

What Does Obesity Have to do with Cancer?

UK researchers estimate that, each year, obesity and being overweight are behind around 17,000 cancer cases and with the number of overweight people growing, this figure is bound to increase. The association of obesity with the increased risk of certain cancers could be, at least in part, explained by the ability of fat cells to produce hormones that may stimulate cell growth. Fat cells may also have direct and indirect effects on tumor growth regulators, including mammalian target of rapamycin (mTOR) and insulin-like growth factor-1 (IGF-1) signaling. Obese people often have chronic levels of inflammation, which has been associated with increased cancer risk.

A team of experts at Cancer Research UK has recently analyzed how obesity affects the risk of developing one of seven types of cancer (breast, bowel, pancreas, esophageal, endometrial, kidney, and gallbladder) that had been previously associated with weight. They found that, on average, overweight people have a higher risk of developing one of these forms of cancer in their lifetime. This statistics are particularly alarming for women because some of these cancer types, like breast or endometrial (womb) cancer, only occur in women.

What Do We Know About the Relationship Between Obesity and Breast Cancer?

Two large studies funded by Cancer Research UK, the EPIC study and the Million Women Study, have found that obese women have a 30% higher risk of postmenopausal breast cancer when compared to healthy weight women. This higher risk is mainly seen in women who never used menopausal hormone therapy (MHT) and, importantly, for tumors that express both the estrogen and progesterone hormone receptors. The breast cancer types that rely on estrogen to grow are known as hormone dependent breast cancer and account for about 80% of all breast cancer cases. After menopause the ovaries stop producing estrogen but fat cells can still synthesize it. In overweight women the excess of fat tissues results in higher levels of circulating estrogen, potentially leading to a more rapid growth of estrogen responsive breast tumors.

It is important to note that factors other than obesity can influence a woman’s cancer risk and a controlled clinical trial simply evaluating whether weight loss can decrease the risk of developing any type of cancer could be difficult to implement. For this reason our best clinical strategies still remain early cancer detection or targeted therapy. Hormone dependent breast cancers are treated with antihormonal agents which can produce long periods of remission in early stage breast cancer, however, in the metastatic setting resistance emerges more rapidly meaning suitable models are required to evaluate novel treatments for this disease.

Crown Bioscience has a longstanding track record in breast cancer research with a wide range of research platforms available for all stages of integrated in vitro and in vivo drug development. Our hormone dependent breast cancer resources range from in vitro screening, using the breast cancer OmniPanel collection, to our ValidatedXeno breast cancer cell line derived (CDX) models in which to perform subcutaneous studies, bioluminescent imaging, orthotopic, and metastatic disease evaluation. Many of our in vitro cell lines have an associated in vivo CDX model, allowing seamless transition of your research. We also provide breast cancer patient-derived xenograft (PDX) models within our HuPrime® and PDXact™ collections. Patient-derived xenograft models are recognized as the most predictive preclinical models available for drug evaluation, and our collection of >1,600 PDX provides a diversity of the breast cancer patient population for evaluation of how best to use your agent and identify your target population before you enter the clinic.

Crown Bioscience is committed to developing further models to support breast cancer research and to facilitate the progression of new agents to the clinic. Contact us at busdev@crownbio.com to discover how we can transform your breast cancer research today.

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