by Barbara Minton
(The Best Years in Life) Obesity is linked with a huge increase in risk of breast cancer according to several recent studies, and the main culprit appears to be leptin, a hormone secreted by fat cells. This finding applies to women of all ages, not just those who are postmenopausal. A woman’s lipid profile and levels of unbalanced estrogen in conjunction with high body mass index have been shown as additional factors determining whether she gets breast cancer and how deadly it will be.
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Leptin promotes the ability of tumors to establish a blood supply of their own. Once this happens, prognosis becomes less favorable. To determine the mechanism through which this happens, researchers in Atlanta, Georgia studied a mouse mammary model of invasive and highly metastatic breast cancer. They found that leptin induces several signaling pathways to up regulate genetic expression of interleukin-1 (IL-1) in breast cancer cells, leading to the establishment of blood supply in breast tumors.
This research followed a study in Dallas, Texas in which researchers noted that leptin is present at high concentrations in mammary glands of obese women. Their study was designed to determine the role it plays. They found that the local action of leptin within the mammary gland is a critical mediator, linking obesity and dysfunctional fat tissue with aggressive tumor growth.
Scientists in Geneva, Switzerland conducted a population-based study in which they evaluated the impact of obesity on presentation, diagnosis and treatment of breast cancer. Among all women diagnosed with invasive breast cancer in Geneva during a two year period, they identified those with available information on body mass index and categorized them into groups they identified as:
*normal/underweight (body mass index (BMI) <25kg/m),
*overweight (BMI >/=30kg/m)
*obese (BMI >30kg/m)
They compared tumor, diagnosis and treatment characteristics between the groups. They found that obese women presented significantly more often with stage III and stage IV disease, and were 180% more likely to have later stage breast cancer than those women in the normal/underweight group. Women in the obese group were 240% more likely to have tumors that were equal to or greater in size than 1 centimeter compared to the women in the normal/underweight group. And they were a whopping 510% more likely to have positive lymph nodes suggesting their cancers may have spread to other parts of their bodies.
Meanwhile, another team of scientists carried out a comparative study to investigate the effect of lipid profile, unbalanced estrogen in the form of estradiol, and obesity on the risk of a woman developing breast cancer. Assessment of lipid profile, estradiol level and BMI was completed on 100 breast care patients (43 pre and 57 postmenopausal) and 100 controls (45 pre and 55 postmenopausal). Ages ranged from 25 to 80 years.
These scientists found a significant increase in BMI, total cholesterol, triglycerides, and LDL cholesterol in the breast cancer patients compared to the controls. With the exception of estradiol which decreased, the lipid profile generally increased with age in both patients and controls, with the patients having a much higher value than the corresponding controls. There was also a significant positive correlation between BMI and total cholesterol, and between BMI and LDL cholesterol.
Leptin jump starts cancer recurrence
Not only does obesity clearly increase breast cancer risk, but other research in Italy has shown that it shortens the time between return of the disease and lowers overall survival rates. Italian researchers were the first to present evidence that leptin significantly influences breast cancer development, progression and recurrence.
Do you have dysfunctional leptin?
Leptin is best known for its efforts to send messages to the body that it is time to stop eating and begin fat burning. This process may go awry in many people with obesity. Dr. Sebastiano Ando, lead researcher in the Italian study noted that leptin is also involved in many other processes in the breast, from lactation to cell differentiation and proliferation. Leptin is activated by signals from the leptin receptor, and it is this partnership gone wrong that has previously been shown to be involved in the development of breast cancer. Leptin has been found in 86.4% of primary breast tumors.
Previous studies in Dr. Ando’s laboratory found that leptin played a significant role in promoting breast cancer in obese women by increasing the amount of estradiol in breast tissue. His researchers grafted human breast cancer tissue in mice and also created a three dimensional tissue culture closely mimicking biological features of tumors.