It has long been known that weight gain in the post-menopausal years increases the risk of breast cancer. But this clinical observation lacked a solid scientific explanation. Previous experiments revealed high levels of estrogen and insulin in overweight post-menopausal patients developing breast cancer. Recently, scientists also demonstrated presence of leptin (a substance associated with obesity) in normal breast tissue and in the breast cancer cell lines of obese post-menopausal females. The presence of this obesity-related protein in breast cancer tissue lends further credence to the observation of linkage between obesity and breast cancer.
But no specific mechanism of action was elucidated until recently. Scientists from the Hormel Institute at the University of Minnesota showed enhanced growth and malignant transformation in breast cancer cell lines when leptin was added. They further demonstrated leptin receptors through which its effect is transduced. In two separate cell lines, augmented growth, varying from 60 percent to 160 percent, was demonstrated with the addition of leptin.
To further strengthen their observation, they crossed a strain of mice that have high genetic potential of breast cancer with mice that are genetically engineered and rendered incapable of producing leptin and leptin receptors and demonstrated that none of the mice developed breast cancer. This experiment concludes that leptin is at least one of the essential requirements for the process of carcinogenesis in the breast.
This gives a simple explanation of how obesity enhances breast cancer risk. The clinical implication is that post-menopausal weight gain is undesirable and that weight control may have a protective effect. Such protection also may be realized in premenopausal women. Even more important is the distinct possibility of drug development to inhibit leptin binding and subtracting leptin's role in breast cancer development. Whether this will have a meaningful impact on breast cancer incidence, only time will tell. But the possibility seems good.
_ V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.