Breast Cancer Prevention

Basic Sciences

Investigators

Abstract

In our trial of raloxifene in premenopausal women at increased risk for breast cancer, we investigated the safety effects of raloxifene, a selective estrogen receptor modulator. This agent has been recently found to be as effective as tamoxifen in decreasing the risk of invasive breast cancer in postmenopausal women. Overall, we found that raloxifene decreased lumbar spine bone density about 2% per year and hip density less than 1% per year. The loss in bone density stopped when women stopped taking raloxifene. This change is similar to the effect that tamoxifen has on bone in premenopausal women. We also found that raloxifene increased follicular phase serum estradiol and was associated with asymptomatic ovarian stimulation. Women tolerated the agent well and common symptoms on raloxifene included hot flashes, change in menstrual cycle and muscle aches. This is the only long term study of raloxifene in premenopausal women at increased risk for breast cancer. Additionally we determined if IGF-I, IGFBP-3 and leptin are correlated with estrogen receptor status of breast cancer in premenopausal women. Pretreatment serum IGF-I, IGFBP-3 and leptin levels were examined in premenopausal women with breast cancer to determine whether an association with tumor estrogen receptor status exists. One hundred and eight women were evaluated (mean age 42); 82 were ER positive and 26 were ER negative. 62 were normal weight (BMI less than 25) and 46 were overweight or obese (BMI!Y25). Mean IGF-I, IGFBP-3 and leptin levels did not differ between the ER positive and ER negative tumors. No associations were found between IGF-I, IGFBP-3 or leptin and ER status of tumors overall or by subset analysis in normal weight versus overweight and obese individuals. A suggestion that elevated IGFBP-3 was associated with ER-negative disease did not reach statistical significance. Additionally, normal-weight women with ER-negative disease had higher leptin levels than their normal-weight ER-positive counterparts.Our small number of cases suggests a number of intriguing findings that should be evaluated in larger studies. Determining links between ER status and IGFBP-3 and leptin may help better define risk factors and potentially appropriate interventions for ER-negative versus ER-positive breast cancer.