Growing evidence supports the involvement of specific individual fatty acids in mammary carcinogenesis. Polyunsaturated fatty acids of the omega-6 (w6) family, particularly linoleic acid, stimulate tumor proliferation in many cell culture and animal models, and w3 fatty acids can suppress proliferation. Few studies have addressed this in women, and most of those are limited by the measures employed. The proposed study will pool two large breast cancer studies with adipose tissue markers of fatty acid intakes from American and European women to study the effects of fatty acids on tumor occurrence and recurrence. Fatty acid composition of gluteal fat specimens obtained at diagnosis will provide a biomarker of specific fat intake. Analyses from one of the studies suggest that w3 fatty acid intakes and increasing ratios of w3 to w6 fat are protective in European women. The pooled study, with 1400 women, will have enhanced power to analyze effects of the biologically active fatty acids on breast cancer occurrence using populations with wide ranges of intake. Additionally, the 598 cases initially diagnosed with incident breast cancer 6-10 years earlier, will be followed-up to determine whether fatty acid stores influence the recurrence of breast cancer. There are also plans to examine the modifying effects of genetic instability (as measured by p53 and HER-2/neu expression), and estrogen receptor status on the relationship between biologically active fatty acids (as reflected in adipose tissue) and breast cancer in these women. They will also examine whether proliferative capacity of malignant cells (Ki-67 expression as measured by the tumor marker MIB-1) is affected by tissue levels of biologically active fatty acids. Using stratified analyses, the investigators will determine whether this is the case only for estrogen dependent tumors. This multi-center study provides a pooled sample of women with a range of exposures wider than that obtainable from most studies. Direct adipose tissue-based measures of fatty acid stores are available from more individuals than previously assembled in any single study. This will be the first study using biomarkers of prior fatty acid intake with adequate power to assess the potential role of diets rich in w3 fatty acids on the prevention of breast cancer recurrence. It is also uniquely positioned to address the importance of specific tumor characteristics and fatty acids in concert as determinants of breast cancer.
