Dietary Fat, Eicosanoids and Breast Cancer Risk

The guiding concept of our proposal is that both the total fat and the fatty acid composition
of the diet contribute to a milieu associated with the risk for sex-hormone mediated cancers.
Specifically, we hypothesize that an increased concentration of circulating n3 fatty acids
will reduce the biochemical markers associated with increased risk for developing certain sex
hormone mediated cancers such as breast cancer. When compared with the high fat diet, we
expect n3 concentrations to increase and sex hormone levels to decrease after both low fat
and low fat/n3 rich diets, with the greatest response in the low fat-n3 supplemented group.
The aims of this project are: 1) to evaluate the effects of total fat and n3 fatty acid
consumption on plasma and urine sex hormone concentrations in postmenopausal women, 2) to
evaluate the relationship between plasma concentrations of fatty acids and plasma and urinary
sex hormone concentrations, and 3) to evaluate the effects of total fat and n3 fatty acid
consumption on the associations between sex hormone concentrations and urinary prostaglandin
E2 and thromboxane B2 concentrations.

The primary objective of this investigation is to determine whether diets designed to
increase plasma n3 concentrations (a low fat diet, with or without n3 fatty acid enrichment),
will favorably affect sex hormone distribution in women in a direction associated with
reduced risk of sex hormone-mediated cancer development. The primary endpoints to be
evaluated include plasma and urinary sex hormone concentrations as follows:

Endpoints associates with increased risk factors for breast cancer risk: plasma estradiol
(E2), estrone (E1), estrone sulfate (E1 sulfate), testosterone, androstenedione, sex hormone
binding globulin (SHBG), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate
(DHEAS), Measures of estrogen action: plasma follicle stimulating hormone (FSH), urinary
estrogen metabolites.

Measures of systemic arachidonic acid-derived eicosanoids: urinary bicyclo-prostaglandin E2
(PGEa), 2,3-dinor thromboxane B2 (TXB2).

Measures reflecting influence of dietary fat and fatty acid intake: plasma phospholipid,
cholesterol ester, triglyceride and free fatty acid composition.

Inclusion Criteria:

- Postmenopausal women

- 45 to 70 years old,

- at least one year since their last menstrual period

- not using hormone replacement therapy,

- BMI between 19 -29

- willingness to discontinue use of over-the-counter medications with anti-prostaglandin
activity such as aspirin or non-steroidal anti-inflammatory medications

- consumption of a "Typical " American diet with no unusual dietary practices such as
compliance with a strict vegetarian diet

- willingness to comply with the demands of the experimental protocol.

Exclusion Criteria:

- Smoking

- Known disease process, and 3) Use of prescription medications, including hormone
replacement therapy.