Phytoestrogen intake and risk of advanced breast cancer
Principal Investigator
Name
Michael Reger
Degrees
Ph.D., M.P.H.
Institution
University of Notre Dame
Position Title
Principle Investigator
Email
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
PLCO-1642
Initial CDAS Request Approval
Aug 9, 2024
Title
Phytoestrogen intake and risk of advanced breast cancer
Summary
Breast cancer (BC) is one of the highest incident cancers and leading causes of cancer mortality in women globally [9]. Non-modifiable risk factors such as family history, age, and reproductive factors have been previously established [7], however the discovery of modifiable factors that may modulate the risk of the development of BC is still ongoing [4,8].
Phytoestrogens (PE) are plant-derived compounds with structural similarity to 17-B estradiol, and therefore can bind to estrogen receptors and potentially influence BC development [2]. These non-steroidogenic compounds are commonly found in soy products, legumes, oils, flaxseeds, whole grains, nuts, vegetables, and fruits [6]. Women in Asian countries average a higher consumption of dietary soy compared to Western countries, and also have lower BC incidence and mortality. Therefore it is hypothesized that consuming more soy and PE in Western diets may decrease the risk of BC [6].
Previous studies have analyzed the dietary impact of PE intake on the development of receptor and progesterone-dependent/independent BC [3], demonstrated protective benefits of PE for post-menopausal women [1], and demonstrated non-statistically significant associations between BC and PE [1]. These mixed results have yet to produce a recommendation for soy consumption to reduce the risk of BC. A small total sample size and overall number of BC patients in many previous studies has prevented the differentiation of risk between PE intake and advanced and non-advanced BC. Total dietary PE consumption could influence risk for developing advanced BC, and metastasis could be affected by the receptor binding of circulating PE. The determination of the relationship between PE intake and advanced and non-advanced BC could lead to preventive and cost-effective strategies to reduce BC risk.
This study will utilize the PLCO data to evaluate the relationship between PE intake and total, non-advanced, and advanced BC cases separately using Chi-square, t-test, and Cox proportional hazards regression. Advanced BC will be classified as Stage III or IV, and non-advanced will be classified as Stage I or II. Potential confounding variables associated with breast cancer risk from previous studies will be tested for significance and included in the final regression model if they alter the risk estimates greater than 10%. These variables include, but are not limited to age, race, BMI, waist-to-hip ratio, physical activity, smoking, alcohol, energy intake, dietary intake of saturated fat, protein, carbohydrates, and sugar, age of menarche, pregnancies, age at delivery, parity, age at menopause, hysterectomy, menopausal status, familial history of breast cancer, oral contraceptive use, and hormone replacement therapy.
Phytoestrogens (PE) are plant-derived compounds with structural similarity to 17-B estradiol, and therefore can bind to estrogen receptors and potentially influence BC development [2]. These non-steroidogenic compounds are commonly found in soy products, legumes, oils, flaxseeds, whole grains, nuts, vegetables, and fruits [6]. Women in Asian countries average a higher consumption of dietary soy compared to Western countries, and also have lower BC incidence and mortality. Therefore it is hypothesized that consuming more soy and PE in Western diets may decrease the risk of BC [6].
Previous studies have analyzed the dietary impact of PE intake on the development of receptor and progesterone-dependent/independent BC [3], demonstrated protective benefits of PE for post-menopausal women [1], and demonstrated non-statistically significant associations between BC and PE [1]. These mixed results have yet to produce a recommendation for soy consumption to reduce the risk of BC. A small total sample size and overall number of BC patients in many previous studies has prevented the differentiation of risk between PE intake and advanced and non-advanced BC. Total dietary PE consumption could influence risk for developing advanced BC, and metastasis could be affected by the receptor binding of circulating PE. The determination of the relationship between PE intake and advanced and non-advanced BC could lead to preventive and cost-effective strategies to reduce BC risk.
This study will utilize the PLCO data to evaluate the relationship between PE intake and total, non-advanced, and advanced BC cases separately using Chi-square, t-test, and Cox proportional hazards regression. Advanced BC will be classified as Stage III or IV, and non-advanced will be classified as Stage I or II. Potential confounding variables associated with breast cancer risk from previous studies will be tested for significance and included in the final regression model if they alter the risk estimates greater than 10%. These variables include, but are not limited to age, race, BMI, waist-to-hip ratio, physical activity, smoking, alcohol, energy intake, dietary intake of saturated fat, protein, carbohydrates, and sugar, age of menarche, pregnancies, age at delivery, parity, age at menopause, hysterectomy, menopausal status, familial history of breast cancer, oral contraceptive use, and hormone replacement therapy.
Aims
Aim 1: The primary aim of this study is to evaluate the association between total PE intake and the risk of total, non-advanced, and advanced BC.
Hypothesis: Increased dietary intake of PE is associated with a statistically significant decreased risk of advanced BC.
Aim 2: To determine the BC risk associated with the different classes and individual PEs.
Hypothesis: Total and individual isoflavones are associated with a greater decreased risk of advanced BC due to the higher concentrations found in common foods.
Collaborators
Sydney Maxey - University of Notre Dame