Breast Cancer Risk THE ROLE OF ESTROGEN METABOLITES

Based on current estimates, 12.4 percent of women born in the United States today will develop breast cancer at some time during their lives. This means, if the current incidence rate stays the same,
a woman born today has about a 1 in 8 chance of being diagnosed with breast cancer at some time during her life.
Hormone balance is one of the most common reasons women seek care in my office. As an Integrative and Functional Medicine physician, my role is to provide effective testing and assessment of hormone imbalance, and outline personalized recommendations to reduce my clients’ risks. I use estrogen metabolite testing to evaluate and assess Breast Cancer risk.
BREAST CANCER RISK FACTORS When examining your potential risk for developing Breast Cancer, a variety of factors should be taken into consideration.
There are some risk factors for Breast Cancer that are out of your control, such as:
- genetic variants/gene mutations
- family history
- reproductive history
- high-dose radiation exposure to the chest
Other risk factors for Breast Cancer you have more control over and are modifiable:
- high endogenous estrogen (elevated levels of estrogen in the body)
- hormone therapy
- obesity
- alcohol consumption
Estrogen metabolites are additional factors that can be measured in your urine and considered when evaluating Breast Cancer risk. Estrogen metabolites are formed when estrogen is metabolized through your liver. This process is influenced by a combination of your genetics and environment. The type of estrogen metabolites that you produce in your body may have an impact on your Breast Cancer risk.
ESTROGEN METABOLITES Which path does estrogen take in your body?
- Estrogen metabolites are formed when estrogens are metabolized through your liver.
- There are different types of estrogen metabolites, and certain types may be associated with a higher risk of Breast Cancer.
- The types of estrogen metabolites that are produced in your body are impacted both through genetic and lifestyle factors.
Estrogen metabolites are formed when estrogens are processed through your liver. All estrogen is metabolized in your body through pathways in your liver. It doesn't matter if the estrogen is made in your body (from your ovaries or through conversion in your fatty tissues) or if you are taking estrogen in from the outside (whether intentionally through hormone therapy or birth control pills or unintentionally through xenoestrogens in the environment). It all gets processed, or metabolized, in this way.
There are different types of estrogen metabolites, and certain types may be associated with a higher risk of Breast Cancer.
Think of estrogen being metabolized through the liver like it is traveling along a complicated map route. There are a number of factors that affect the route it takes, and different routes produce different estrogen metabolites.
The three key estrogen metabolites measured and their relative risk of Breast Cancer include:
Estrogen Metabolite Association with Breast Cancer Risk 2-hydroxyestrone (2-OHE1) lower risk
16 alpha-hydroxyestrone (16a-OHE1) higher risk
4-hydroxyestrone (4-OHE1) highest risk
2-hydroxyestrone (2-OHE1) binds very weakly to target tissues, and has even been shown to have anti-estrogen properties. In contrast, 16 alpha-hydroxyestrone (16a-OHE1) is a powerful metabolite that stimulates target tissues. High levels of this potent metabolite are linked to increased risk and poorer prognosis in conditions linked to estrogen excess such as breast cancer and lupus. It is desirable to have a higher ratio of 2-OHE1 to 16a-OHE1 metabolites.
4-hydroxyestrone (4-OHE1) is considered a “bad” estrogen metabolite because it can easily convert to compounds that directly damage DNA, potentially increasing risk for initiation of Breast Cancer.
The types of estrogen metabolites that are produced in your body are impacted both through genetic and lifestyle factors. If you have a genetic variant in one or more of these pathways, this can affect your ratio of estrogen metabolites and impact your risk of Breast Cancer.
Estrogen Metabolite Genetic Pathway 2-hydroxyestrone (2-OHE1) CYP1A1
16 alpha-hydroxyestrone (16a-OHE1) CYP3A4
4-hydroxyestrone (4-OHE1) CYP1B1
Diet and lifestyle patterns also affect which types of estrogen metabolites are produced in your body. Factors that are known to promote a healthier estrogen metabolite ratio and lower risk of Breast Cancer include:
- higher intake of cruciferous vegetables, lignans (flax seed) and whole soy
- reduction of body fat
- reduction of exposure to pesticides
- reduced intake of alcohol
- higher omega-3 fatty acid intake
- regular exercise
DETERMINING ESTROGEN'S PATH IN YOUR BODY. In my office, I measure estrogen metabolites primarily through the urine (there is a report example below). In premenopausal women, this is done with a first-morning urine on day 21 of the menstrual cycle. In postmenopausal women, this is done with a 24-hour urine collection. The test can be repeated to follow-up targeted lifestyle therapies and supplement protocols.

I use an Integrative/Functional Medicine approach with my patients to treat a variety of chronic medical conditions, including many that are linked to unhealthy hormone imbalance. Treating symptoms simply by prescribing medication as a “band-aid” does not address the underlying factors that contributed your problems in the first place, and is not likely to provide lasting results. My approach involves getting "under the surface” (using assessments like estrogen metabolite testing) to find and correct underlying imbalances. If you are interested in learning more or if you would like to schedule a consultation, please contact our office This email address is being protected from spambots. You need JavaScript enabled to view it. or 231-638-5585.