Breast Cancer Risk Factors to Look For on the DUTCH Test

Know the Risk Factors 

Knowing the risk factors for breast cancer may be helpful, considering that breast cancer is the most common cancer diagnosed in women (apart from skin cancer), and the second leading cause of cancer death in women overall (second to lung cancer). This blog aims to shed light on the factors that increase one’s risk for breast cancer and to discuss how DUTCH testing can be utilized to mitigate some of these risks. 

Concerned Female at Laptop with Logo and Breast Cancer Ribbon

Some Breast Cancer Risk Factors are Outside of Your Control 

Genetic mutations

  • Only 5-10% of breast cancers are thought to be hereditary. Hereditary breast cancers are most commonly due to BRCA1 and BRCA2 gene mutations. 

Personal history of breast cancer

  • If a woman has already had breast cancer, she has a higher chance of developing cancer in the opposite breast, or in a different part of the same breast. 

Family history of breast cancer

  • A woman’s risk is almost twofold if they have one first-degree relative (mother, daughter, sister) with breast cancer and threefold if they have two first-degree relatives with breast cancer. Note, however, that most women who get breast cancer have no family history of the disease.   

White and black ethnicity

  • Overall, breast cancer is slightly more common in white women than black women. However, in women younger than 40, it is more common in black women. Black women die from breast cancer more often than white women. This may be because black women are more likely to have triple-negative breast cancer that is less responsive to treatment, but it is also likely due to racial and ethnic healthcare disparities. 

Starting menstrual periods early and/or going through menopause later

  • This may be due to the increased amount of time that one is exposed to endogenous hormones. 

Other risk factors that are outside of your control include dense breasts, tall stature, radiation to the chest, exposure to DES, benign breast disease, female sex, and older age. 

Other Breast Cancer Risks May be Within Your Control 

Overweight or obesity in menopause, insulin resistance and sedentary lifestyle:

  • All these factors increase a woman’s risk for breast cancer. The American Cancer Society recommends 150 to 300 minutes of moderate intensity or 75 to 100 minutes of vigorous intensity (or combination of these) each week. 

High endogenous estrogen:

  • Higher endogenous estrogen levels increase risk for breast cancer in both pre-menopausal women and post-menopausal women. 

High endogenous androgens:

  • The link between androgens and breast cancer is not clear. Higher endogenous androgens may increase risk for breast cancer, possibly indirectly through aromatization to estrogen. However, androgens may also play a role in decreasing risk for breast cancer through their anti-estrogenic and anti-proliferative effects via androgen receptor signaling. 

Other risk factors include not having children or having children at an older age (≥35), not breastfeeding, alcohol, smoking, oral birth control, and breast implants.  

Is Menopausal Hormone Therapy (MHT) a risk factor for breast cancer?

Synthetic hormones may slightly increase a woman’s risk for breast cancer; however, this risk is minimized by using transdermal bioidentical estradiol and oral or vaginal micronized bioidentical progesterone. For more information, check out Dr. Doreen Saltiel’s DUTCH Blog article “Menopausal Hormone Therapy, Breast Cancer and Mortality: The Same Story on a Different Day”.

Key DUTCH Markers for Breast Cancer 

When it comes to assessing (and lowering) breast cancer risk, the following are patterns to look out for on the DUTCH Test. Note that when these DUTCH Test markers are out of range it does not necessarily indicate that breast cancer is present or that someone will develop breast cancer in the future. When interpreting DUTCH Test results, also take the individual’s family history, personal history, current health status, and genetics, etc. into consideration. 

Estrogen Excess and “Estrogen Dominance” 

The DUTCH Test measures nine estrogen related markers: estrone (E1), estradiol (E2), estriol (E3), five Phase I estrogen metabolites (2-OH-E1, 2-OH-E2, 4-OH-E1, 4-OH-E2, 16-OH-E1) and one Phase II estrogen metabolite (2-methoxy-E1). If any of these markers are elevated, it may be a sign of estrogen excess.  

Elevated Androgens

The DUTCH Test measures seven androgen related markers: testosterone, 5a-DHT, 5a-androstanediol, 5b-androstanediol, DHEA-S, etiocholanolone and androsterone. The marker 5a-DHT is the active form of testosterone, however urinary 5a-androstanediol may be a better indicator of androgen activity in the tissues than urinary 5a-DHT. The DUTCH Test measures both markers. 

Poor Phase I and Phase II Estrogen Detoxitication 

It turns out that how one metabolizes their estrogen is extremely important when it comes to breast cancer risk. The DUTCH Test measures five Phase I metabolites (2-OH-E1, 2-OH-E2, 4-OH-E1, 4-OH-E2 and 16-OH-E2). Individuals with elevated 2-OH and 4-OH metabolites may have an increased risk for breast cancer. This is because these estrogen catechols can become reactive quinones that cause DNA damage directly in the breast tissue. The 4-OH catechols tend to cause more DNA damage than the 2-OH catechols, however. The metabolite 16-OH-E1 is thought to have proliferative effects on estrogen receptors and thus 16-OH-E1 may cause an ER+ breast cancer to grow more quickly. For more information check out Dr. Kelly Ruef’s DUTCH case study “Elevated 4OH & Breast Cancer Risk”. 

The DUTCH Test also measures one Phase II metabolite, 2-methoxy-E1. We can compare the ratio between 2-methoxy-E1 and 2-OH-E1 to get an idea of methylation activity. Low methylation activity may cause the 2-OH and 4-OH estrogen catechols to build up in Phase I, thus increasing risk for reactive quinone formation and DNA damage. For more information regarding additional workup when low methylation activity is found on the DUTCH Test, check out Dr. Kelly Ruef’s DUTCH case study “Explaining Methylation on the DUTCH Test”.

Flat Cortisol Slope and/or High Nighttime Cortisol Levels 

Women with metastatic breast cancer who also have a flattened cortisol slope may experience earlier mortality. The DUTCH Test measures free cortisol and cortisone throughout the day and thus enables one to identify if there is a flat curve, or if the nighttime cortisol is elevated. 

Low Melatonin 

One study showed that as urinary melatonin went down, risk for breast cancer went up. This may be because melatonin is a powerful antioxidant and is important for sleep/wake cycles. 

Low or High Pyroglutamate 

Pyroglutamate is a glutathione marker. Glutathione plays an important role in cancer prevention by quenching the downstream reactive quinones of 4-OH and 2-OH estrogen catechols that contribute to DNA damage in breast tissue. 

High 8OHdG 

8OHdG elevates when there is significant DNA damage due to oxidative stress. It can be elevated in cancers, but also in other situations that involve elevated inflammation levels. 

One in eight women has a chance of developing breast cancer in her lifetime.

The good news is that there are various risk factors for breast cancer that you have some control over, and the DUTCH Test can provide insight into some of these risk factors.  

For more information, check out Dr. Carrie Jones’ DUTCH Webinar “Breast Cancer Insights: Important Markers to Watch using the DUTCH Test” and Dr. Tara Scott’s recent DUTCH webinar “An Integrative Approach to Breast Cancer.”