Breast Cancer and Estrogen Therapy: Know the Entire Story

About 80% of all breast cancers are “ER-positive.” That is a massive number of breast cancers related to the hormone estrogen! So it’s no wonder women are often concerned about taking an estrogen hormone replacement.

Interestingly enough, about 80% of women diagnosed with breast cancer each year are aged 45 or older. Pause for a moment. Consider this idea: Breast cancer is most likely to happen during a time when she is supposedly the lowest in estrogen. But isn’t breast cancer linked to estrogen and what is it about this hormone that makes it potentially cancerous?

Why is this? We have to take a step back and understand the entire story.

Estrogens (the class of several different kinds) are a double edge sword. Estrogen is crucial for day-to-day functioning, regulates menstruation, and plays a role in pregnancy, hunger, satiety, and insulin sensitivity. However, estrogen is also involved in the role of cell proliferation and growth. What else involves cell proliferation and growth? Cancer. The events taking place in the precancerous period that are responsible for the evolution of the cancer state show a “growth” phenomenon. To put it simply, estrogen promotes growth. Estradiol is an excitatory hormone that tells our cells to go forth and prosper. For that reason, many gynecological cancers, breast cancer, and liver cancers are recognized as being induced by estrogen. Furthermore, estrogen can be very immunosuppressive when at levels above natural as it can amplify stress in the body. Many studies confirm these associations. For example, “Forty-one women with breast cancer and 119 controls participated in a case-control study of the relation of endogenous sex hormones to breast carcinoma in premenopausal women…Breast cancer was associated with high-plasma estradiol and prolactin and with low progesterone.”

Why does estrogen become off-balance in the first place? Through the aging process, many changes can occur, especially with hormones. Changes in hormone levels often start as early as age 35, and many women experience a loss in progesterone before menopause even starts. What else is going on? Estrogen often rises due to many factors including nutrition, lifestyle, and the environment. In addition, thyroid function often declines with age. If estrogen is too high, it can prevent the thyroid from secreting the thyroid hormone and can also inhibit the conversion of T4 (the inactive form of the thyroid hormone) to T3 (the active form of the thyroid hormone). The aging process also comes with many stressors in life! The more stress an organism is under, the more thyroid dysfunction. As we age, we encounter more stressors. The thyroid will go down because the metabolism needs to reserve energy. The slower metabolism can lead to more fat cells which can synthesize estrogen. This vicious cycle continues and can lead to unbalanced hormones. Stress also causes cortisol to increase. Cortisol activates the aromatase enzyme (used for estrogen biosynthesis) and in the absence of progesterone, cortisol becomes more active, increasing aromatase activity.

So then why do women need estrogen hormone therapy and is it safe?

Menopause correlates to the idea that estrogen has been reduced to not facilitate a menstrual response. It does not mean that all estrogen production is gone. For some women, estrogen does drop in menopause. Usually, a woman that is very petite in size does not have as much estrogen in comparison to a heavier woman. Estrogen continues to be produced in the fat cells and skin cells. In fact, some researchers believe the weight gain that often occurs in older age, may be a way for the body to maintain sufficient estrogen. Therefore, not all women are low in estrogen or need estrogen. Many lab results indicate some menopausal women are still producing sufficient estrogen. Of significant importance is that for most women, progesterone drops significantly 8–10 years before menopause. So while estrogen may be normal or even low, very low levels of progesterone may be connected to breast cancer. This condition is known as estrogen dominance. Progesterone is an estrogen antagonist, an anti-stress hormone, and has many protective benefits in the body. Research shows the better the progesterone levels, the better the body can stop and reverse some cancers. All in all, whether a woman is truly low in estrogen should be determined on an individual basis.

What if you do need estrogen therapy because of very low levels?

There are two types of hormone therapy. One type of hormone therapy (HRT) is made of synthetic hormones. This means that the molecules in the medication are similar, but not identical to, the natural hormone they replace. In order for a medical company to patent a chemical compound, they need to alter the chemical structure of the molecule slightly, so it is different from its natural form.

The Breast Cancer Detection Demonstration produced studies done at Kaiser Permanente Hospital in San Francisco showing that women who were on Premarin (conjugated estrogens) had a rate of endometrial cancer that was five times higher than that of non-users. In conjunction with similar research, these findings rightfully led to HRT’s negative reputation. The Breast Cancer Detection Demonstration Project, part of a nationwide breast cancer screening program, showed estrogen-only hormone replacement therapy increased the overall risk of ovarian cancer by more than threefold.

What about bioidentical estrogens?
One of the most common treatments given to women is bioidentical estradiol. Even though this treatment matches the exact molecule in the body, it doesn’t come without risks. As mentioned, estrogen can have negative side effects on the body including accelerated aging, blood clots, depression, and more. There are often risks when we take a medication. If you’ve ever met someone with extremely low levels of estrogen, she often has severe symptoms. However, sometimes, a woman can truly benefit from estrogen! This is what makes the hormone therapy conversation so tough.

Back to the question of why breast cancer is most likely to happen during a time when she is supposed to have the lowest production of estrogen. Some experts suggest that it’s likely that many tumors begin a minimum of five years before they are detected. So what happened to your hormones the five to ten years before menopause? Exposure to estrogen could have been high for many years, before dropping in menopause.

Furthermore, the most commonly tested estrogen is estradiol. This is because estradiol is the principal intracellular human estrogen and is substantially more active than its metabolites, estrone, and estriol, at the cellular level. However, estradiol is still not the only relevant estrogen. Per Wikipedia, although E1S (estrone sulfate) is biologically inactive, with less than 1% of the relative binding affinity of estradiol for the ERα and ERβ, it can be transformed by steroid sulfatase, also known as estrogen sulfatase, into estrone, an estrogen. The same goes for E1 (estrone). E1 and E1S can rise during menopause and both of these estrogens can be converted into estradiol in tissues. Although most lab tests do not measure E1 and ES, body fat may predict these levels. A recent study showed that “plasma levels of E1 and E1-S were positively associated with BMI and total body fat mass. A positive association was also found between E1-S and percent body fat.” To summarize, estradiol is not the only relevant estrogen, despite it being the most commonly tested biomarker because the total body estrogen can be derived from peripheral aromatization.

Another reason why breast cancer may happen during a time when estrogen is supposedly low is that the concentrations of estrogens in serum, saliva, or urine may be different than the concentration in the tissues. One study concluded that “despite the low levels of circulating estrogens in postmenopausal patients, the tissue concentrations of these steroids are several-fold higher than those in plasma, suggesting tumor accumulation of these estrogens. The physiopathology and clinical significance of these high levels of the various estrogens (E1, E2, and E1S) as well as sulfatase and aromatase activities in postmenopausal patients with breast cancer is yet to be explored.” Our skin is one of the central organs known to contain circulating levels of estrogen hormones. Receptors for the estrogen hormones are located in both the epidermal and dermal layers, as well as in the blood vessels of the skin. Estrogen concentrations in tissues often correlate positively with aging and with body fat levels. Blood levels of estrogen do not necessarily reflect tissue concentrations of estrogen. Increased by estrogen, prolactin often becomes excessive around menopause, slows the metabolic rate, and inhibits the production of progesterone.

To recap:

• Estrogen has potentially carcinogenic effects and this may be why NIH lists estrogen therapy as a carcinogen.
• Bioidentical therapy, despite being “natural,” can still come with the same side effects as synthetic estrogen therapy given estrogen’s proliferative actions.
• Some women, but not all women do need estrogen therapy, because their levels have dropped significantly in menopause. Risks of estrogen’s negative side effects can be mitigated with estrogen antagonists like progesterone and pregnenolone.
• Although estrogen can drop during menopause, progesterone often drops faster 8–10 years before menopause. This off-balance ratio may contribute to breast cancer.
• Breast cancer takes years to develop. Despite estrogen level production decreasing from the ovaries during menopause, what happened the ten years before menopause?
• Biomarkers like estrone and estrone sulfate are not commonly tested but may be significant biomarkers in the connection to breast cancer.
• The serum concentration of estrogen does not always match the tissue concentration.

What can you do?
At Moment, we work with doctors that optimize YOUR unique hormone balance. To mitigate the risks of estrogen supplementation, we often use substances that oppose estrogen. These treatments most often include progesterone and pregnenolone. Progesterone and pregnenolone are aromatase inhibitors and can help to keep the estrogen hormones balanced. However, you are unique and so is your treatment plan! Head to www.momenthealth.co to learn more.