Estrogen Vindication, Part 3: The Tamoxifen Connection and Hormone Therapy

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By Devaki Lindsey Berkson, DC

Summary

As Part I and Part II of this article explained, estrogen was once an extremely popular hormone. Estrogen replacement was used as an anti-aging drug by multiple millions of women in the United States and all over the world.1 Estrogen therapy was even standard of care to treat certain breast cancers. However, once the Women’s Health Initiative2 (WHI) hormone trials were prematurely stopped due to early negative conclusions (July 9, 2002), claiming prescribed estrogen caused cancer and heart disease, these scary headlines prompted many doctors and women to become estrogen-phobic.

Nonetheless, as crazy as it seems, within only months after the WHI first published negative estrogen news, re-analyses started to emerge from scientists and statisticians at prestigious institutions. These new “look-sees “of the WHI statistical data painted completely different stories.3-15

But the emerging “good news” never made headlines like the initial “bad news.” The bad news? Estrogen can “cause” breast cancer. This turned out to be “wrong news.” The good news: Estrogen therapy in healthy women significantly “protects against” breast cancer.

This good news continued to accumulate over the past two decades, without influencing “standard of care,” without entering the clinical trenches of most doctors or the understanding of most women. Until December 2019.

In December 2019, a 19-year reanalysis16 —looking back from an almost 20-year vantage point with new statistical in-depth collaborative investigation—was presented at the San Antonio yearly breast cancer symposium. Conclusions by a consortium of 12 highly respected cancer centers17 stated—once and for all—estrogen protects breasts. This re-analysis makes it finally undeniable that estrogen is not the enemy; rather, it protects breasts from cancer. Unfortunately, many doctors and women continue to not know about this news nor translate it into their practices or lives.

Even though no one knows exactly how breast cancer starts, it does not seem to be due to estrogen, but rather to cancer stem cells—a totally different kind of cell that has nothing to do with estrogen. Most older women, who naturally have less estrogen, have higher risks of being diagnosed with breast cancer than younger more estrogenized females. Pregnancy, which is the “highest estrogenic time” of life in any woman, is protective against breast cancer. In fact, there is a 70% decrease in breast cancer risk associated with a full-term pregnancy before the age of 18. It’s also been shown that pregnancy is safe after treatment of breast cancer, even among estrogen receptor–positive women patients (ER+ means pathologists identify estrogen receptors in the tumor). Also, no benefits have been proven for abortion at the time of pregnancy in breast cancer patients18 so lowering the levels of estrogen didn’t cause further improvement in outcomes.

The appreciation of estrogen as “foundational” in protecting many aspects of health, is rapidly growing. A few examples are: estrogen protects bones from fracture,19 blood vessels from hardening,20 brain from dementia,21,22 shields mitochondria (energy-producing cells) from damage,23 allows bodies to benefit from lifestyle changes as it promotes epigenetics,24 makes it easier to keep a smaller waistline,25 and maintains heart26 and kidney27-29 health.
Estrogen therapy is as close to an effective anti-aging tool that we have, even maintaining life-promoting telomere length.30 The longer and healthier our telomeres (the tips on our DNA), the longer and healthier we live. In fact, estrogen reduces premature death from quite a large number of possible causes.

Medical practitioners thought tamoxifen worked because it was an anti-estrogen. But, tamoxifen works in a wide variety of anti-cancer mechanisms, not just by tamping down estrogen. In fact, tamoxifen can often raise estrogen levels. Of the 20 studies between 1980 and 2008 that showed estrogen was not only safe for breast cancer patients but was also protective, only the HABITS study found an increased risk of recurrence in breast cancer patients on HRT. This risk only occurred if the women were on tamoxifen, which “blocked” the action of estrogen.31,32

Tamoxifen

A major argument that estrogen causes or promotes breast cancer is that tamoxifen helps to reduce or retard the growth of ER positive breast cancer by competitively blocking the binding of estrogen to the estrogen receptor on breast cancer cells.33 Several lines of research, according to correspondence with Dr. Avrum Bluming, a California oncologist and co-author of Estrogen Matters, dispute this belief.
• When tamoxifen is given to premenopausal women, their natural estrogen levels increase up to five-fold.34
• This rise in estrogen should block any competitive binding of tamoxifen, yet it doesn’t. Tamoxifen’s protective effect against breast cancer works as well in premenopausal as postmenopausal women.35-37
• Approximately 40% of ER+ patients fail to respond to tamoxifen.38
• Cancer is “growth out of control” worsened by “growth factors”. Tamoxifen inhibits growth factor stimulatory effects involved in breast cancer even in the absence of estrogen,39-43 pointing a finger at initiators of breast cancer other than estrogen.
• Estrogen added to tamoxifen, can help make tamoxifen work better. After treatment with tamoxifen, some breast cancer cells acquire the ability to proliferate. These cells become “resistant “ to the protective action of Tamoxifen. But when low doses of estrogen are then given, this helps cancer cells die (apoptosis). Estrogen therapy helps breast cancer cells overcome Tamoxifen resistance, by adding estrogen.44-48
• Tamoxifen has also been shown to have a therapeutic effect on ER negative breast cancer cells, both in laboratory studies and in human patients,49 pointing to other cancer protective effects of tamoxifen than effecting estrogen receptors.

In summary, tamoxifen works through a protective number of portals that have nothing to do with the estrogen receptors. Exactly how Tamoxifen protects against breast cancer isn’t completely known. But it’s inaccurate to say tamoxifen mainly works as an anti-estrogen and thus estrogen is the main drivers of breast cancer.50,51

In 1980, Torbin Palshof from Copenhagen, Denmark, published the results of a study comparing adjuvant estrogen with adjuvant tamoxifen in the management of patients with treated breast cancer.52 From 1975 to 1978, 387 patients who were admitted to three breast cancer clinics in Copenhagen entered the study. Subjects were women younger than 70 years of age, with T1 to T4, N0 to N3, M0 breast cancers. There could be no history of previous or concomitant malignancy. Treatment involved simple mastectomy without routine axillary dissection, and postoperative irradiation. Two weeks after surgery, patients were randomized to double-blind endocrine therapy for two years.