Posts Tagged ‘side effects of aromatase inhibtors’

Could the Natural Alternative to Tamoxifen and Aromatase Inhibitors be in Your Refrigerator? Part II

In Alternative Cancer Therapies, Alternatives Cancer Treatment, Alternatives to Anti-Hormone Therapy For Breast Cancer, Alternatives to Hormone Therapy for Breast Cancer, Alternatives to Tamoxifen, Anticancer foods, foods for colon cancer, foods for breast cancer, antioxidants, aromatase inhibitors, BPA and breast cancer, Breast Cancer, Cancer, Cancer Coach, cancer stem cells and recurrence, Estrogen, Estrogen and Breast Cancer, Natural Aromatase Inhibitors, prostate cancer, SERMS, Tamoxifen, Uncategorized on November 15, 2019 at 9:07 am

Synthetic selective estrogen receptor modulators (SERMS) such as tamoxifen and pharmaceutical aromatase inhibitors are often recommended for ER+ breast and other hormone-driven cancers, but they have significant adverse effects. Is it possible that natural plant products can perform the same function without the risks and damage of pharmaceuticals? Research says they can.

While estrogen plays many important beneficial roles in humans, the proliferation of ER+ breast cancer cells can sometimes be enhanced by estrogen (especially in the absence of progesterone), which may induce multiple processes involved in cell survival and cell cycle progression. Beyond the estrogen dominance that comes from a lack of progesterone, it is not necessarily our own estrogen at fault, but more likely xenoestrogens — the chemical estrogens, environmental hazards such as BPA and BPS — Bisphenol A and S.

However, to add clarity to the estrogen equation that oncologists speak of, the body has two different estrogen receptors, ERα (alpha) and ERβ (beta). ERα has a proliferative effect, and ERβ acts as a negative regulator of ERα in breast cancer cells, counteracting the proliferative effect of estrogens. Importantly, plant estrogens (phytoestrogens) preferentially interact with ERβ and display high specificity toward ERβ transactivation. Phytoestrogens, also known as phytochemicals, are synthesized from plants and vegetables. They show low estrogenic activity or anti-estrogenic activity with anti-proliferative effects that studies show offer nutraceutical alternatives to pharmaceutical anti-hormone therapies for various cancers.[ii]

For the men reading this article (including those with breast cancer), androgens and estrogens also influence the development and progression of prostate cancer. Research shows that phytoestrogens such as soy could be used alone or in conjunction with anti-hormone therapies for prostate cancer to target metabolic pathways involved in androgen and estrogen syntheses and epigenetic modifications of DNA to promote tumor-suppressor genes.[iv]

In a nutshell, phytoestrogens may be useful as substitutes for breast cancer treatments such as tamoxifen or aromatase inhibitors, and could be extremely helpful for other hormone-related cancers.

The Role of Phytoestrogens as Replacements for SERMs and Aromatase Inhibitors

It is well-established that many foods and natural products have beneficial effects on ER+ breast cancer as well as other hormone-driven cancers.  Pytoestrogens are structurally similar to our own estrogen, but functionally are weakly estrogenic (weakly mimicking estrogen) or antiestrogenic (blocking estrogens’ effects). They have been researched extensively for their role in the interaction with estrogen receptors. The beauty is that they block the receptors from more volatile estrogens.  As such, they deserve consideration in preventive and therapeutic settings for the intervention of cancer initiation and progression.

Studies show that phytoestrogens may provide an alternative or complementary approach to anti-hormone treatments. For example, 2017 research published in the International Journal of Molecular Sciences cited many studies confirming that an important application of phytoestrogens is that they could be used as an alternative to the SERMs.[iii] In general, phytoestrogens act as aromatase inhibitors by decreasing aromatase gene expression and inhibiting the aromatase enzyme.   

Some of the more powerful phytoestrogens include flax and sesame seeds as well as whole soy. 

Flax and sesame seeds have anticancer, breast tumor-reducing effects. Both lignans are metabolized to estrogen-like enterodiol and enterolactone, and reduce cell proliferation and apoptosis.[xiv] While each works a bit differently, both may be useful as an effective adjuvant therapeutic agent against tumor development and progression, and therefore, could be used in the prevention and/or treatment of various types of cancer. Studies show that higher intakes of lignans such as flax and sesame seeds are associated with a reduced risk of breast cancer. Flax seed works with tamoxifen to inhibit breast cancer tumor growth, so if you choose to take tamoxifen, know that you can also benefit from flax.  

I have written extensively on the benefits of flax seed, but to recap, a few of the benefits of flax are the following:

  • Decreases cell proliferation rates and inhibits tumor growth in ER+ cancers
  • Decreases angiogenesis (blood supply for tumors) and increases apoptosis (cancer cell death)
  • Influences ER-negative and ER-positive tumors by decreasing insulin-like growth factor-1 (IGF-1), epidermal growth factor receptor (EGFR), HER2 and the vascular endothelial growth factor (VEGF) which supports angiogenesis
  • Reduces growth and metastasis of ER-negative and triple negative breast cancers
  • Favorably influences tumor suppressor genes

For more on flax seed and breast cancer, please read some of my other posts, such as  Demystifying Flaxseed and Estrogen and Flaxseed, Better Than Tamoxifen for Breast Cancer.

Soy: Numerous studies indicate that genistein, the most abundant isoflavone present in soybeans, has anti-proliferative effects on various cancer cells, including prostate, ovarian, and breast. Like other phytoestrogens, genistein interferes with the effects of estradiol by binding to estrogen receptors. This is good as soy may also inhibit inflammation and boost anticancer immune responses, while other estrogens do not. The following are a few key findings of soy[v]:

  • Inhibits NF-kB activity in prostate, breast, lung, and pancreatic cancer cells. Nf-kB plays a crucial role in immune response, inflammation, cell growth and survival.
  • Selective tyrosine kinase inhibitor impeding angiogenesis, a major factor in cancer growth and proliferation. Tyrosine kinases play important roles in cell proliferation, survival, migration and differentiation are often altered in cancer cells, leading to malignancy
  • Induces cancer cell death (apoptosis) in several cancer cell lines, including prostate, ovarian, and breast cancer
  • Modulates EGF (epidermal growth factor) which has been implicated in the development and growth of many types of cancer cells
  • Long-term consumption seems to result in a decreased response to stimulation by estradiol[vi]

Please note that soy consumption is somewhat controversial. Please work with your coach or medical professional to see if soy consumption is right for you.

More Notable Phytoestrogens                                                                            parsley root

  • Apigenin is a natural flavonoid commonly found in fruits and vegetables such as parsley, celery, thyme, chamomile tea, and oranges. The chemical structure of apigenin is similar to estrogen and as such it mimics estrogen. 2107 research indicates that phytoestrogens such as apigenin and resveratrol have the therapeutic potential act like SERMs and could be considered in the development of therapeutics for breast cancer and brain disease.[vii] Extensive studies show that apigenin has potent antioxidant and anticancer activities in ER-positive and ER-negative breast cancer. Apigenin also inhibits proteasome, which certain cancer cells need for survival. By inhibiting proteasome, phytoestrogens such as apigenin induce apoptosis in prostate, breast, and many other cancer cell lines.[viii]
  • Pau d’ Arco exhibits selective anti-proliferative effects in carcinoma cell lines. A study performed at the Strang Cancer Prevention Center in New York found that the anti-proliferative effects of herbal medicines such as pau d’arco may correlate with down-regulated estrogen responsive genes and up-regulated apoptosis-specific genes. The researchers believe their data validates the need to prioritize efficacious herbal medicines and concluded that phytoestrogens such as pau d’arco may provide an alternative or complementary approach to endocrine therapy for breast cancer.[ix] Read more
  • Broccoli: The sulforaphane in broccoli (particularly in broccoli seeds and sprouts) has been found to inhibit proliferation and down-regulates hormone receptor expression in MCF-7 cells. Sulforaphane also passes the blood brain barrier and targets cancer stem cells. If you cannot find sprouts locally, I recommend a supplement.sprouts
  • Luteolin and Naringenin: Flavonoids, especially flavones such as luteolin and flavanones such as naringenin are potent aromatase inhibitors. [x] Luteolin has also been found to down-regulate aromatase gene expression. Luteolin is found in celery, thyme and chamomile tea. Some rich sources of naringenin include bergamot, grapefruit, tomatoes, and tart cherries.
  • Quercetin, found in abundance in food sources such as apples, onions, tea, and red wine, has been reported to have strong antioxidant, anti-inflammatory, antiviral, and anticancer effects. It has the ability bind at high affinity to estrogen receptors, resulting in inhibition of estrogen-regulated cell growth and proliferation[xi]
  • Hesperetin, found in citrus fruits and essentials oils, exerts it anticancer actions by inhibiting cell proliferation, inducing apoptosis, and by regulating aromatase activity and oxidative stress. Although hesperetin is unable to bind to ERs, it is effective in inhibiting cell proliferation of ER+ breast cancer and dramatically decreasing tumor size and other actions. Hesperetin has also been found to reduce serum estrogen levels and down-regulate estrogen target genes and estrogen metabolism-related genes.[xii]. Try putting a drop or two of lemon essential oil in your water, or grating the peel of an organic lemon.
  • Black seed contains thymoquinone, a phytochemical compound found in plant Nigella sativa. It has been found to initiate apoptosis, improve estrogen metabolism, and regulate signally pathways in breast cancer.
  • Vitamin E inhibits cell proliferation, down-regulates the expression of ERα, ERβ, COX-2, and serum estrogen levels (should always be mixed tocopherols, not just d-alpha.
  • Red Clover binds to estrogen receptors, inhibits cell proliferation, and initiates apoptosis in ER+ breast cancer cells.
  • Ellagic acid, a dietary flavonoid present in berries, grapes, pomegranates, and nuts, inhibits cell proliferation and promotes apoptosis in ER+ breast cancer cells.
  • Eugenol, a compound found in clove oil, inhibits cell proliferation and initiates cancer cell death in both ER+ and ER- breast cancers. Excitingly, one study done in Indonesia found that eugenol  is a potent ERa antagonist. The researchers indicate that not only does it work just like tamoxifen, but it may actually work even better.
  • This list is  not inclusive: There are many more powerful phytoestrogens. For more cancer-fighting alternatives to pharmaceuticals, please read my articles on Natural Alternatives to Aromatase Inhibitors and Natural Alternatives to Tamoxifen.

Phytoestrogens can be our friends, but know that herbs are powerful. I have no concerns with food-based phytos, but do take care with extracts. They are best rotated so as to maximize benefits, reduce the chances of resistance, and avoid interactions. Drugs, of course, are often even more dangerous, yet are routinely prescribed.

                               Trust me, I’m a doctor” Peter Gøtsche

I interviewed Peter Gøtsche, author of Deadly Medicines and Organised Crime, on my radio show a few years back. Amazing man, whose controversial views have since gotten him tossed from the Cochrane Collaboration, which he co-founded. Sadly, there are many who wish to silence the voices who speak against Big Pharma.

Like me, Gøtsche worries that most people let their doctors make the decisions for them, but the evidence tells us that we should be cautious. He is a strong advocate for the avoidance of drugs and while not against medical interventions, believes one can not just blindly follow the orders of the medical community.

Notably, there is tremendous variability in the metabolic processing of phytoestrogens and pharmacological drugs, thus establishing the difficulty and complexity of this topic. The bottom line is that it extremely important that one understand that it may not make logical sense to attempt to poison one’s way back to health. Certainly drug therapies have worked for many. That said, NO ONE was every born tamoxifen or AI deficient, but over time we may become estrogen dominant, increasing our risk for cancer. It behooves us all to do our research and decide for ourselves whether drugs or holistic remedies are best, or even a combination of both.  

Estrogen plays many important roles in humans, so it may not make sense to arbitrarily take it away. If you are estrogen dominant (meaning out of balance with progesterone), you may want to consider a bio-identical progesterone cream (I like that one as it is paraben-free, soy-free, and Non GMO).

Read Part I of this article HERE.

Reminder: To get an additional $30 off on the online course for breast cancer,  Toxic Free Me, enroll now and use this LINK. This course will further delve into alternatives for anti-hormonal therapies.

An online course not right for you? Know that I am always there for individual consultations.  To inquire about a consult, please visit me HERE.

Life is a journey, just be sure that journey is on-course for a healthy life.

In your everlasting good health,


~~If you don’t know your options, you don’t have any~~

ej portrait 150res for PrueElyn Jacobs is a breast cancer survivor and holistic cancer strategist who helps people make healthier, less-toxic choices for their healing. She emphasizes the importance of not just surviving cancer, but surviving well and reducing the risk of recurrence. She is a Contributing Editor for The Truth About Cancer and is on the Medical Advisory Board for BeatCancer.Org and the Advisory Board to the Radical Remission Project. Elyn has written for numerous journals and publications. She was the former Executive Director of the Emerald Heart Cancer Foundation and the creator and host of the Survive and Live Well Radio Show. To contact Elyn, visit www.elynjacobs.com. Elyn offers consults via Skype, phone, or in-person. Elyn does not provide online advice.

Elyn Jacobs does not provide medical advice. The information provided is for general information only. No online site should be used as a substitute for personal medical attention.

This information is for educational purposes only and is not a recommendation to forgo medical advice and treatment.  This post is not intended to treat, cure, prevent, or diagnose any disease or condition. This post does not represent medical advice nor should it be considered to be medical advice or a replacement for medical advice.  I encourage you to discuss this information with your integrative oncologist, naturopathic doctor, or conventional oncologist. The information provided is from my research and not to be taken as scientific evidence.

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[i] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535874/; Notably, there are numerous  crsos-references cited in this article that support the use of phytoestogens as nutraceutical anti-hormone therapies for various cancers.

[ii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535874/

[iii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535874/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4699002/

[iv] https://www.ncbi.nlm.nih.gov/pubmed/27194038; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535874

[v] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535874/#B61-ijms-18-01381; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535874/

[vi] https://www.ncbi.nlm.nih.gov/pubmed/8625449

[vii] https://www.ncbi.nlm.nih.gov/pubmed/28396216; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5033666/

[viii] https://www.ncbi.nlm.nih.gov/pubmed/26771497; https://www.ncbi.nlm.nih.gov/pubmed/25408199

[ix] https://www.ncbi.nlm.nih.gov/pubmed/19578798

[x] https://www.ncbi.nlm.nih.gov/pubmed/21741436

[xi] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203161/#b9

[xii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535874

[xiii] https://www.ncbi.nlm.nih.gov/pubmed/26614455

[xiv] https://elynjacobs.com/2016/02/28/flaxseed-better-than-tamoxifen-for-breast-cancer/; https://www.ncbi.nlm.nih.gov/pubmed/29032105; https://www.ncbi.nlm.nih.gov/pubmed/22136581


Why Aromatase Inhibitors Fail Women

In Alternative Cancer Therapies, Alternatives to Anti-Hormone Therapy For Breast Cancer, Alternatives to Hormone Therapy for Breast Cancer, Alternatives to Tamoxifen, Breast Cancer, Tamoxifen, Uncategorized on November 13, 2017 at 5:27 am

Aromatase inhibitors fail when tumors outsmart them.  Researchers have long been studying how resistance to aromatase inhibitors (AIs) happens so that they can find a solution. The resistance effectively makes these drugs powerless, causing the cancer to return. One in every four or five women relapse within ten years of AI treatment and develop metastatic cancer. [i]

Estrogen plays an important role in the development of hormone-dependent breast carcinomas, or at least some estrogens do. While ovarian estrogen synthesis ceases at menopause, peripheral and local tissue’s aromatization of androgens to estrogens continues and becomes the main source of estradiol (the more cancer-promoting estrogen). What this means is that while your ovaries are no longer producing estrogen after menopause, and your adrenals are producing only a small amount, breast cancer cells may actually have a way to produce their own food supply.

Theoretically, the aromatase inhibitor could be reducing circulating estrogen to dangerously low levels, while estrogen in the breast, axillary, and belly could still be dangerously high. Hence, AIs fail the patient, who then suffers the ill-effects of the drugs with no benefit.

The Research

Until recently, scientists assumed the tumors developed resistance in some way, but didn’t know how. Scientists have now discovered why AIs may stop working in some patients. Research done at the Imperial College London and the European Institute of Oncology in Milan has found that some breast tumors evolve to make their own estrogen, rendering AIs ineffective. While the ovaries cease to produce estrogen after menopause, the hormone is still made in other tissues via the enzyme aromatase.[ii] The team, led by Dr Luca Magnani, found that in one in four patients taking AIs, the tumors had increased production of aromatase in the cancer cells. They found that the tumors were able to increase the number of aromatase genes via a process known as amplification.

So, while AIs work by cutting off the tumor’s fuel supply (estrogen), the cancer adapts by making its own –an efficient survival mechanism. The research points to a particular gene (CYP19A1).  When more copies of this gene are produced, it triggers the increased production of aromatase, the very enzyme the drugs are trying to block. This allows cancer cells to make their own estrogen and thus reproduce and spread.[iii] It seems to be a bit of a survival mechanism-the AI cuts off the food supply so the tumor outsmarts it by making its own.

We found that 21.5% of AI-treated, relapsed patients had acquired CYP19A1 (encoding aromatase) amplification (CYP19A1amp)…CYP19A1 amplification caused increased aromatase activity and estrogen-independent ERα binding to target genes, resulting in CYP19A1amp cells showing decreased sensitivity to AI treatment. These data suggest that AI treatment itself selects for acquired CYP19A1amp and promotes local autocrine estrogen signaling in AI-resistant metastatic patients.[iv]

When an aromatase inhibitor stops working, most oncologists will try another type of AI.  The problem is that if the cancer cells have started making their own aromatase, the second (or third) drug will be useless. Identifying the over-expression of the CYP19A1 may help doctors determine which women are not good candidates for AI therapy or who might be candidates for alternative therapies. The aforementioned researchers are now working on a test to identify whether a patient’s tumor has started to increase aromatase production, and make its own estrogen.

Dr. Magnani also suggested that when cancer returns, a biopsy should be done to see how the cancer has evolved, which may help guide treatment decisions. Often this can be helpful, but just as often, it fails to offer much information. This is a decision you need to make in consultation with your oncologist or other qualified professional.

Obesity Plays a Role

Excess body weight has been linked to an increased risk of postmenopausal breast cancer, and research also suggests that obesity is associated with poor prognosis in women diagnosed with early-stage breast cancer. Fat tissue contains the enzyme aromatase that converts hormones called androgens to estrogens. Human abdominal, breast, and axillary fat have the ability to convert androgens into estrogens.

So, heavier women end up with higher blood estrogen levels as well as enhanced local production of estrogen than leaner women. Elevated serum estrogen levels as well as enhanced local production of estrogen have been considered primary mediators of how increased body weight promotes breast cancer development in postmenopausal women.

On the Horizon

I have long been pointing out that most of have seriously declining levels of estrogen as we age –which has been found to compromise overall health. For this reason, AIs are quite dangerous as they block essential estrogen.

However, it has recently been reported that plasma estrogen levels do not necessarily reflect tissue estrogen concentrations. Several studies have found that tissue estrogen levels may be ten- to 20-fold higher compared to plasma levels in postmenopausal women. Furthermore, recent studies have demonstrated that a large proportion (close to 100%) of the biologically active estrogen is considered to be produced locally in the breast carcinoma after menopause.[v] Therefore, likely a more effective method would be to inhibit estrogen of breast tissue than that of systemic circulation. More studies need to be done on this.

At this point, studies are being conducted in China to see if a locally-applied aromatase-inhibiting patch using letrozole would be effective and offer a less toxic solution to the standard drug AIs.

As reported in AAPS PharmSCiTech (a Journal of the American Association of Pharmaceutical Scientists), a mouse study revealed that compared with oral administration, transdermal administration could produce high local drug concentrations and low circulating drug concentrations. This could reduce systemic side effects. Therefore, it might be a new option for breast cancer therapy to inhibit aromatase activity via transdermal patches for site-specific delivery of letrozole.

But again, more studies need to be done to determine if a local patch would be effective for cells outside the breast area, and independent studies should also be done (ones not paid for by a pharmaceutical company).

So, should women with estrogen receptor-positive breast cancer take inhibitors of estrogens? The decision of whether or not to use estrogen blockers is a complex one that each woman can only make if fully informed. The potential negative effects on the brain, heart, and overall quality and quantity of life, as well as treatment failure, should be weighed against the immediate risk of recurrence.

However, in making a treatment decision, it is most important to speak with an oncologist who is fully aware of the limitations and potential negative effects of these drugs and who is prepared to discuss alternative options. It is equally important to educate yourself on natural alternatives as typically these options are not discussed by medical doctors.

Important is to realize that in the presence of adequate progesterone, estrogen cannot easily fuel breast cancer tumors.[vi] Perhaps for now, a better solution is to make every effort to reduce aromatase activity and to increase production of progesterone.

Progesterone may also be the answer to why AIs seem to work for some.  I could postulate that the answer again might be progesterone, especially for those patients who are PR + as well as ER+, but that is just one possibility.

For more information regarding consideration of natural alternatives, please read:

Natural Alternatives to Hormone Therapy for Breast Cancer  

Why You May Want to Reconsider Estrogen-Blocking Aromatase Inhibitors and Tamoxifen 

* The CYP19A1 gene provides instructions for making an enzyme called aromatase. This enzyme converts a class of hormones called androgens, which are involved in male sexual development, to different forms of the female sex hormone estrogen. Mutations in this gene can result in either increased or decreased aromatase activity.

This information is for educational purposes only and is not a recommendation to forgo anti-hormone therapy. It is not intended to treat, cure, prevent, or diagnose any disease or condition. This post does not represent medical advice nor should it be considered to be medical advice or a replacement for medical advice.  I encourage you to discuss this information with your integrative oncologist, naturopathic doctor, or conventional oncologist and make your own decisions.  The information provided is from my research and not to be taken as scientific evidence. 

ej portrait 150resElyn

~~If you don’t know your options, you don’t have any~~

Elyn Jacobs is a breast cancer survivor and certified holistic cancer strategist who helps people make better, healthier, non-toxic choices. She emphasizes the critical nature of addressing the root cause of cancer and not just its presenting symptoms (such as the tumor). Elyn specializes in understanding the role of estrogen in breast cancer and debunks the myths associated. She is a Contributing Editor for The Truth About Cancer and was creator and host of the Survive and Live Well Radio Show on the Cancer Support Network. Elyn is on the Medical Advisory Board for BeatCancer.Org and is on the Advisory Board to the Radical Remission Project. Elyn was the former Executive Director of the Emerald Heart Cancer Foundation. Contact Elyn via her website. Elyn offers consults via Skype, phone or in person.

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[i] https://www.nature.com/articles/ng.3773   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5326683/



[iii] https://www.ncbi.nlm.nih.gov/pubmedhealth/behindtheheadlines/news/2017-01-24-new-insights-into-why-breast-cancer-drugs-fail-for-some-women/

[iv] https://www.nature.com/articles/ng.3773

[v] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2974128/

[vi]  http://ajcn.nutrition.org/content/45/1/277.short