The current oncological recommendations for anti-hormone therapy (endocrine therapy) for postmenopausal women with early-stage breast cancer vary. Some oncologists recommend aromatase inhibitors for five years, with tamoxifen to follow and some the reverse, and some just one or the other. However, the recommendations rarely take into consideration risk of prior cardiovascular disease history, cardiovascular disease risk, or overall risk of death when choosing between the different therapeutic options. (For premenopausal women, the standard is usually tamoxifen, with little attention to risk factors for blood clots, stroke, and endometrial cancer.)  Importantly, while both therapies can prolong disease-free survival, they don’t necessarily increase overall survival.

In the discussion of adjuvant endocrine therapy, doctors downplay the fact that aromatase inhibitors (AIs) are associated with musculoskeletal symptoms, heart damage, osteoporosis, and increased risk of bone fracture. Estrogen protects against heart disease, and consistent research has suggested that the suppression of estrogen raises the risk of cardiovascular disease, among other life-challenging issues. AI treatment reduces nearly all circulating estrogen. Estrogen is essential to the health of all parts of your body, from your eyes to your heart to your brain to everywhere else.

Many doctors also fail to stress that tamoxifen is associated with an increased risk of uterine cancer, stroke, deep venous thrombosis (blood clots), and severe muscle pain. They also fail to inform their patients that while both therapies can prolong disease-free survival, they rarely increase overall survival—especially in the case of aromatase inhibitors. All this at a tremendous cost to quality of life.

Tamoxifen and aromatase inhibitors have distinct toxicity profiles. However, individual studies have not shown a significant difference in overall toxicity between patients treated with these therapies. The lack of association between disease-free survival and overall survival prompted a 2011 meta-analysis published in the Journal of the National Cancer Institute. The study evaluated the toxicities of the two endocrine therapy options.

The Research:

The meta-analysis confirmed that an aromatase inhibitor (AI) may not the best therapy for all postmenopausal women with hormone-receptor positive, early-stage, breast cancer. The authors conducted the study to clarify why AIs, when compared with tamoxifen, increased disease-free survival but not overall survival. AI toxicities were suspected to counteract decreased recurrence rates.[i] However, as presented in the analysis, tamoxifen wasn’t necessarily safer than AIs, so the authors concluded that switching from tamoxifen to AIs would  balance the efficacy and toxicity of these treatments. What this means to you is that they are recommending that you ‘switch’ from one drug to another after a few years to reduce toxicity–but that also means you suffer the consequences of both drugs.

The authors noted that although several large randomized trials have examined the benefit of the aromatase inhibitors anastrozole, letrozole, and exemestane — as compared with 5 years of tamoxifen — the trials have failed to demonstrate a statistically significant improvement in overall survival.

The Methods:

Relevant trials were identified through a search of the MEDLINE and EMBASE databases, a search of the American Society of Oncology Annual Meetings from 2000 through 2009, and a search of the San Antonio Breast Cancer Symposium Annual Meetings from 2000 through 2009. 377 relevant articles were identified, of which 7 randomized controlled phase-3 trials with 30,023 patients met inclusion criteria.

The analysis considered six adverse events: cardiovascular disease, cerebrovascular disease, venous thrombosis (DVT), bone fracture, endometrial cancer, and other secondary cancers.

The Highlights: (Noting that longer duration of one therapy implies a shorter duration of the other)

• Longer duration of AI use was associated with higher odds of developing cardiovascular disease.
• Longer duration of AIs was associated with a 66% reduction in the odds of developing endometrial cancer compared with tamoxifen use.
• Both AIs and tamoxifen increase the risk of other second cancers, but switching from tamoxifen to aromatase inhibitors may decrease the odds of second cancers.
• Longer durations of aromatase inhibitor use were associated with decreased odds of venous thrombosis compared with tamoxifen.
• Longer durations of AIs were associated with increased odds of bone fractures compared with tamoxifen.
• Longer durations of AI use was associated with a statistically significant increase in the risk of raised cholesterol (hypercholesterolemia. Shorter durations of AIs might reduce the odds of high cholesterol.
• The relative harm of 2 to 3 years of tamoxifen was not reduced by switching to aromatase inhibitors.
• Compared with those treated with 5 years of either tamoxifen or aromatase inhibitors, those treated with a switching strategy had a statistically lower risk of death without breast cancer recurrence.
• A retrospective cohort study of women diagnosed with breast cancer at age 66 or older between 1992 and 2000 found that more patients died of cardiovascular disease than of breast cancer.[ii] The researchers recommended that the age of the patient be taken into consideration when choosing between endocrine therapies (or in this author’s opinion, instead offering holistic alternatives).

While the study was performed to compare the two conventional treatment options, sadly they did not simultaneously compare the effectiveness of natural alternatives. Again, use of aromatase inhibitors vs tamoxifen is associated with increased risk for cardiovascular disease, cholesterol, severe muscle and joint aches, and bone fractures. Use of tamoxifen vs aromatase inhibitors is associated with increased risk for venous thrombosis, stroke, and endometrial cancer. Clearly both of these toxic therapies cause harm, often more harm than good — even if one does switch from one therapy to the other.

Other Reasons for Opting Out in Favor of Natural Alternatives:

• A study published in the Journal of Clinical Oncology, 2016, reported that women in their 40’s with chemotherapy-induced amenorrhea should avoid aromatase inhibitors. Many women who have ceased menstruating post-chemo later recover ovarian function. What the researchers found was that ovarian estrogen production will decrease the effectiveness of AI therapy and that the therapy could actually stimulate ovarian production of estrogen. Unfortunately, the researchers concluded that the way to prevent this would be to shut down ovarian function as well as to offer tamoxifen.  [iii]
• A study reported at the San Antonio Breast Cancer Symposium in 2106 reported that endothelial dysfunction, a predictor of cardiac disease, is a significant side effect of AI therapy among postmenopausal women, posing the problem again — that while the therapy may inhibit recurrence, it does not improve overall survival time.[iv] Estradiol appears to be important for regulating healthy endothelial function.
• Endogenous estrogen (the estrogen your body produces) is neuroprotective. The breadth of literature on the role of estrogen in cognitive function is vast. Many women will attest to the fact that peak cognitive function corresponds with cyclic changes in circulating estrogen during their menstrual cycle.
• Estrogen has also been found to suppress the inflammatory processes that contribute to neurodegeneration as well as to improve stroke outcome.[v] It is well documented that women are ‘protected’ against stroke until menopause, when estrogen levels decline.
• Numerous studies have shown that beyond the aforementioned complications, tamoxifen can increase the risk of developing liver cancer and raises overall inflammation of the body, a known precursor to cancer.
• A study reported at the San Antonino Breast Cancer Symposium 2016 looked at endothelial dysfunction, a predictor of cardiac disease.  Interestingly, they determined that the vast majority of participants who had increased cardiac risk after taking AI therapy would not have been considered at risk pre-treatment. The study indicated that the cancer benefit may not be worth the cardiac risk, both for younger and older patients.
• Also reported at the 2016 Symposium was that AIs, associated with reductions in endothelial function, could contribute to cardiovascular disease independent of the duration of therapy.

With a growing number of cancer survivors, it is very important that we look to understand the long-term complications of conventional cancer treatment. Most postmenopausal women with early-stage breast cancer are at greater risk of dying from cardiovascular disease than their breast cancer. Further, they are at greater risk of a significant reduction in quality and quantity of life from the other overwhelming effects of conventional treatments in general.  Even worse, most doctors don’t even bother to run hormone level tests–they simply prescribe the harmful drugs. Clearly, the current toxic anti-hormonal therapies cause harm, often more harm than good. The question to be asked is ‘is it worth it?”

But, my doctor says they work:

Research published in 2106 in the Journal of Clinical Oncology analyzed the information collected for the BIG 1-98 study that was designed to see whether AIs or tamoxifen was most effective. The study was rather useless—all it managed to say was that the treatments were so toxic that most women were either non-compliant or discontinued treatment due to the side effects. Sure can’t blame them. Again, while these treatments can prolong disease-free survival, they do not always prolong overall survival. This study made no mention of those who died without recurrence (meaning from treatment-induced effects). [vi] It also made no mention of safer alternatives, and likely instilled more unnecessary fear-based compliance out of those who read the study.

If your reason for reading this article was your desire for natural alternatives to anti-hormone therapy, please read: Natural Alternatives to Hormone Therapy for Breast Cancer.

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. 

Elyn

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

Elyn Jacobs is a breast cancer survivor and 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.medscape.com/viewarticle/756567

[ii] https://www.ncbi.nlm.nih.gov/pubmed/21689398?dopt=Abstract&holding=f1000,f1000m,isrctn ; https://www.ncbi.nlm.nih.gov/pubmed/16944964

[iii] http://ascopubs.org/doi/abs/10.1200/JCO.2015.62.2985?rss=1

[iv] http://www.pnas.org/content/108/47/18879

[v] https://www.ncbi.nlm.nih.gov/pubmed/9445346

http://www.pnas.org/content/108/47/18879.full.pdf

[vi] http://ascopubs.org/doi/abs/10.1200/JCO.2015.63.8619

http://www.mdedge.com/oncologypractice/article/119926/breast-cancer/aromatase-inhibitor-effect-endothelial-function-may