And this drug does WHAT?
- Deb Dekoff
- Mar 31, 2017
- 10 min read
From diagnoses and all through treatment, we bow and kowtow to the medical professionals around us. After all, they've gone to school, graduated at the top of their prospective classes, entered a field in which math and science dominate, focused on a particular field of study, did fellowships and internships, and really know their stuff. We put our full faith and trust in them. Unequivocally. End-all experts. They tell us: don't believe everything you hear from others, aka peer reviews of those who are in the same cancer ship, and avoid websites except for likes of American Cancer Society and Susan Komen.
In preparation for my upcoming oncology visit where adjuvant therapy in the form of an estrogen blocker is the primary focus, I've done some research. You see, as an educator, I question. A LOT.
Why should I take this drug? What will it do? How does it work? What do studies show?
Great. Things on the surface sound fine:
The drug is an estrogen inhibitor. Your cancer feeds on estrogen, so if we inhibit estrogen, it should aid in keeping the cancer from coming back. Studies show that if you take this drug for five years...yet some people stay on this drug for as long as ten...research doesn't show much of a discernible difference in relapse rates between years...
Why do you feel an AI is better for me? Patients who have ER-positive tumours with unfavourable characteristics, such as HER-2 positivity, PgR negativity or nodal positivity, are likely to be selected for immediate AI therapy. However, patients with ER-positive tumours without unfavourable characteristics are likely to be selected for tamoxifen treatment for 2–3 years before taking an AI for 2–3 years. (1)
Sounds about right. And many patients would hold out their hands and say, "Okay, let me fill this prescription."
But...
What about side effects?
(Sandwich style response goes here.)
SOME people report no side effects. Others have experienced...FILL IN THE BLANK. However, EACH PATIENT IS DIFFERENT (there's that line again), and you may not experience any side effect.
And out the door a regular, doctor abiding patient goes.
But, I'm done with accepting prescriptions for my health at face value. When first diagnosed with cancer one experiences SHOCK. (How can this happen to me? I eat right, I exercise, I avoid toxins in food and in life in general. Heck, I even avoid toxic people!) We jump at the first open surgery date, and rightfully so. Still numb from shock and surgery, we enter chemo. And as the poison enters our system it negatively effects our cognition. (Clarity is lacking - I was walking in a cloud, concerned that I had early onset Alzheimers. ) A brief period of healing is permitted before radiation, where we are burned, scorched, and for the second time, see the outward bodily effects of having cancer. We are still too chemically addled, and physically and emotionally fried. We place one foot in front of the other and are led to the next step in this cancer treatment maze: an estrogen blocking pill.
And this is where I stop. I am stomping my feet.
The drug, I was told was "right" for me is Anastrozole.
Data. I want data. PEER review data - as my starting point. Women I know and trust to tell the truth. MEDICAL research data - studies
DATA from the pharmaceutical company
I want to know, NEED to know, every negative nuance of a drug that I might be given. And, I am exploring other options, such as those provided by nature: food sources.
We are our own best advocates. The decision to take a drug or not, to choose one over the other, is ultimately ours.
This drug does WHAT?
Aromotase Inhibitor:Anastrozole
Common side effects Blurred vision - chest pain or discomfort - dizziness - headache - nervousness - pounding in the ears - shortness of breath slow or fast heartbeat - swelling of the feet or lower legs - Acid or sour stomach -back pain -belching -body aches or pain -bone pain -congestion -constipation -decrease in height -diarrhea -dry mouth -dryness or soreness of the throat -feeling of warmth -fever -flushing or redness of the skin, especially on the face and neck -heartburn -hot flashes -increased appetite -indigestion -lack or loss of strength -loss of appetite -mood or mental changes -pain in the back, ribs, arms, or legs pain, -general-pelvic pain -runny nose- skin rash -stomach discomfort, upset, or pain -tender, swollen glands in the neck -trouble in swallowing -voice changes -vomiting -weakness -weight loss (5)
(I did not list the "less common" side effects.)
JOINT AND MUSCLE PAIN - (Did you note how many times the above list mentioned pain?)
Peer reviews: I have not yet spoken to one woman who was place on an AI (Aromotase Inhibitor) (Anastrazole) who did not experience debilitating bone and joint pain. Not one. In fact, I even spoke to a male competitive body builder who has used this drug - and he said, "Yeah, everything hurts. Bad. But I do it for competition purposes only." He doesn't have to stay on it for five years, or seven, or ten.
The incidence of arthralgias and myalgias appear to be about two-thirds higher with an AI than with tamoxifen. (1) (Arth -bone, myal - muscle And "incidence" means the reporting of pain. ) In studies of AI-related joint symptoms, anywhere from 20-50% of women on therapy reported the side effect. (9)
Some studies have shown that having received prior chemotherapy, prior hormone replacement therapy, prior taxane chemotherapy (paclitaxel, taxotere) and having had their last menstrual period within 5 years may predict increased risk. (9) Great. Count me in that group!
AI-related joint symptoms can cause significant pain and interfere with functioning and quality of life. (9)
HEART ATTACK Increase in ischaemic cardiovascular events (arteries are narrowed, less blood and oxygen reaches the heart muscle. This is also called coronary artery disease and coronary heart disease. This can ultimately lead to heart attack. Ischemia often causes chest pain or discomfort known as angina pectoris.)
It might be due to estrogen depletion in the coronary arteries leading to loss of the vasodilatory response of estrogen to stress Alternatively, the observation might stem from a small cardio-protective benefit from tamoxifen rather than a deleterious effect of AIs. (1)
BONE FRACTURES: ARIMIDEX can cause bone softening/weakening (osteoporosis) increasing the chance of fractures. In a clinical study in early breast cancer, there were more fractures (including fractures of the spine, hip, and wrist) with ARIMIDEX (10%) than with tamoxifen (7%) (6)
Other noted REACTIONS
Some patients taking ARIMIDEX had an increase in cholesterol. Skin reactions, allergic reactions, and changes in blood tests of liver function have also been reported.
Manufacturers' Website: Most common side effects seen with ARIMIDEX include hot flashes, joint symptoms (including arthritis and arthralgia), weakness, mood changes, pain, back pain, sore throat, nausea and vomiting, rash, depression, high blood pressure, osteoporosis, fractures, swelling of arms/legs, insomnia, and headache. (6) In advanced breast cancer trials, the most common side effects seen with ARIMIDEX versus tamoxifen include hot flashes, nausea, decreased energy and weakness, pain, back pain, headache, bone pain, increased cough, shortness of breath, sore throat, and swelling of arms and legs. Joint pain/stiffness has been reported in association with the use of ARIMIDEX (6)
So, what are doctors and drug companies suggesting to lessen this?
Take two aspirin... We are given more drugs. And told to stay the course. The euphemistic phrase: "The management of joint symptoms is of utmost importance to helping patients complete their prescribed therapy in full" is telling. (9) So is advice to take "pain relevers" .
This drug does WHAT?
Aromotase Inhibitor: Letrozole
Common Side effects: Decreases bone density - increases bone fractures and osteoporosis - hot flushes - nausea - hair thinning - fatigue - dizziness -drowsiness -decreases in white blood cell counts- joint pain - nausea, weight decrease- vaginal irritation -pain in the extremities.
Other important less commonly reported side effects: blood clots, other cancers, stroke, heart attack and endometrial cancer.
PEER REVIEWS: None
HAIR THINNING Great. IT's bad enough our hair is finally growing back after chemo.
FRACTURES, DECREASED BONE DENSITY As we grow older, our bone density decreases. Certain drugs, such as synthroid, leach the bones as well. And when we look at the elderly, we know some of them never recover from a fall in which bones were broken.
Research on Letrozole seems a bit more sparse in comparison to Arimidex, yet the info I've found state that women have fewer reported side effects.
REPORTED is the operative word here. Some women may not be reporting the side effects to their doctor, and the doctor may not be reporting to the FDA.
In a patient-preference study, those receiving letrozole reported fewer adverse events than those receiving anastrozole (43% vs 65%; P < 0.003), and more patients preferred letrozole to anastrozole (68% vs 32%; P < 0.01). (2)
Anastrozole vs Letrozole Letrozole is generally well tolerated and has a similar tolerability profile to tamoxifen; the most common treatment-related adverse events were hot flushes, nausea and hair thinning. In patients with tumours that had progressed on antiestrogen therapy, letrozole was tolerated as least as well as, or better than, anastrozole (3)
And it is less costly: The efficacy, cost effectiveness and favourable tolerability profile of letrozole are reflected in current treatment guidelines recommending the drug as first-line therapy for advanced breast cancer. Letrozole is superior to tamoxifen for first-line treatment and is at least as effective as standard second-line treatments in disease that has progressed on antiestrogen therapy. For early-stage disease, letrozole is superior to tamoxifen in the neoadjuvant setting, and prolongs disease-free survival when administered after the standard 5-year period of adjuvant tamoxifen therapy. (3)
in-direct comparisons suggest stronger evidence for the use of letrozole compared with other AIs for breast cancer in postmenopausal women who require estrogen-deprivation therapy. (2)
From the manufacturer: The most serious side effects seen with Femara are bone effects (fractures, decreased bone density and osteoporosis) and increases in cholesterol.
And this caveat, according to the drug manufacturer: Until you know how it affects you, use caution before driving or operating machinery. (10)
Comparison of AIs to Tamoxifen Compared with tamoxifen, anastrozole and letrozole significantly improved disease-free survival as early adjuvant treatment for hormone-receptor-positive disease. Switching to anastrozole or exemestane after 2 to 3 years of adjuvant tamoxifen for a total of 5 years of therapy was also more effective than continued tamoxifen.
This drug does WHAT?
Tamoxifen: blood clots - cataracts - high cholesterol - stroke - uterine cancer - swelling of the fingers, hands, feet, or lower legs - feeling of warmth - swelling of the extremities: hands, feet, legs - weight gain or loss -troubled breathing at rest -skin changes -noisy, rattling breathing
Tamoxifen was approved by the FDA within ONE MONTH of a study. The results sound remarkable: taking tamoxifen for 5 years post diagnosis reduces a woman’s risk of estrogen receptor (ER)-positive breast cancer recurrence by about 50%. But wait, as astounding as that seems, what does it really mean? Over the 15 years of the study, those taking tamoxifen for five years had a 15 percent chance of dying from breast cancer. Those who took tamoxifen for a decade had a 12.2 percent chance of dying from this disease. That’s significant (an absolute risk reduction of dying of 2.8%) but doesn’t sound as impressive as a 50 percent relative risk reduction.
The only trouble is that tamoxifen also acts like estrogen on the uterine lining. Instead of blocking estrogen there, it activates the tissue as if it were estrogen. Roughly 3 percent of the women who took tamoxifen for 10 years developed endometrial cancer. That was approximately double the rate of those who only took tamoxifen for five years. So, you sort of rob Peter to pay Paul. You can reduce your risk of breast cancer by 50 percent but you double your risk of endometrial cancer. (12)
PEER review:
All of the BC patients on Tamoxifen have reported "less ability to focus/cognate"; several have reported inability to lose weight. All of have "taken breaks" while on this medication.
BLOOD CLOTS Tamoxifen, for which the risk of deep venous thrombosis and pulmonary embolism is increased approximately twofold (1)
The lack of significant cardiovascular benefit in most randomized trials for tamoxifen may be due to an increase in triglycerides and clot promoting proteins, which offset the beneficial cardiovascular effects of tamoxifen (1)
UTERINE CANCER
Peer review: I met a lady who said, "Get all your lady parts cut out!" Why? Because she wound up with Uterine cancer, presumably from tamoxifen.
CATARACT AND EYE
BLOOD PROBLEMS
High cholesterol levels in the blood—Tamoxifen can increase cholesterol levels.
Weight gain or Loss
BUT...there is one benefit of tamoxifen - it acts like estrogen for bone and reduces the risk of osteoporosis.
The final factoid conclusion ... Aromatase inhibitors (anastrozole, letrozole, exemestane) are associated with significant bone loss in post-menopausal women. (8)
All AI's cause pain with Anastrozole causing more bone and muscle pain then Letrozole. Doctors will prescribe "pain relieving medication" such as aspirin, tylenol; and also increasing calcium (vitamin D) Tamoxifen increases the rate of blood clots and uterine cancer.
As a physically active weight-lifting and running female, I have a lot to consider. As one breast cancer survivor said, "Quality of life became more important to me that the quantity. I couldn't enjoy living in that much pain."
REPORT your side effects to the FDA 1-800-FDA-1088. With knowledge, comes power. Be powerful in your health.
CHART: (11)
Research: Citations
1. Fabian, C. J. "The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer." International Journal of Clinical Practice. December 2007. Accessed March 31, 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228389/. 2. Berry, J. "Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer." Clinical therapeutics. November 2005. Accessed March 31, 2017. https://www.ncbi.nlm.nih.gov/pubmed/16368441.
3. Simpson, D., M. P. Curran, and C. M. Perry. "Letrozole: a review of its use in postmenopausal women with breast cancer." Drugs. Accessed March 31, 2017. https://www.ncbi.nlm.nih.gov/pubmed/15161328.
4. "Anastrozole (By mouth) - National Library of Medicine - PubMed Health." National Center for Biotechnology Information. Accessed March 31, 2017. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0009010/?report=details#side_effects. 5. "Anastrozole (Oral route)." National Center for Biotechnology Information. March 01, 2017. Accessed March 31, 2017. https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0045745/#DDIC600131.side_effects_section.
6. "ARIMIDEX Side Effects." ARIMIDEX Side Effects | ARIMIDEX® (anastrozole) Tablets. Accessed March 31, 2017. https://www.arimidex.com/about/side-effects.html.
7. "Femara® (letrozole) | Products | Novartis Oncology." (letrozole) | Products | Novartis Oncology. Accessed March 31, 2017. https://www.novartisoncology.com/news/product-portfolio/femara.
8. Khachidze, N., E. Giorgadze, and M. Tsagareli. "ADJUVANT (HORMONAL) THERAPY AS A CAUSE OF BONE LOSS IN PATIENTS WITH BREAST CANCER (REVIEW OF LITERATURE)." Georgian medical news. January 2017. Accessed March 31, 2017. https://www.ncbi.nlm.nih.gov/pubmed/28252426.
9. Cancer Resources from OncoLink | Treatment, Research, Coping, Clinical Trials, Prevention. "Aromatase Inhibitor-Related Joint Pain." OncoLink. Accessed March 31, 2017. https://www.oncolink.org/cancers/breast/treatments/hormone-therapy/aromatase-inhibitor-related-joint-pain.
10. "Femara® (letrozole) | Products | Novartis Oncology." (letrozole) | Products | Novartis Oncology. Accessed March 31, 2017. https://www.novartisoncology.com/news/product-portfolio/femara.
11. Hormonal Therapy Side Effects Comparison Chart. (n.d.). Retrieved April 01, 2017, from http://www.breastcancer.org/treatment/hormonal/comp_chart
12. Graedon, T. (2017, January 30). Should Breast Cancer Patients Get Back On Tamoxifen? Retrieved April 01, 2017, from https://www.peoplespharmacy.com/2012/12/06/should-breast-cancer-patients-get-back-on-tamoxifen/
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