WTF!

Any science-minded research-based person is going to want data and research to understand a problem. When it comes to offering women a drug to fight estrogen positive cancer, elementary protocol seems thrown out the window.

How do we begin a science experiment? Have an idea of the question you want answered? Have some variables? Monitor the experiment? But, you'll make sure you have some baseline data perhaps?

Baseline data such as "What are my current hormone levels? Dehydroepiandrosterone (DHEA) Sulfate Estradiol Estrogens (Total), Serum Estrone Testosterone (Free), Serum with Total Testosterone Progesterone ? Especially since the last time they were read, was BEFORE chemo!

Often, NO BASELINE DATA is taken for women who are to go on Arimidex. NONE. Why?

Because the drug takes the estrogen level down as low as it could possibly be SO IT DOESN'T MATTER WHERE YOU START.

Um, what about the other hormonal levels? Nope. Not tested either. I pushed. Why not? Insurance does not pay for it. I said I'd pay for it. "We wouldn't know how to read it. Assays are too low." How do we know it will work on me? Is there a TEST to find efficacy? And what if individualizing this drug?

But baseline data aside, let's talk about the insiduous effects of this drug. My words and interpretations of hours of reaserch are in the green, therefore, if you read the green first, you'll see a flow. The research link is below. And important supportive info directly from the research is in RED.

First, research shows that BMI is definitely related to cancer: http://ascopubs.org/doi/full/10.1200/jco.2012.42.0273?utm_medium=cpc&utm_campaign=J_Clin_Oncol_TrendMD_0&utm_source=TrendMD

The suppressed levels of plasma estradiol and estrone sulfate in postmenopausal women with early ER-positive breast cancer treated with the AIs anastrozole and letrozole are related to BMI.

And having that higher BMI equates to higher estrogen in the body: http://ascopubs.org/doi/full/10.1200/JCO.2009.27.4290?utm_medium=cpc&utm_campaign=J_Clin_Oncol_TrendMD_0&utm_source=TrendMD

While plasma levels of estradiol in postmenopausal women significantly correlate with breast cancer risk,38 data assessing the relationship between plasma estrogen levels and outcome of therapy are sporadic. In one of the few studies they performed, Lønning et al38a reported that time to progression of breast cancer was shorter in patients with higher estrogen levels. Consistent with this, patients with higher body mass index have a poorer outcome although features other than higher estrogen levels may be influential in that relationship.

It would stand to reason that losing weight should be mandatory - having a proper BMI can be achieved.

And, at the time of ATAC study, there was no data about the toxicity of the drug for beyond 5 years. http://ascopubs.org/doi/full/10.1200/JCO.2002.06.020 Except for musculoskeletal disorders and fractures, the short-term side effects with anastrozole seen in the ATAC trial seemed to be comparable with or fewer than those seen with tamoxifen; however, there are no data available concerning the toxicity of any of the aromatase inhibitors administered for extended periods (ie, 5 years or more). There are no data concerning the late effects (after discontinuation of therapy) of a prolonged course of an aromatase inhibitor. The long-term effects of profound estrogen deprivation as seen with the third-generation aromatase inhibitors are unknown. In particular, concern has been raised that the adverse bone effects seen in the ATAC trial could become more common and/or severe with further follow-up.

But, many adverse reactions or AR's occur in a female body given the "FDA approved dose of 1mg", including loss of bone density, osteoporosis, or osteopenia: Doctors do baseline data on BONE DENSITY as the demise of bone is A GIVEN.

http://ascopubs.org/doi/10.1200/JCO.2005.03.903

All women receiving aromatase inhibitors should also have their BMD periodically measured and receive bisphosphonates according to published guidelines.2,15

The suppression of plasma estrogen has been associated with an accelerated rate of bone mineral loss and an increased risk of bone fracture (Simpson and Dowsett 2002; Geisler and Lønning 2008). Not only the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (Eastell et al. 2008), but also the Breast International Group (BIG) 1-98 trial (Zaman et al. 2011) and study of anastrozole with the bisphosphonate risedronate (SABRE) trial (Van Poznak et al. 2010) show that AIs have been associated with bone mineral loss and an increase of bone fracture.

And in one study: BMD changes in all patients. In all patients, within 6 months of hormone therapy, BMD decreased by 0.5% from baseline at the lumbar spine (solid line) and BMD decreased by 1.5% at the femoral neck (dot line). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486652/

And some studies are definitive on the fact that AI's cause a BMD decrease: AIs are definitely associated with the reduction of BMD (Eastell et al. 2008; Zaman et al. 2011). The reduction of plasma estrogen due to AIs has been associated with an accelerated rate of bone mineral loss and an increased risk of bone fracture.

Even Astra Zeneca, the drug's manufacturer notes BMD changes: https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/ARIMIDEX%20-%20Product-Monograph_002.pdf statistically significant changes were seen following 24 months of treatment

Including studies in Canada: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3476523/ On the other hand, it is well known that estrogens have a positive effect on bone metabolism by stimulating bone growth and inhibiting bone resorption, so their depletion in patients with endocrine-responsive breast cancer leads to increased bone demineralization and finally osteoporosis occurs. In fact, various studies demonstrated that estrogens deprivation caused by AI intake has a negative effect on bone health. Bone mineral density rapidly decreases resulting in increased risk of skeletal fragility.

And studies in Kuala Lumpur https://www.ncbi.nlm.nih.gov/pubmed/28397941 Conclusion: Anastrozole showed cytotoxic effects against the MCF7, HepG2, and PC3 cell lines as determined in-vitro by the MTT assay. The HCS technique also showed toxic effect towards MCF7. It is evident that anastrozole inhibits the aromatase enzyme preventing the aromatization mechanism; however, it has a toxic effect. (breast (MCF7), liver hepatocellular (HepG2), and prostate (PC3) cancer cells)

Patients should be informed of the risk of getting osteoporosis, and be informed about bisphosphonates to prevent or ward off a bone density decrease: Adjuvant endocrine therapy with an AI or androgen deprivation can be considered a risk factor for the development of osteopenia, osteoporosis, and bone fracture, which can be mitigated by appropriate bisphosphonate therapy. Clear identification of risk factors for osteoporosis in individual patients should aid treatment decisions about whether to use bisphosphonates when starting or switching to an AI or ADT. Patients need to be educated about this risk and other measures to avoid this complication,

Bone density tests should be given 12 - 24 months. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5384888/

In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<−2.0 or with a T-score of <–1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>−1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

Arthralgia, or pain in joints and bone are more frequent with AI's: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228389/ The incidence of arthralgias and myalgias appear to be about two-thirds higher with an AI than with tamoxifen or placebo but this can be helped if your Vitamin D stores is within a proper range: body vitamin D stores (53) and levels should be checked prior to starting AI treatment to make sure they are in the optimal range of 30–50 ng/ml

What percentage of women actually have joint related pain? Up to a whopping 50%

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. In studies of AI-related joint symptoms, anywhere from 20-50% of women on therapy reported the side effect. (9)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3810608/

In postmenopausal women, aromatase inhibitors are more effective than tamoxifen for reducing the recurrence of hormone-sensitive breast cancers [1–6]. However, work by our group and others has shown that up to 50 % of women on aromatase inhibitors report joint pain and or stiffness that starts or worsens after initiating treatment and causes significant morbidity [7–11]. These side effects can lead to early discontinuation of aromatase inhibitors and thus prevent women from obtaining the full survival benefit of this effective treatment for hormone-sensitive breast cancers [12, 13]. There is a need for safe, effective treatments to reduce this common drug-related toxicity.

Including weight gain: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.514.597&rep=rep1&type=pdf Adjuvant anastrozole therapy has been associated with weight gain (Hori et al. 2006),

But doctors seem to neglect the adverse reactions: http://ascopubs.org/doi/full/10.1200/jco.2014.56.9640

Other body parts are affected, such as the heart: http://onlinelibrary.wiley.com/doi/10.1111/j.1742-1241.2007.01587.x/full

It is possible that, if there is an intrinsic adverse effect of AIs on ischaemic heart disease, it might be due to estrogen depletion in the coronary arteries leading to loss of the vasodilatory response of estrogen to stress.

And, if you have a libido after your chemo and radiation, it may diminish after Arimidex: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228389/ Use of AIs is associated with a higher frequency of vaginal dryness, loss of libido and painful intercourse

And chemo brain? Combine that with AI brain - but doctors do not know the long term cognitive effects ...not if cognitive function returns! http://www.nursing.pitt.edu/long-term-trajectory-cognitive-function-related-anastrozole-use-women Five years of aromatase inhibitor therapy are prescribed for postmenopausal women with hormone receptor positive disease. However, the long term effects of this therapy on cognitive function are not known nor is it known whether cognitive function recovers after therapy ends. Finally, the impact of cognitive changes on the functional ability including the work ability of women with breast cancer has not been investigated. ...cognitive function deteriorated in these breast cancer cohorts up to 18 months post-anastrozole initiation suggesting that cognitive function continues to deteriorate with longer duration of therapy.

One study found Anastrozole to have more of a negative effect on cognitive impairment: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.514.597&rep=rep1&type=pdf Data forthe effects of adjuvant AItherapy on cognition are sparse, and more research is needed. In a study comparing patients from the ATAC trial with healthy controls, those receiving anastrozole were more impaired in a processing speed task (PZ0.032) and in a measure of immediate verbal memory (PZ0.026; Jenkins et al. 2004). Another pilot study found more severe cognitive impairment in women taking anastrozole versus those on tamoxifen (Bender et al. 2005), and exemestane was associated with more impaired word finding than tamoxifen (PZ0.0057) in the TEAM study (Asmar et al. 2005). Yet, in the prevention setting, the results from the cognitive substudy (nZ179) of the IBIS-II study found that anastrozole did not have a significant impact on cognitive functioning in postmenopausal women (Jenkins et al. 2006). More studies are needed to evaluate the long-term influence of AIs on cognition, dementia, and Alzheimer’s disease

And some effects to the brain can be...depression, sleep disturbances, and anxiety.

http://blogs.cancer.org/expertvoices/2015/10/27/does-hormone-therapy-for-breast-cancer-affect-the-brain/

Although few clinical studies focus on brain-related effects, we know that loss of estrogens can influence cognitive function, including verbal memory and fluency; can increase the likelihood of depression, anxiety, and sleep disturbances; and can lead to the loss of interest in sex. There is also evidence that it increases the risk of Alzheimer’s Disease. In the post-surgical breast cancer survivor, some of these can be confused with effects of surgery or radiation. Perhaps this is why the protocol is tossed one on top of the other - so a patient is not aware what causes which AR.

Doctors are aware that many women have adverse reactions (AR's), and that is why they quit the AI https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228389/ Of serious concern for prevention is the potential for increase in risk of bone fracture and cardiovascular disease related to long-term estrogen depletion with AIs. However, arthralgias, fatigue, dyspareunia, reduced libido and hot flushes may result in poor uptake and/or compliance. And in summary: Critical to the ultimate success of AIs in both the adjuvant and preventive settings will be management of adverse events, particularly bone mineral density loss, arthralgias and gynaecological sequelae.

When one is told to tell your doctor IF...then there is reason for concern as these conditions may be exacerbated or created with Arimidex: Your health care provider needs to know if you have any of these conditions: heart disease, circulation problems, a history of stroke or blood clot, severe liver disease, high cholesterol, osteoporosis, or low bone mineral density.

In the post-surgical breast cancer survivor, some of these can be confused with effects of surgery or radiation.

Risk Benefit must be weighed:

http://www.sciencedirect.com/science/article/pii/S1470204507700037

Results indicate that the increase in survival shown previously with the IES switch strategy is achieved at the expense of some detriment to skeletal health, so the risk-benefit ratio to women needs to be individually assessed

But, there is no guarantee the drug will work https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228389/ Even with an initial response to treatment, for women with metastatic disease, resistance eventually develops to AIs and clinical regrowth of tumour is observed. In most cases, the resistant cancer continues to be ER positive.

A must read study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228389/

Notes to be integrated: https://www.empowerpharmacy.com/drugs/anastrozole-capsules.html Anastrozole is well absorbed and distributed throughout the systemic circulation (85% bioavailability). Maximum plasma concentrations occur within 2 hours.7 Plasma concentrations approach steady-state levels by about the seventh day of once-daily dosing.

It is typically found in capsule or tablet forms of .25 mg, .5 mg, and 1 mg. The effects of Anastrozole can be very substantial, with a daily dose of 1 mg (commonly one tablet).

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