Evista aka Raloxifene : the SERM we don't hear about...
- Reserach in Progress
- Dec 27, 2017
- 5 min read
After endless hours of researching the AR's and SE's of Arimidex, I turned to researching other drugs, including SERMS.
One popular SERM (Select Estrogen Receptor Modulater is Tamoxifen, however, Tamoxifen seems to cause a host of AR's and SE's that make it challenging for many women to continue their use. Some possible AR's of Tamoxifen are uterine cancer, decrease in memory, pain in joints and muscles. So, I've searched to find something a bit ... better.
SERM's act differently on the body, in that they don't act systemically (whole body) as an AI does. They work on just SELECTED parts of the body, generally the breasts (high estrogen areas).
On to Raloxifene. This drug sounds promising on many fronts.
It seems to have a lot of benefit, for very few side effects. In fact, when compared to the toxicity of an AI, and the SE's of Tamoxifen, Raloxifene appears tame, albeit a bit weaker in some respects. My personal comments are in GREEN.
Here is research data on Raloxifene:
What were the STAR results in terms of reducing invasive breast cancer risk? https://www.cancer.gov/types/breast/research/star-trial-results-qa The initial results of STAR showed that raloxifene and tamoxifen were equally effective in reducing invasive breast cancer risk in postmenopausal women at increased risk of the disease after an average of 47 months. After an average of 81 months, (5 years of medication and 21 months of followup) women in the tamoxifen group had 247 cases of invasive breast cancer in 9,736 women and women in the raloxifene group had 310 cases of invasive breast cancer in 9,754 women. This means that in raloxifene reduces risk of invasive breast cancer by about 38 percent compared to tamoxifen reducing breast cancer by about 50 percent over almost 7 years; or, raloxifene is about 76 percent as effective as tamoxifen in reducing risk for invasive breast cancer over almost 7 years. For those women in the trial with a uterus, the women in the raloxifene group developed 45 percent fewer uterine cancers during the trial, a statistically significant reduction: 65 of 4,739 women in the tamoxifen group developed uterine cancers compared to 37 of the 4,717 women in the raloxifene group. Tamoxifen is known to increase a woman's chance of developing uterine cancer (mostly in the lining of the uterus or endometrium) by two to three times compared to a woman not taking the drug The annual incidence rate of uterine cancer is 2.25 per 1,000 women taking tamoxifen and 1.23 per 1,000 women taking raloxifene after almost 7 years. -- In STAR, women in the raloxifene group had 28 percent fewer deep-vein thromboses (blood clots in a major vein) and 20 percent fewer pulmonary embolisms (blood clots in the lung) than women on tamoxifen:
Raloxifene has fewer serious side effects than tamoxifen:
https://www.medpagetoday.com/hematologyoncology/breastcancer/3477
When the results were announced at the press conference in April the message was that the study was a clear win for Evista because the drug was said to have fewer serious side-effects—a lower risk of thromboembolic events or cataracts and less likelihood of hot flashes and night sweats. Moreover, there was less likelihood of uterine cancer with 23 cases reported in the Evista arm versus 36 in the tamoxifen arm.
There were fewer cases of noninvasive breast cancer in the tamoxifen group (57 cases) than in the raloxifene group (80 cases) (incidence, 1.51 vs 2.11 per 1000; RR, 1.40; 95% CI, 0.98-2.00). The difference did not reach statistical significance. However, this study may have been underpowered to detect such a difference.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2971719/
In particular, raloxifene binds to the ER, leading to estrogen-agonist effects in some targets (bone and lipid metabolism) and estrogen-antagonist effects in others (breast and endometrium).25 Raloxifene has anti-estrogenic effects in the breast, competitively blocking estrogen-induced DNA transcription26 and inhibiting the growth of estrogen-stimulated mammary cancers in animals.27
Raloxifene has anti-estrogenic effects in the breast, competitively blocking estrogen-induced DNA transcription27 and inhibiting the growth of estrogen-stimulated mammary cancers in animals.27Moreover, raloxifene reduces mammographic breast density64 and breast cancer proliferative indices66and plays a protective role in decreasing the incidence of breast cancer.
The MORE trial showed a breast cancers risk reduction of 65% (RR 0.35) and 76% (RR 0.24) among the patients with invasive cancer. The risk reduction was limited to ER-positive tumors (RR 0.10), with no decrease occurring in ER-negative tumors (RR 0.88).67 Continued follow-up of MORE participants showed an ongoing breast cancer risk reduction in postmenopausal women treated with raloxifene: the risk reduction was 72% (RR 0.28) and 84% (RR 0.16) of the ER-positive breast cancers.68
Raloxifene benefits in several ways:
https://www.ncbi.nlm.nih.gov/pubmed/18534794/
Rationale for using raloxifene to prevent both osteoporosis and breast cancer in postmenopausal women.
this drug can be prescribed for clear indications, such as the management of osteoporosis, the prevention of fracture, and decreasing the incidence of invasive breast cancer, with careful monitoring for thromboembolism. It is reasonable to use raloxifene as an appropriate medicine that targets climacteric symptom-free postmenopausal women because of its overall favorable risk-benefit safety profile
Raloxifene has a positive effect on the central nervous system:
https://www.ucsf.edu/news/2005/04/6195/researchers-see-less-cognitive-impairment-women-taking-raloxifene-os
However, they wrote, given that other studies have shown that estrogen reduces the risk of Alzheimer's disease and cognitive impairment, it is most likely that raloxifene has an estrogen-like effect on the central nervous system
https://www.prnewswire.com/news-releases/lilly-announces-review-of-data-on-long-term-raloxifene-treatment-for-postmenopausal-osteoporosis-published-in-current-medical-research--opinion-127297028.html
EVISTA is an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator (SERM), which appears to act like estrogen in bone and to block the effects of estrogen in some tissues. It is an osteoporosis therapy for postmenopausal women that also reduces the risk of invasive breast cancer in postmenopausal women with osteoporosis.
So, why isn't Evista Raloxifene more widely prescribed? I asked this of my oncology doctor and the answer is that it is not as effective as Tamoxifin. When weighing data, one must decide if the side effects and adverse reactions to Tamoxifin and AI's are worth the extra percentage points. Ask your doctor about Evista - it may be a better choice for you.
Side Effects:
Cardiovascular: Very common (10% or more): Hot flashes/hot flushes/vasodilation (28.7%), increased blood pressure Common (1% to 10%): Varicose vein, venous thromboembolism (VTE) Other Very common (10% or more): Flu syndrome (16.2%), infection (15.1%), peripheral edema (14.1%) Common (1% to 10%): Chest pain, fever[Ref]MusculoskeletalVery common (10% or more): Arthralgia (15.5%), muscle spasms/leg cramps (12.1%)Common (1% to 10%): Myalgia, arthritis, tendon disorder[Ref]Respiratory Very common (10% or more): Sinusitis (10.3%), rhinitis (10.2%)Common (1% to 10%): Bronchitis, pharyngitis, increased cough, pneumonia, laryngitis[Ref] DermatologicCommon (1% to 10%): Rash, sweating[Ref] EndocrineCommon (1% to 10%): Breast pain/tenderness/enlargement[Ref] GastrointestinalCommon (1% to 10%): Nausea, diarrhea, dyspepsia, vomiting, flatulence, gastrointestinal disorder, gastroenteritis, abdominal pain[Ref] GenitourinaryCommon (1% to 10%): Vaginitis, urinary tract infection, cystitis, leukorrhea, uterine disorder, vaginal bleeding, endometrial disorder, vaginal hemorrhage, urinary tract disorder[Ref]HepaticCommon (1% to 10%): Cholelithiasis, cholecystectomyFrequency not reported: Slightly decreased platelet counts, moderate increases in AST and/or ALT[Ref]
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