But because aromatase inhibitors are so much more effective than tamoxifen in postmenopausal women, researchers wondered if there were a way to successfully treat premenopausal women diagnosed with hormone-receptor-positive, early-stage breast cancer with an aromatase inhibitor.
Results from the SOFT Suppression of Ovarian Function Trial study published in suggest that premenopausal women diagnosed with hormone-receptor-positive breast cancer can be successfully treated with the aromatase inhibitor Aromasin if their ovarian function is suppressed. You should not take an aromatase inhibitor if you are breastfeeding, pregnant, trying to get pregnant, or if there is any chance that you could be pregnant. Aromatase inhibitors may cause damage to developing embryos. You should use an effective non-hormonal type of birth control — such as condoms, a diaphragm along with spermicide, or a non-hormonal I.
Ask your doctor which type of non-hormonal birth control would be best for you, as well as how long you should use this type of birth control after you stop taking an aromatase inhibitor. A number of studies have compared aromatase inhibitors with tamoxifen to see which type of medicine was more effective in treating early-stage, hormone-receptor-positive breast cancer in postmenopausal women.
Based on the results, most doctors recommend that after initial treatment surgery and possibly chemotherapy and radiation therapy :. Aromatase inhibitors tend to cause fewer serious side effects than tamoxifen, such as blood clots, stroke, and endometrial cancer.
But aromatase inhibitors can cause more heart problems , more bone loss osteoporosis , and more broken bones than tamoxifen, at least for the first few years of treatment. If you and your doctor are considering an aromatase inhibitor as part of your treatment plan, you may want to ask your doctor about having a bone density test to see if a bone strengthening medicine might be necessary while you're taking the aromatase inhibitor.
Advanced breast cancer is also known as metastatic breast cancer, or cancer that has spread from the breast to the lymph nodes and other parts of the body, such as the bones, liver, and lungs. Arimidex is also FDA-approved as a first-line treatment for advanced hormone-unknown breast cancer, or breast cancer that may or may not be receptive to hormone therapy.
Aromasin is not approved for advanced hormone-unknown breast cancer, although it may sometimes be used off-label for this purpose. Arimidex and Aromasin are effective breast cancer treatments. A healthcare provider should be consulted to determine the best option. Anastrozole and exemestane, the active ingredients in Arimidex and Aromasin, respectively, have been compared in head-to-head clinical trials.
One study published in The Lancet Oncology compared anastrozole, exemestane, and letrozole. The study found that these aromatase inhibitors were similarly effective for treating hormone receptor-positive breast cancer. The study also found that five years of aromatase inhibitor therapy was not superior to two years of tamoxifen therapy followed by the use of an aromatase inhibitor for three years.
Another study published in the Journal of Clinical Oncology found that both aromatase inhibitors are similarly effective as adjuvant treatments for postmenopausal breast cancer. The main deciding factor between aromatase inhibitors may be the tolerability of the drugs regarding potential side effects. The same study found that exemestane could be an option for up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer without the need for two to three years of tamoxifen treatment first.
Arimidex is a brand-name medication that is also available in a generic form. The generic form may be a cheaper option than the brand-name form. Arimidex is usually covered by Medicare and insurance plans. Aromasin is also a brand-name medication that is available in a generic form.
Most Medicare and insurance plans will help cover the cost of Aromasin. Arimidex and Aromasin can cause similar side effects such as hot flashes, joint pain, and muscle pain.
As aromatase inhibitors, both medications can also cause decreased bone mineral density and an increased risk of osteoporosis. According to the FDA label, the most common side effects of Arimidex are hot flashes, weakness, joint pain, sore throat, high blood pressure, depression, nausea, rash, osteoporosis, insomnia, headache, and back pain.
According to the FDA label, the most common side effects of Aromasin are hot flashes, fatigue, joint pain, headache, insomnia, nausea, increased appetite, and increased sweating. When both medications were compared in a head-to-head clinical trial , Arimidex was found to cause more effects on bone mineral density osteoporosis , vaginal bleeding, and high cholesterol levels.
Aromasin was found to cause more liver function abnormalities. This may not be a complete list of adverse effects that can occur. Please refer to your doctor or healthcare provider to learn more. Arimidex should be avoided with tamoxifen. Taking tamoxifen with Arimidex can lower levels of Arimidex in the body, which could lead to decreased effectiveness of Arimidex. Aromasin does not interact with tamoxifen. Estrogen-containing products like birth control pills or other contraceptives can decrease the effectiveness of Arimidex and Aromasin.
This is due to the fact that estrogen therapies increase the levels of estrogen while Arimidex and Aromasin decrease the levels of estrogen in the body. The effects of estrogen treatment counteract the effects of aromatase inhibitors. Drugs that act as CYP3A4 inducers can decrease levels of Aromasin in the body, which can lead to decreased effectiveness of Aromasin. Medications that act as CYP3A4 inducers include rifampin, phenytoin, and carbamazepine. As aromatase inhibitors, Arimidex and Aromasin have anti-estrogen effects.
Estrogen helps promote bone growth. Unfortunately, these methods are labor-intensive, and analyses are usually limited to small numbers of patients. Plasma estrogen measurement is a cruder but simpler method that allows screening of much larger numbers of patients. Table 1 provides a comparison of the total body aromatase inhibition of third-generation AIs compared with the first- and second-generation compounds.
Among third-generation AIs, letrozole seems to produce the most extensive estrogen suppression. Results from an intrapatient crossover study revealed that letrozole 2. This level of suppression is superior to that previously reported for anastrozole using the same methods: Direct comparisons of reanalyzed samples also found superior suppression of plasma estrogen levels with letrozole compared with anastrozole Geisler et al , , E2 average suppression by Recently, Dixon et al confirmed that letrozole reduces plasma estrogen levels to a greater degree than does anastrozole at clinical doses.
The results of these two translational studies, Geisler et al and Dixon et al , raise the question of whether differences in potency translate into differences of clinical importance. Although it has been postulated by some authors that aromatase inhibition above a defined level f. However, because of the very different side-effect profiles of aminoglutethimide and letrozole when given in the clinically established doses, with the latter being much less toxic, an influence of compliance problems during aminoglutethimide treatment on the study results cannot be excluded.
In contrast, the corresponding study comparing letrozole 0. In conclusion, a suboptimal dosage of anastrozole cannot be totally ruled out. However, this problem cannot be solved by simply increasing the daily dose of anastrozole. This would require to repeat all phase III trials with the higher dose of anastrozole to evaluate clinical responses and even more important that is, side effects.
With patents expiring for all aromatase inhibitors in a short-time frame, this is probably not of any interest for the involved pharmaceutical company. Letrozole is the only AI that has been demonstrated to possess significantly superior efficacy to tamoxifen in the neoadjuvant setting, and is the only AI to have received approval from several countries for use in this setting.
Objective responses for anastrozole and tamoxifen occurred in In the intent-to-treat ITT population, surgery became feasible after 3 months of hormonal therapy in In contrast to these findings, the Immediate Preoperative Anastrozole, Tamoxifen, or Combined With Tamoxifen trial did not find any significant benefit with anastrozole compared with tamoxifen. The outcome of patients in need of neoadjuvant therapy may also be altered by the frequency of complete pathological responses during therapy with an AI.
Although complete pathological responses have been observed in a study published by Dixon et al , these were not found in the corresponding group of patients treated with anastrozole Dixon et al , It compared anastrozole alone or in combination with tamoxifen with tamoxifen monotherapy following breast cancer surgery. Combination therapy was not significantly more beneficial than tamoxifen alone, so the combination arm was terminated early, leaving further analyses limited to patients Baum et al , The key efficacy endpoints across treatment settings are summarised in Table 2.
Based on the superiority of letrozole vs tamoxifen at As a result of the crossover, in addition to the ITT analysis, a censored analysis was performed to account for crossover patients Mouridsen et al , However, the IBCSG concluded that early crossover to letrozole possibly biased the ITT analysis in favour of tamoxifen and the censored analysis in favour of letrozole, making accurate assessments of OS difficult.
To adjust for this potential bias, an additional inverse probability of censoring weighted analysis was carried out to provide a more accurate estimate of the clinical benefit of letrozole. It is important to note that with the emergence of significantly improved treatments, the issue of crossover is being addressed in many trials and is not unique to this trial. The potential effect of CYP2D6 genetic variants on clinical response in tamoxifen-treated breast cancer patients has recently gained much interest.
CYP2D6 is predominantly responsible for the 4-hydroxylation of tamoxifen leading to its most active metabolites, 4-hydroxytamoxifen and endoxifen Dehal and Kupfer, The reported differences between the tamoxifen arms and the AI-arms in the large clinical phase III studies in early breast cancer have to be re-evaluated in the light of these novel findings. Indirect information from the ATAC and BIG 1—98 trials indicates that differences in clinical efficacy exist between anastrozole and letrozole in the initial adjuvant setting.
The most common type of recurrence seen 2 to 3 years post surgery is DM, a well-recognised predictor of breast cancer survival Saphner et al , ; Mansell et al , In contrast, exploratory analysis of the ATAC trial confirmed that most of the early benefit with anastrozole was not in the prevention of distant disease; at 2.
Thus, the novel increased dosage of fulvestrant is a promising endocrine treatment option in all settings of breast cancer, and data for patients with early breast cancer are awaited in a short-time frame.
Although the ATAC and BIG 1—98 trials have provided an extensive data set for anastrozole and letrozole in early breast cancer, no head-to-head trial of these two AIs has been conducted in this setting.
The ongoing FACE trial was designed to prospectively address potential efficacy and safety differences O'Shaughnessy, This phase III open-label, randomised, multicenter study includes node-positive patients randomised to receive either early adjuvant letrozole or anastrozole. The primary objective is to compare DFS at 5 years.
Secondary objectives are to assess safety, OS, time to DM, and time to contralateral breast cancer. The trial was designed to differentiate between the two drugs in the shortest possible time by enrolling patients at increased risk of early recurrence of breast cancer, so that the number of events required to initiate analysis will be obtained more quickly. The results may help refine treatment strategies for PMW with breast cancer. Because of the extended duration of adjuvant endocrine therapy, patient tolerability issues and their potential influence on compliance and therapeutic outcome are important themes.
All in all, third-generation AIs seem to have very similar toxicity profiles. Most side effects are explained by the general estrogen deprivation, predictable and similar to those of natural menopause.
They may include hot flashes, arthralgia, osteoporosis, fractures, hypercholesterolemia, and cardiovascular events see Table 3 for an overview. Side effects like thromboembolic events and endometrial cancer that are well established for antiestrogen therapy, are rarely seen during therapy with aromatase inhibitors.
Although novel antiestrogens like raloxifene are less toxic compared with tamoxifen when tested head-to-head in women at increased risk for development of breast cancer, raloxifene has recently been shown to be less effective in preventing breast cancer, too Vogel et al , At a mean follow-up of These results support a greater lipid-lowering effect of tamoxifen rather than a detrimental effect of letrozole.
Safety analysis at a median of In conclusion, blood lipids seem to be slightly and equally increased during therapy with all third-generation AIs anastrozole, letrozole, and exemestane when compared directly with tamoxifen, because of the lipid-lowering effects of tamoxifen and not because of a lipid-increasing effect of AIs. In the adjuvant setting, the rate of muculoskeletal symptoms is significantly higher for all third-generation AIs compared with tamoxifen.
These events generally emerge early in treatment, are low grade and improve with time. In addition, AIs cause a significant increase in both bone resorption and formation.
Osteoporosis and increased fracture rates occur in some patients when using AIs Table 3. Although preclinical studies suggested that bone loss may be less during treatment with a steroidal AI exemestane compared with non-steroidal AIs anastrozole and letrozole , there is no evidence at all from clinical trials confirming these hypotheses.
In contrast, a randomised trial of healthy volunteers demonstrated that all AIs have a similar effect on burn turnover McCloskey et al , Because of the early screening for osteopenia and osteoporosis whenever AIs are implemented in patients with early breast cancer and liberal use of calcium, vitamin D, and bisphosphonates, the issue of bone loss seems to be solved for the majority of patients.
Acquired, as well as de novo , resistance to aromatase inhibition remains a major concern in clinical practice. Future research will seek to improve our understanding of how to treat AI-resistant breast cancers and, perhaps more importantly, how to prevent the onset of AI-induced resistance.
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