Effects of letrozole: A Synthesis of Findings from 20 Studies

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Original Abstract of the Article

Major Research Findings

Letrozole is an aromatase inhibitor that is effective in treating hormone-sensitive breast cancer in postmenopausal women. 13 The BIG 1-98 trial showed that letrozole was more effective than tamoxifen in preventing recurrence of breast cancer, and the effect was stronger in women with a higher risk of recurrence. 6 The MA.17 trial confirmed the benefits of letrozole after 5 years of tamoxifen, showing that letrozole can significantly reduce the risk of breast cancer recurrence in women who have already completed 5 years of tamoxifen treatment. 7 Letrozole has been shown to significantly decrease serum estradiol and estrone levels, which are crucial in preventing breast cancer growth. 3 However, letrozole may have a greater risk of bone loss and heart disease compared to tamoxifen. 6 Furthermore, letrozole can increase IGF-1 levels in the blood, which could potentially promote cancer growth. 11

In addition to treatment, letrozole also shows potential for breast cancer prevention. 15 Research suggests that even low and intermittent doses of letrozole can effectively suppress estrogen levels similar to standard doses, which might help reduce side effects while achieving the preventive effect. 15 However, more research is needed to confirm whether these alternative dosing schedules are non-inferior to standard doses.

Letrozole has been shown to have a positive impact on sperm production in men with non-obstructive azoospermia or cryptozoospermia. 14 The study demonstrated that letrozole increased sperm concentration and motility in men with low testosterone levels.

Benefits and Risks

Benefits Summary

Letrozole is an effective drug for treating hormone-sensitive breast cancer in postmenopausal women. It has been shown to be more effective than tamoxifen in preventing breast cancer recurrence, particularly in women at higher risk. 13 Furthermore, letrozole has a lower risk of blood clots and uterine fibroids compared to tamoxifen. 6 Letrozole significantly decreases serum estradiol and estrone levels, which are crucial in preventing breast cancer growth. 3 Letrozole may also have the potential to prevent breast cancer in postmenopausal women. 15 Low and intermittent doses of letrozole have been shown to be effective in suppressing estrogen levels, potentially reducing side effects while achieving the preventive effect. 15

Risks Summary

While letrozole is an effective drug, it also poses potential risks. Letrozole may increase the risk of bone loss and heart disease compared to tamoxifen. 6 Letrozole has been found to increase IGF-1 levels in the blood, which might promote cancer growth. 11

Comparison Across Studies

Commonalities

Several studies have shown that letrozole is effective in treating hormone-sensitive breast cancer in postmenopausal women. 13 Letrozole is more effective than tamoxifen in reducing estrogen levels. 10 Letrozole is a powerful inhibitor of estrogen production and significantly reduces serum estrone and estradiol levels. 3

Differences

Some studies suggest that letrozole may have a higher risk of bone loss and heart disease compared to tamoxifen. 6 Letrozole has been shown to increase IGF-1 levels in the blood, which might promote cancer growth. 11 However, these risks have not been definitively established in all studies. 6 Letrozole has been proven to have a lower risk of blood clots and uterine fibroids compared to tamoxifen. 6

Consistency and Contradictions in the Findings

Overall, the research findings consistently show that letrozole is an effective drug for treating hormone-sensitive breast cancer in postmenopausal women. 13 6 7 10 3 4 5 15 However, there is some inconsistency in the findings regarding the risks associated with letrozole. Some studies suggest that letrozole may have a higher risk of bone loss and heart disease compared to tamoxifen, while others do not show this. 6 Similarly, the increase in IGF-1 levels observed in some studies has not been consistently reported in others. 11

Implications for Daily Life

Letrozole is an important treatment option for hormone-sensitive breast cancer in postmenopausal women. If you have been diagnosed with this type of cancer, discuss with your doctor whether letrozole is a suitable treatment for you. 6 You should also discuss the potential risks and benefits of letrozole treatment, including bone loss, heart disease, and the possible increase in IGF-1 levels. 6 11

Limitations of Current Research

There are some limitations to the current research on letrozole. More research is needed to determine the long-term effects of letrozole, and to better understand how the effects of letrozole may vary between different patients. 6 Further research is also needed to clarify the potential risks associated with letrozole. 6 11

Future Research Directions

Future research should focus on understanding the long-term effects of letrozole, including its effects on bone health, cardiovascular health, and cancer recurrence. 6 11 Research should also identify factors that may predict how individual patients will respond to letrozole treatment. 6 11 In addition, more research is needed to evaluate the safety and effectiveness of different dosing regimens for letrozole, particularly for breast cancer prevention. 15 2

Conclusion

Letrozole is an effective drug for treating hormone-sensitive breast cancer in postmenopausal women. 13 6 7 10 3 4 5 It is important to discuss the potential risks and benefits of letrozole treatment with your doctor to make an informed decision. 6 11 Further research is needed to clarify the long-term effects and risks associated with letrozole. 6 11

Literature analysis of 20 papers
Positive Content
17
Neutral Content
2
Negative Content
1
Article Type
15
3
4
2
19
1.

The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels.

Author: BajettaE, FerrariL, CelioL, MarianiL, MiceliR, Di LeoA, ZilemboN, BuzzoniR, SpagnoliI, MartinettiA, BichisaoE, SeregniE

Increased IGF-I levels

Letrozole increased serum IGF-I levels in postmenopausal women with advanced breast cancer, but further studies are needed to confirm this finding and understand its clinical significance.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

2.

Double-blind, randomised, multicentre endocrine trial comparing two letrozole doses, in postmenopausal breast cancer patients.

Author: BajettaE, ZilemboN, DowsettM, GuillevinL, Di LeoA, CelioL, MartinettiA, MarchianòA, PozziP, StaniS, BichisaoE

Suppressed estrogen levels

Letrozole, an aromatase inhibitor, significantly suppressed oestrone and oestradiol levels in postmenopausal advanced breast cancer patients without affecting adrenal activity.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

3.

Influence of letrozole and anastrozole on total body aromatization and plasma estrogen levels in postmenopausal breast cancer patients evaluated in a randomized, cross-over study.

Author: GeislerJürgen, HaynesBen, AnkerGun, DowsettMitch, LønningPer Eystein

Suppressed aromatase
Suppressed estrogen levels
None mentioned

Letrozole is a more potent suppressor of total-body aromatization and plasma estrogen levels than anastrozole in postmenopausal women with metastatic breast cancer. Letrozole 2.5 mg once daily resulted in a greater reduction in plasma levels of estrone, estradiol, and estrone sulfate than anastrozole 1 mg once daily.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

4.

Letrozole versus tamoxifen in the treatment of advanced breast cancer and as neoadjuvant therapy.

Author: SmithIan E

Improved benefit
Improved progression
Improved response

Letrozole, an aromatase inhibitor, has been shown to be more effective than tamoxifen in the treatment of advanced breast cancer. Letrozole is superior to tamoxifen in terms of time to progression, objective response, and clinical benefit in both first-line and neoadjuvant treatment settings.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

5.

Adjuvant endocrine therapy for postmenopausal women with early breast cancer.

Author: IngleJames N

Breast cancer treatment

This study examined the use of aromatase inhibitors in the treatment of postmenopausal women with hormone receptor-positive early breast cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

6.

The use of early adjuvant aromatase inhibitor therapy: contributions from the BIG 1-98 letrozole trial.

Author: ForbesJohn F

Breast cancer treatment
Cardiac events
Skeletal events

The Breast International Group 1-98 trial (BIG 1-98) found that letrozole significantly increased disease-free survival (DFS) compared to tamoxifen in postmenopausal women with early breast cancer. The advantage for letrozole was particularly evident in women at increased risk of recurrence. Letrozole was generally well-tolerated and associated with fewer deaths than tamoxifen.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

7.

Preventing relapse beyond 5 years: the MA.17 extended adjuvant trial.

Author: GossPaul E

Breast cancer treatment
Bone metabolism

Letrozole, a third-generation aromatase inhibitor, has been shown to significantly reduce the risk of recurrent breast cancer (42%) and distant metastasis (40%) in postmenopausal women with hormone-receptor-positive breast cancer who have completed 5 years of tamoxifen therapy. The study, MA.17, also found that letrozole significantly improved overall survival in women with node-positive disease, reducing mortality by 39%. Letrozole was well-tolerated with minimal side effects.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

8.

Molecular response to aromatase inhibitor treatment in primary breast cancer.

Author: MackayAlan, UrruticoecheaAnder, DixonJ Michael, DexterTim, FenwickKerry, AshworthAlan, DrurySuzanne, LarionovAlexey, YoungOliver, WhiteSharon, MillerWilliam R, EvansDean B, DowsettMitch

Effective estrogen suppression

Aromatase inhibitors, such as anastrozole and letrozole, effectively suppress estrogen synthesis in postmenopausal women. Their molecular effects on human breast carcinomas in vivo require further investigation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

Author: RossiEmanuela, MorabitoAlessandro, Di RellaFrancesca, EspositoGiuseppe, GravinaAdriano, LaboniaVincenzo, LandiGabriella, NuzzoFrancesco, PacilioCarmen, De MaioErmelinda, Di MaioMassimo, PiccirilloMaria Carmela, De FeoGianfranco, D'AiutoGiuseppe, BottiGerardo, ChiodiniPaolo, GalloCiro, PerroneFrancesco, de MatteisAndrea

Endocrine effects

This study compared the endocrine effects of letrozole and tamoxifen in postmenopausal patients with hormone-responsive early breast cancer. While both drugs affected hormone levels, significant differences were observed, potentially explaining the higher efficacy of letrozole compared to tamoxifen.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

10.

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women.

Author: GibsonLorna, LawrenceDavid, DawsonClaire, BlissJudith

Tumor regression
Limited trial evidence

This review examines the use of aromatase inhibitors (AIs) in the treatment of advanced breast cancer. While AIs have shown similar tumor-regressing effects to other endocrine treatments, the evidence regarding their response rates and side effects is still limited.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

11.

A randomized, placebo-controlled trial (NCIC CTG MAP1) examining the effects of letrozole on mammographic breast density and other end organs in postmenopausal women.

Author: CiglerT, TuD, YaffeM J, FindlayB, VermaS, JohnstonD, RichardsonH, HuH, QiS, GossP E

Reduced estrogen levels
Decreased bone density
Increased IGF-1 levels

This multicenter, randomized, double-blind, placebo-controlled trial investigated the effects of letrozole, an aromatase inhibitor, on mammographic breast density. The study found that letrozole did not significantly reduce breast density.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

12.

Anastrozole and letrozole: an investigation and comparison of quality of life and tolerability.

Author: DixonJ Michael, RenshawLorna, LangridgeCarolyn, YoungOliver E, McHughMary, WilliamsLinda, MurrayJuliette, MacaskillE Jane, McCaigFiona, DixonOliver M, FallowfieldLesley J

Well tolerated

Anastrozole and letrozole are well-tolerated aromatase inhibitors with similar effects on quality of life.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause.

Author: ChirgwinJacquie, SunZhuoxin, SmithIan, PriceKaren N, ThürlimannBeat, EjlertsenBent, BonnefoiHervé, ReganMeredith M, GoldhirschAron, CoatesAlan S,

Improved disease free survival

Letrozole, an aromatase inhibitor, is effective in postmenopausal women but may be less beneficial in certain subpopulations with potential residual ovarian activity. This study analyzed data from the BIG 1-98 trial, focusing on younger women with natural menopause and those with chemotherapy-induced menopause. Contrary to initial concerns, the findings suggest that letrozole remains an effective treatment option even in these subpopulations.

Clinical Trial, Phase IIIA Phase III trial is a trial that further rigorously verifies the efficacy and safety of a new drug or treatment, whose efficacy and safety have been confirmed in a Phase II trial, in a large number of patients, and evaluates whether it is superior to existing treatments.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients: a pilot study.

Author: CavalliniGiorgio, BiagiottiGiulio, BolzonElisa

Increased sperm count
Side effects

Letrozole, an aromatase inhibitor, increased sperm count in azoospermic and cryptozoospermic patients with a low testosterone/estradiol ratio, suggesting potential for male infertility treatment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

15.

Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk.

Author: LópezAna Maria, PruthiSandhya, BougheyJudy C, PerloffMarjorie, HsuChiu-Hsieh, LangJulie E, LeyMichele, FrankDenise, TavernaJosephine A, ChowH-H Sherry

Breast cancer prevention
Side effects

A double-blind, randomized trial was conducted to assess the efficacy and side effects of low and intermittent doses of letrozole, an aromatase inhibitor, for breast cancer prevention in high-risk postmenopausal women. The study found that low and intermittent doses of letrozole are not inferior to standard dose in estrogen suppression and resulted in a similar side-effect profile.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

16.

Efficacy and Safety of Controlled Ovarian Stimulation With or Without Letrozole Co-administration for Fertility Preservation: A Systematic Review and Meta-Analysis.

Author: BonardiBenedetta, MassarottiClaudia, BruzzoneMarco, GoldratOranite, MangiliGiorgia, AnseriniPaola, SpinaciStefano, AreccoLuca, Del MastroLucia, CeppiMarcello, DemeestereIsabelle, LambertiniMatteo

Fertility preservation
Hormone-sensitive cancers

This systematic review and meta-analysis found that co-administering letrozole during controlled ovarian stimulation does not negatively impact efficacy and may reduce peak estradiol levels.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

17.

Does letrozole treatment have favorable effects on the lipid profile? A systematic review and meta-analysis of randomized clinical trials.

Author: CaiTao, Al-JubairiNashmi Naife, SantosHeitor O, de SouzaIvan G O, ChenYoudong

HDL-C reduction
Total cholesterol reduction

Letrozole, a medication used to treat breast cancer, was found to decrease levels of HDL cholesterol and total cholesterol in women. However, it did not have a significant effect on levels of LDL cholesterol or triglycerides. This suggests that letrozole may have some impact on lipid profiles, but further research is needed to understand its long-term effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

18.

Lack of cross-resistance between non-steroidal and steroidal aromatase inhibitors in breast cancer patients: the potential role of the adipokine leptin.

Author: BahramiNazli, JabeenShakila, TahiriAndliena, SauerTorill, ØdegårdHilde Presterud, GeislerStephanie Beate, GravdehaugBerit, ReitsmaLaurens Cornelus, SelsåsKnut, KristensenVessela, GeislerJürgen

Disease stabilization

Exemestane, an aromatase inactivator, can stabilize disease progression in patients with metastatic breast cancer who have previously responded to non-steroidal aromatase inhibitors like letrozole, suggesting that its efficacy goes beyond estrogen suppression.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

19.

Effects of letrozole cotreatment on endocrinology and follicle development in women undergoing ovarian stimulation in an antagonist protocol.

Author: PoulsenLiv C, WarzechaAgnieszka K, BülowNathalie S, BungumLeif, MacklonNicholas S, Yding AndersenClaus, SkoubySven O

Improved corpus luteum function
Improved follicle growth

Letrozole cotreatment during ovarian stimulation for in vitro fertilization (IVF) significantly suppressed estradiol levels and increased follicle diameter without affecting the recruitment of the next follicle cohort.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

20.

Influence of the anti-oestrogens tamoxifen and letrozole on thyroid function in women with early and advanced breast cancer: A systematic review.

Author: MarinaDjordje, RasmussenÅse Krogh, Buch-LarsenKristian, GillbergLinn, AnderssonMichael, SchwarzPeter

BC recurrence
Thyroid function

Tamoxifen and letrozole are anti-oestrogens used to prevent breast cancer recurrence. While their side effects are well-documented, their impact on thyroid function is less clear. This review explores the potential effects of tamoxifen and letrozole on thyroid function and their contribution to weight gain observed in breast cancer patients.

Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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