Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (698 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A triazole and benzonitrile derivative that is a selective non-steroidal aromatase inhibitor, similar to anastrozole. It is used in the treatment of metastatic or locally advanced breast cancer in postmenopausal women.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: 4,4'-(1H-1,2,4-triazol-1-yl-methylene)-bis(benzonitrile); CGS 20267; CGS-20267; CGS20267; Femara; Fémara.
Where it fits in the MeSH classification
- Broader topics
- Nitriles; Triazoles
Related concepts
Research landscape
PubMed indexes 3,083 records tagged with the MeSH heading “Letrozole” (counts retrieved 2026-10-31). 1,058 of them (34.3%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 1,187 records.
Reviews account for 411 records (13.3%) and meta-analyses for 89. Randomized controlled trials number 507 (16.4%) as a share of all records on the topic. Randomized trials make up a comparatively large share of this literature, which means many treatment questions have been tested directly.
Show the data
| Period | Records |
|---|---|
| through 1999 | 43 |
| 2000-2009 | 795 |
| 2010-2019 | 1,187 |
| 2020 onward | 1,058 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 411 | 13.3% |
| Meta-analyses | 89 | 2.9% |
| Randomized controlled trials | 507 | 16.4% |
Method: PubMed query "Letrozole"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up [1]
Abstract reading summary — source excerpts
- Opening excerpt
- PurposeIn the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.
- Closing excerpt
- gov: NCT01740427.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (185 words)
PurposeIn the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P MethodsIn this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).ResultsAfter a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P ConclusionsWith approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30632023 · DOI · PMC6438948
Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundFindings from randomized clinical trials may have limited generalizability to patients treated in routine clinical practice.
- Closing excerpt
- gov; NCT04176354.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (212 words)
BackgroundFindings from randomized clinical trials may have limited generalizability to patients treated in routine clinical practice. This study examined the effectiveness of first-line palbociclib plus letrozole versus letrozole alone on survival outcomes in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (MBC) treated in routine clinical practice in the USA.Patients and methodsThis was a retrospective observational analysis of electronic health records within the Flatiron Health Analytic Database. A total of 1430 patients with ≥ 3 months of follow-up received palbociclib plus letrozole or letrozole alone in the first-line setting between February 3, 2015, and February 28, 2019. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. Real-world progression-free survival (rwPFS) and overall survival (OS) were analyzed.ResultsAfter sIPTW adjustment, median follow-up was 24.2 months (interquartile range [IQR], 14.2-34.9) in the palbociclib group and 23.3 months (IQR, 12.7-34.3) in those taking letrozole alone. Palbociclib combination treatment was associated with significantly longer median rwPFS compared to letrozole alone (20.0 vs 11.9 months; hazard ratio [HR], 0.58; 95% CI, 0.49-0.69; P ConclusionsIn this "real-world" population of patients with HR+/HER2- MBC, palbociclib in combination with endocrine therapy was associated with improved survival outcomes compared with patients treated with letrozole alone in the first-line setting.Trial registrationClinicaltrials.gov; NCT04176354.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33761995 · DOI · PMC7989035
Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: the TransNEOS study [3]
Abstract reading summary — source excerpts
- Opening excerpt
- PurposeThe Recurrence Score test is validated to predict benefit of adjuvant chemotherapy.
- Closing excerpt
- 2% had RS ConclusionThe Recurrence Score test is validated to predict clinical response to neoadjuvant letrozole in postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (146 words)
PurposeThe Recurrence Score test is validated to predict benefit of adjuvant chemotherapy. TransNEOS, a translational study of New Primary Endocrine-therapy Origination Study (NEOS), evaluated whether Recurrence Score results can predict clinical response to neoadjuvant letrozole.MethodsNEOS is a phase 3 clinical trial of hormonal therapy ± adjuvant chemotherapy for postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer, after six months of neoadjuvant letrozole and breast surgery. TransNEOS patients had tumors ≥ 2 cm and archived core-biopsy samples taken before neoadjuvant letrozole and subsequently sent for Recurrence Score testing. The primary endpoint was to evaluate clinical (complete or partial) response to neoadjuvant letrozole for RS ResultsOf 295 TransNEOS patients (median age 63 years; median tumor size 25 mm; 66% grade 1), 53.2% had RS ConclusionThe Recurrence Score test is validated to predict clinical response to neoadjuvant letrozole in postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 30242578 · DOI · PMC6394785
Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer [4]
Abstract reading summary — source excerpts
- Opening excerpt
- The NeoPAL trial compares neoadjuvant letrozole-palbociclib (LP) with chemotherapy (CT) in 103 patients with high-risk, early luminal breast cancer.
- Closing excerpt
- These data provide a rationale for CT-sparing trials in this setting.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (155 words)
The NeoPAL trial compares neoadjuvant letrozole-palbociclib (LP) with chemotherapy (CT) in 103 patients with high-risk, early luminal breast cancer. At surgery, the NanoString BC360 proliferation score and Ki67 expression are reduced in both arms, together with upregulation of immune-related signatures. Overall, there is very little difference in the changes observed with LP as compared to CT, even in signatures related to response to estrogen and CDK4/6 manipulation. Deconvolution of bulk RNA sequencing (RNA-seq) data reveals high content at baseline in cancer cells, immunosuppressive cancer-associated fibroblasts, FOXP3+ CD4+ regulatory T lymphocytes, and TREM2+ macrophages. In contrast, myoepithelial cells, normal-like fibroblasts, FOLR2+ macrophages, and SELL+ CD4+ T lymphocytes accumulate after treatment in both arms. A low ROR score is observed at surgery in 63.3% and 43.5% of patients in the LP and CT arms, respectively. No 3-year breast cancer-specific survival events are observed in these patients. These data provide a rationale for CT-sparing trials in this setting.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41519129 · DOI · PMC12866096
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Polycystic ovarian syndrome-current pharmacotherapy and clinical implications [5]
- Research article First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis [6]
- Research article Letrozole for Female Infertility [7]
- Research article Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials [8]
- Research article A review of the physiology behind letrozole applications in infertility: are current protocols optimal? [9]
- Research article Higher ovulation rate with letrozole as compared with clomiphene citrate in infertile women with polycystic ovary syndrome: a systematic review and meta-analysis [10]
References
- Rugo HS, Finn RS, Diéras V, Ettl J, Lipatov O, Joy AA, et al.. Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. . 2019. PMID 30632023 · DOI · PMC6438948
- DeMichele A, Cristofanilli M, Brufsky A, Liu X, Mardekian J, McRoy L, et al.. Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice. . 2021. PMID 33761995 · DOI · PMC7989035
- Iwata H, Masuda N, Yamamoto Y, Fujisawa T, Toyama T, Kashiwaba M, et al.. Validation of the 21-gene test as a predictor of clinical response to neoadjuvant hormonal therapy for ER+, HER2-negative breast cancer: the TransNEOS study. . 2019. PMID 30242578 · DOI · PMC6394785
- Cottu P, Kieffer Y, Lemonnier J, D'hondt V, Duhoux FP, Callens C, et al.. Molecular and cellular composition changes after neoadjuvant letrozole and palbociclib in early luminal breast cancer. . 2026. PMID 41519129 · DOI · PMC12866096
- Rashid R, Mir SA, Kareem O, Ali T, Ara R, Malik A, et al.. Polycystic ovarian syndrome-current pharmacotherapy and clinical implications. Taiwan J Obstet Gynecol. 2022. PMID 35181044 · DOI
- Wang R, Li W, Bordewijk EM, Legro RS, Zhang H, Wu X, et al.. First-line ovulation induction for polycystic ovary syndrome: an individual participant data meta-analysis. Hum Reprod Update. 2019. PMID 31647106 · DOI
- Yang AM, Cui N, Sun YF, Hao GM. Letrozole for Female Infertility. Front Endocrinol (Lausanne). 2021. PMID 34220713 · DOI · PMC8245002
- Hu S, Yu Q, Wang Y, Wang M, Xia W, Zhu C. Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Arch Gynecol Obstet. 2018. PMID 29392438 · DOI
- Rose BI, Brown SE. A review of the physiology behind letrozole applications in infertility: are current protocols optimal?. J Assist Reprod Genet. 2020. PMID 32712844 · DOI · PMC7492298
- Tsiami AP, Goulis DG, Sotiriadis AI, Kolibianakis EM. Higher ovulation rate with letrozole as compared with clomiphene citrate in infertile women with polycystic ovary syndrome: a systematic review and meta-analysis. Hormones (Athens). 2021. PMID 34033068 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.