Anastrozole
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Anastrozole: From Breast Cancer (Registered Indication) to Female Breast Carcinoma
One-Sentence Summary
Anastrozole is a non-steroidal aromatase inhibitor registered in Singapore as an oral tablet. The registration records compiled for this report do not include the approved indication text. The TxGNN model predicts it is effective for female breast carcinoma, which is an established use rather than a true new indication. This direction is supported by 29 clinical trials (including several completed Phase 3 trials) and 20 publications (including large randomised trials such as ATAC, IBIS-II and FALCON).
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the data compiled for this report (the approved indication text is blank in all licences) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L1 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 11 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the compiled data. From the available assessment, anastrozole is a third-generation non-steroidal aromatase inhibitor. It blocks the conversion of androgens to oestrogens and lowers circulating oestrogen in postmenopausal women. This directly targets oestrogen-driven growth in hormone receptor-positive breast cancer.
The predicted indication is already an established clinical use. The high TxGNN score is consistent with both the mechanism and the clinical evidence. This is on-label use, not true repurposing.
The other nine predictions (for example neuroblastoma, ganglioneuroblastoma, monocytic and myeloid leukaemia, rhabdomyosarcoma) have no clinical trials and no supporting literature. They are computational predictions only, with no validated link to aromatase inhibition, and are not recommended for further action (Hold).
Clinical Trial Evidence
The list below shows the most relevant trials of the 29 identified. Phase 3 trials with direct anastrozole data are prioritised.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00784680 | Phase 3 | Completed | 308 | Quality of life with Arimidex vs tamoxifen vs combination as adjuvant therapy in postmenopausal women |
| NCT00327769 | Phase 3 | Completed | 234 | Fulvestrant 250 mg vs anastrozole 1 mg as second-line therapy in ER+ advanced breast cancer |
| NCT00143390 | Phase 3 | Completed | 298 | Exemestane vs anastrozole as initial hormonal therapy in advanced or recurrent breast cancer (non-inferiority) |
| NCT00301457 | Phase 3 | Completed | 1914 | 6 vs 3 years of adjuvant anastrozole after 2–3 years of tamoxifen |
| NCT00300508 | Phase 3 | Completed | 856 | 3 further years of anastrozole vs no treatment after 5 years of adjuvant hormone therapy |
| NCT02246621 | Phase 3 | Active, not recruiting | 493 | Non-steroidal aromatase inhibitor (anastrozole or letrozole) plus abemaciclib vs placebo in HR+/HER2− advanced breast cancer |
| NCT03425838 | Phase 3 | Active, not recruiting | 1050 | SONIA: aromatase inhibitor plus CDK4/6 inhibitor in first vs second line |
| NCT00256217 | Phase 2 | Completed | 42 | Anastrozole chemoprevention in DCIS and early invasive breast cancer |
| NCT04272801 | Phase 2 | Active, not recruiting | 84 | Pre-operative endocrine therapy in older women with early-stage breast cancer, to inform radiotherapy decisions |
| NCT00784940 | Phase 3 | Completed | 308 | Effects of Arimidex, tamoxifen and the combination on bone mineral density and metabolism |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15639680 | 2005 | RCT | Lancet | ATAC trial (9,366 women): after 5 years, anastrozole significantly prolonged disease-free survival compared with tamoxifen |
| 31839281 | 2020 | RCT | Lancet | IBIS-II long-term results: anastrozole vs placebo for breast cancer prevention in high-risk women |
| 27908454 | 2016 | RCT | Lancet | FALCON phase 3: fulvestrant 500 mg vs anastrozole 1 mg in HR+ advanced breast cancer without prior endocrine therapy |
| 42384406 | 2026 | RCT | JAMA Surgery | NSABP B-35: lumpectomy margins and local recurrence in DCIS, with randomisation to anastrozole or tamoxifen |
| 17138220 | 2006 | Meta-analysis | Lancet Oncology | Switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early breast cancer |
| 41632158 | 2025 | Cohort | JAMA Network Open | Comparative outcomes of anastrozole, letrozole and exemestane in postmenopausal breast cancer |
| 31615937 | 2020 | Clinical study | Clin Cancer Res | neoMONARCH: abemaciclib plus anastrozole in the neoadjuvant setting (phase II) |
| 20923259 | 2010 | Review | Expert Opin Drug Saf | Anastrozole as adjuvant therapy for HR+ breast cancer, with greater efficacy than tamoxifen in several trials |
| 16439860 | 2006 | Review | Oncology | Role of anastrozole across the breast cancer continuum, from advanced disease to prevention |
| 17033446 | 2006 | Case report | Eur J Gastroenterol Hepatol | First reported case of anastrozole-induced hepatotoxicity in an elderly woman |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN09433P | ARIMIDEX TABLET 1 mg | Film-coated tablet | Not stated |
| SIN14627P | ANASTROZOLE SANDOZ FILM COATED TABLET 1MG | Film-coated tablet | Not stated |
| SIN14864P | ANZONAT FILM-COATED TABLET 1 mg | Film-coated tablet | Not stated |
| SIN15618P | ANASTROZOLE STADA FILM COATED TABLET 1 MG | Film-coated tablet | Not stated |
| SIN16144P | ANABREZ ANASTROZOLE FILM COATED TABLET USP 1MG | Film-coated tablet | Not stated |
All 11 registrations are valid single-ingredient oral products (10 film-coated tablets and 1 plain tablet).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Hormonal therapy (non-steroidal aromatase inhibitor); not a conventional cytotoxic agent |
| Myelosuppression Risk | Low (not a typical effect of this class) |
| Emetogenicity Classification | Low |
| Monitoring Items | Bone mineral density, lipid profile and cardiovascular risk, liver function; please also refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Contraindications (knowledge-graph associations, not label text): myocardial ischaemia and coronary artery disease. These come from drug–disease links in the TxGNN knowledge graph and need confirmation against the approved label.
- Hepatotoxicity: one published case report describes anastrozole-induced liver injury.
- Class effects flagged in the trials: bone density loss and effects on blood vessel function were studied in several of the trials above.
- Drug Interactions: 100 potential interactions were identified, all with an unspecified severity level. Examples include bupropion, omeprazole, pantoprazole, metformin, glimepiride, simvastatin, morphine, prednisone and acetylsalicylic acid. The clinical significance of each needs separate review.
Package insert warnings and contraindications were not available for this report. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Anastrozole in breast cancer is supported by multiple completed Phase 3 trials and large randomised trials (ATAC, IBIS-II, FALCON), so the evidence level is L1. The indication is established, so this is confirmation of on-label use rather than new repurposing. The remaining nine predictions have no clinical support and should stay on Hold.
To proceed, the following is needed:
- Package insert warnings and contraindications (from the HSA website), which are required for safety screening
- Approved indication text for the Singapore licences, to confirm the original indication
- Mechanism of action data from DrugBank
- Guardrails: restrict use to postmenopausal women with hormone receptor-positive disease, monitor bone density and cardiovascular risk, and manage musculoskeletal adverse effects
- Review of the contraindication signals (myocardial ischaemia, coronary artery disease) and the interactions listed above
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.