Anastrozole
| Evidence Level: L1 | Predicted Indications: 6 |
Table of Contents
Anastrozole: From an Unrecorded Original Indication to Female Breast Carcinoma
One-Sentence Summary
The data provided does not record an original indication for Anastrozole, a non-steroidal aromatase inhibitor. The TxGNN model predicts it may be effective for female breast carcinoma, supported by 50 clinical trials and 20 publications, including large Phase 3 RCTs (ATAC, IBIS-II). Breast cancer is very likely already an approved use, so this is probably not true repurposing and should be confirmed against the label.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated (all approved-indication text fields are empty in the data) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 99.68% |
| Evidence Level | L1 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 (the five listed licenses are all ANDAs, i.e. generics) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the input. Anastrozole is a non-steroidal aromatase inhibitor that lowers estrogen synthesis. Estrogen drives hormone receptor-positive breast cancer in postmenopausal women, so the link between mechanism and disease is direct.
Phase 3 RCTs cited in the literature provide direct evidence. ATAC compared anastrozole with tamoxifen, and IBIS-II tested anastrozole against placebo for prevention. Because the input lists no original indication, breast cancer is very likely an on-label use. Treat this as a validation of the model rather than a new-use discovery until the label is checked.
Clinical Trial Evidence
The data contains 50 trials; the 10 most relevant to anastrozole itself are listed.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01602380 | Phase 3 | Completed | 462 | Fulvestrant 500 mg vs anastrozole 1 mg in postmenopausal women with hormone receptor-positive advanced breast cancer and no prior hormonal therapy; endpoint is disease progression |
| NCT00143390 | Phase 3 | Completed | 298 | Exemestane vs anastrozole as initial hormonal therapy in advanced/recurrent breast cancer; non-inferiority on time to progression |
| NCT00291759 | Phase 3 | Completed | 3858 | ARNO: after 2 years of tamoxifen, switch to anastrozole vs continued tamoxifen; event-free survival |
| NCT00543127 | Phase 3 | Terminated | 870 | Fulvestrant for 3 years plus anastrozole for 5 years vs anastrozole alone as adjuvant therapy |
| NCT00887380 | Phase 3 | Unknown | 2023 | Anastrozole started before and continued during radiotherapy vs delayed until after; local recurrence |
| NCT00784862 | Phase 3 | Completed | 9358 | Pharmacokinetic interaction of anastrozole and tamoxifen alone or combined; not an efficacy trial |
| NCT00274469 | Phase 2 | Completed | 205 | Fulvestrant vs anastrozole as first-line hormonal treatment in advanced disease |
| NCT00259090 | Phase 2 | Completed | 120 | Fulvestrant plus anastrozole vs each alone before surgery; biomarker anti-tumour effects |
| NCT00255463 | Phase 2 | Completed | 185 | Anastrozole plus placebo vs anastrozole plus gefitinib as neoadjuvant therapy; proliferation biomarker |
| NCT01972984 | Phase 2 | Completed | 20 | Short-term neoadjuvant anastrozole; changes in ER, PR, HER2 and Ki67 in the tumour (small study) |
Literature Evidence
The data contains 20 publications; the 10 most relevant are listed.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 15639680 | 2005 | RCT | Lancet | ATAC: 9366 postmenopausal women; anastrozole significantly prolonged disease-free survival vs tamoxifen (575 vs 651 events) |
| 31839281 | 2020 | RCT | Lancet | IBIS-II: long-term results of anastrozole vs placebo for breast cancer prevention |
| 26686313 | 2016 | RCT | Lancet | IBIS-II DCIS: anastrozole vs tamoxifen for preventing locoregional and contralateral breast cancer after excised DCIS |
| 9024711 | 1997 | RCT (Phase 3) | Cancer | Anastrozole 1 mg and 10 mg vs megestrol acetate in 386 postmenopausal women with advanced breast cancer who progressed after tamoxifen |
| 28415634 | 2017 | Meta-analysis | Oncotarget | Pooled RCTs comparing anastrozole vs tamoxifen as adjuvant therapy for efficacy and toxicity |
| 30499075 | 2020 | Meta-analysis | Pathol Oncol Res | Endocrine therapy for DCIS after breast-conserving surgery and radiotherapy; includes 2 tamoxifen vs anastrozole trials |
| 16439860 | 2006 | Review | Oncology | Role of anastrozole from advanced disease to early disease and prevention |
| 19445563 | 2009 | Review | Expert Opin Pharmacother | Comparison of anastrozole, letrozole and exemestane in early breast cancer |
| 28614542 | 2017 | Review | Rev Assoc Med Bras | Anastrozole in chemoprevention and treatment of breast cancer |
| 32701512 | 2020 | Pharmacogenomic study | JCI Insight | GWAS from the MA.27 trial (anastrozole vs exemestane) and additional mechanisms of anastrozole action |
US Market Information
The data lists 20 licenses in total; 5 are shown. All approved-indication text is empty in the data.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ANDA079220 | ANASTROZOLE (AvPAK) | Tablet | Not stated in data |
| ANDA078921 | Anastrozole (Zydus Pharmaceuticals USA Inc.) | Tablet, coated | Not stated in data |
| ANDA090568 | Anastrozole (A-S Medication Solutions) | Tablet | Not stated in data |
| ANDA212434 | Anastrozole (Aurobindo Pharma Limited) | Tablet, film coated | Not stated in data |
| ANDA090568 | Anastrozole (PD-Rx Pharmaceuticals, Inc.) | Tablet | Not stated in data |
Cytotoxicity
Anastrozole is used against a cancer indication, but it is an endocrine (hormonal) agent, not a conventional cytotoxic chemotherapy.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Endocrine therapy (non-steroidal aromatase inhibitor); not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Registered trials study bone density and fracture risk (NCT00122356, NCT00421447, NCT00859560); other items per package insert |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Please refer to the package insert for safety information. Warnings and contraindications were not available in the data.
Registered trials examine these adverse-effect areas, but the results are not in the data:
- Bone loss and fracture
- Endometrial changes
- Hepatotoxicity (fatty liver)
- Cognitive function
- Aromatase inhibitor-associated musculoskeletal symptoms
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Multiple completed Phase 3 trials and large RCTs (ATAC, IBIS-II) directly support anastrozole in breast cancer, which meets the L1 criterion. However, the original indication and MOA are missing from the data, and the safety data gaps block safety screening. Breast cancer is probably an existing approved use.
To proceed, the following is needed:
- Download and parse the FDA package insert to confirm whether breast cancer is already on-label; if so, reclassify this candidate as not true repurposing (DG001)
- Obtain the mechanism of action from DrugBank (DG002)
- Obtain package insert warnings and contraindications to complete safety screening (DG001, blocking)
The other five predictions (neuroblastoma, vertebral anomalies with endocrine and T-cell dysfunction, ganglioneuroblastoma, retroperitoneal neoplasm, monocytic leukemia) are all Hold. They rest on model scores alone (L5), or in one case a single case report (L4), with no plausible mechanistic link identified.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.