Letrozole
| Evidence Level: L5 | Predicted Indications: 4 |
Table of Contents
Letrozole: Nipple carcinoma
One-Sentence Summary
Letrozole is an oral aromatase inhibitor (estrogen-synthesis blocker) marketed in Australia. Its approved indication is not recorded in the local data compiled for this report. The TxGNN model predicts it may be useful for nipple carcinoma, but there are no registered clinical trials and no study testing letrozole in this disease. The evidence level is L5 (model prediction only), and the 8 publications found are case reports on related breast conditions.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Nipple carcinoma |
| TxGNN Prediction Score | 0.9976 |
| Evidence Level | L5 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for letrozole are not available in the data compiled for this report. Letrozole is known as an aromatase inhibitor. It lowers estrogen production, which matters for tumours whose growth is driven by hormone receptors.
Nipple carcinoma is a malignancy of the breast, and some breast cancers are hormone-receptor-positive, so estrogen suppression is mechanistically plausible. This reasoning depends on the tumour’s receptor status, which the data do not establish for nipple carcinoma.
The supporting evidence is thin. It consists of case reports and one small neoadjuvant endocrine therapy report in a rare neuroendocrine breast carcinoma. None of it tests letrozole in nipple carcinoma itself.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
All entries are case reports on breast or nipple-related tumours. None evaluates letrozole in nipple carcinoma.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33120755 | 2020 | Case report | Medicine | Neoadjuvant endocrine therapy in poorly differentiated neuroendocrine carcinoma of the breast, a rare cancer with no standard treatment. The abstract notes the effect of endocrine therapy is unclear. |
| 41607681 | 2026 | Case report | Clinical Case Reports | Solid papillary carcinoma in situ arising in the nipple of a 73-year-old woman. Standardised diagnostic and treatment evidence is limited. |
| 40395253 | 2025 | Case report | Cureus | Axillary recurrence after breast cancer surgery in a woman whose cancer was first detected through bloody nipple discharge. |
| 42040393 | 2026 | Case report | Clinical Case Reports | Tall cell carcinoma of the breast with reverse polarity and purulent nipple discharge, with an IDH1 R132 mutation. |
| 42416948 | 2026 | Case report | Cureus | Ultrasound features of florid lobular carcinoma in situ. |
| 34495428 | 2021 | Case report | Surgical Case Reports | Accessory breast cancer in the inframammary region. |
| 39682607 | 2024 | Case report | Diagnostics (Basel) | Metastatic inframammary accessory breast cancer with a synchronous ipsilateral breast cancer. |
| 42305961 | 2026 | Case report | Frontiers in Medicine | Synchronous accessory breast cancer, papillary thyroid carcinoma and inflammatory nasal papilloma. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 13939P | Femara 2.5 mg | Tablet 2.5 mg (oral) | Not available in the data compiled for this report |
This is a single-ingredient product, and it is currently valid.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Hormonal (endocrine) therapy, not a conventional cytotoxic agent |
| Myelosuppression Risk | Please refer to the Product Information (PI) warnings and precautions |
| Emetogenicity Classification | Please refer to the Product Information (PI) warnings and precautions |
| Monitoring Items | Please refer to the Product Information (PI) warnings and precautions |
| Handling Protection | Please refer to the Product Information (PI) warnings and precautions |
Safety Considerations
Label-based warnings and contraindications were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for these.
- Conditions flagged in the compiled data (not label text): liver failure, cirrhosis of liver, osteoporosis (including postmenopausal), hyperbilirubinemia (including hereditary forms and Gilbert syndrome), and cerebrovascular disorder. Bone loss and liver function deserve particular attention if use is considered.
- Drug interactions: The interaction check returned 100 potential interacting drugs. The one rated Moderate among those listed is aprepitant. Others listed, with an unrated severity, include calcitriol, glimepiride, lansoprazole, dolasetron, granisetron, famotidine, acetylsalicylic acid, pantoprazole, morphine, metformin, omeprazole, rosiglitazone, simvastatin, prednisone, triamcinolone, lactulose, nystatin, potassium chloride and loperamide.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (0.9976), but no study, trial or publication tests letrozole in nipple carcinoma, so the evidence level is L5. The available literature is limited to case reports on related breast conditions and cannot support a change in practice.
To proceed, the following is needed:
- Hormone-receptor status data for nipple carcinoma, to confirm whether estrogen suppression is relevant
- Clinical studies (or at least systematic case series) of aromatase inhibitors in this disease
- Mechanism-of-action data for letrozole
- Label-based warnings and contraindications from the TGA Product Information
- A safety monitoring plan covering bone health and liver function
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.