Letrozole
| Evidence Level: L5 | Predicted Indications: 4 |
Table of Contents
Letrozole: Nipple carcinoma
One-Sentence Summary
Letrozole is an aromatase inhibitor that lowers estrogen production. The TxGNN model predicts it may be useful for nipple carcinoma, with a score of 0.9976. No clinical trials are registered for this condition, and the 8 publications found are mostly case reports. The evidence level is L5, because no study has tested letrozole in nipple carcinoma.
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 |
| Canada Market Status | Marketed (marketed DINs: 18 of 20; dormant: 2) |
| Number of DINs | 20 (marketed: 18) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Letrozole is known as an aromatase inhibitor, a drug class that blocks the conversion of androgens to estrogens and is used in hormone-driven breast conditions.
Nipple carcinoma is a breast cancer subtype or location. If the tumour is hormone receptor-positive, aromatase inhibition is plausible by extension from other breast cancers. This is only a theoretical link. No trial is specific to this entity, and the available literature is limited to case reports and one neoadjuvant endocrine therapy report in neuroendocrine carcinoma of the breast.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 33120755 | 2020 | Cohort / case report | Medicine | Neoadjuvant endocrine therapy in poorly differentiated neuroendocrine carcinoma of the breast; no standard treatment exists and the effect of endocrine therapy was unclear beforehand |
| 41607681 | 2026 | Case report | Clinical Case Reports | Nipple-originating solid papillary carcinoma in situ in a 73-year-old woman; standard diagnosis and treatment evidence is limited |
| 40395253 | 2025 | Case report | Cureus | Axillary recurrence after breast cancer with bloody nipple discharge |
| 39682607 | 2024 | Case report | Diagnostics (Basel) | Synchronous metastatic infra-mammary accessory breast cancer and ipsilateral breast cancer |
| 34495428 | 2021 | Case report | Surgical Case Reports | Accessory breast cancer in the inframammary region |
| 42305961 | 2026 | Case report | Frontiers in Medicine | Synchronous accessory breast cancer, papillary thyroid carcinoma and nasal papilloma |
| 42040393 | 2026 | Case report | Clinical Case Reports | Tall cell carcinoma of the breast with reverse polarity and IDH1 R132 mutation |
| 42416948 | 2026 | Case report | Cureus | Imaging features of florid lobular carcinoma in situ |
These reports describe related breast conditions. None tests letrozole in nipple carcinoma.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02231384 | FEMARA | Not listed | Not listed |
| 02309114 | PMS-LETROZOLE | Not listed | Not listed |
| 02343657 | TEVA-LETROZOLE | Not listed | Not listed |
| 02358514 | APO-LETROZOLE | Not listed | Not listed |
| 02344815 | SANDOZ LETROZOLE | Not listed | Not listed |
Safety Considerations
- Drug Interactions: 100 potential interactions were identified. The only one rated Moderate in the data is aprepitant. Others listed, with the severity unspecified, include calcitriol, glimepiride, lansoprazole, dolasetron, granisetron, famotidine, acetylsalicylic acid, pantoprazole, morphine and metformin.
- Conditions of concern: Liver failure, cirrhosis, osteoporosis (including postmenopausal), hyperbilirubinemia (including hereditary forms and Gilbert syndrome) and cerebrovascular disorder are flagged as conditions needing caution. Known adverse effects of letrozole include bone loss, arthralgia and menopausal symptoms.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (0.9976), but the evidence level is L5. No study has tested letrozole in nipple carcinoma, and the literature is limited to case reports. The mechanistic link is plausible only if the tumour is hormone receptor-positive.
To proceed, the following is needed:
- Confirmation of hormone receptor status in nipple carcinoma cases, and any clinical data on aromatase inhibitor use in this entity
- Detailed mechanism-of-action data
- Package insert warnings and contraindications from Health Canada
- A safety review for bone health and liver function in the intended population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.