Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
Adjuvant treatment in postmenopausal women with hormone-receptor positive invasive early breast cancer* (Health Canada indication)
Extended adjuvant treatment in postmenopausal women with hormone-receptor positive invasive early breast cancer, after 5 years of tamoxifen treatment (Health Canada indication)
The Breast Clinical Practice Guideline (2014) recommends an aromatase inhibitor be used in postmenopausal patients with ER+ breast cancer (may have received adjuvant chemotherapy). Acceptable strategies for the use of the aromatase inhibitor include upfront treatment, switch strategy or extended adjuvant therapy.
*Aromatase inhibitors (AIs) have been used in the neoadjuvant setting in some clinical trials; AIs generally demonstrated higher breast conserving surgery rates with superior or similar response rates to tamoxifen. However, neoadjuvant AI use has not been approved by Health Canada
ODB Limited Use (letrozole - As an alternative to tamoxifen for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer for a maximum of five years)
ODB Limited Use (letrozole - Treatment of hormone receptor positive early breast cancer in postmenopausal women who have received 5 years of adjuvant tamoxifen therapy)
(Outpatient prescription in 2.5 mg tablets)
For extended adjuvant therapy, start within 3 months of completion of approximately 5 years of tamoxifen
Unless disease progression or unacceptable toxicity
Upfront treatment: For 5 years
Switch strategy: For 2-3 years (as a switch after 2-3 years of tamoxifen) for a total of 5 years of endocrine therapy
Extended adjuvant therapy: For 3-5 years, after completing 5 years of tamoxifen
Other Supportive Care:Patients receiving adjuvant letrozole should ensure adequate calcium intake (with supplementation as needed) and vitamin D supplementation. For more information about bone health via dietary and lifestyle measures, see pamphlet on Bone Health in Post-Menopausal Women.
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and could be considered.
Dosage with toxicity
Dosage in myelosuppression: No dosage adjustment required.
Mild to moderate
No dose adjustment needed, although exposure may ↑ by 37%
No data. Monitor patients closely and consider dose modification.
≥ 10 mL/min
No dose adjustment needed
< 10 mL/min
No data. Consider potential benefit-risk carefully.
Most Common Side Effects
Less Common Side Effects, but may be
Recommended Clinical Monitoring
- Bone mineral density; baseline and regular
- LH, FSH and/or estradiol levels in patients whose menopausal status is unclear or who become amenorrheic after chemotherapy; before starting letrozole and regularly during the first 6 months of treatment. Only confirmed postmenopausal patients should receive letrozole.;
- Serum cholesterol and lipids evaluation; baseline and regular
- Clinical assessment of fatigue, estrogen withdrawal symptoms, musculoskeletal, cardiovascular, thromboembolism, GI and GU effects, ophthalmic, etc.; regular
- Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
BIG 1-98 Collaborative Group, Mouridsen H, Giobbie-Hurder A, et al. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med 2009;361(8):766-76.
Eiermann W, Paepke S, Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Ann Oncol 2001;12(11):1527-32.
Ellis MJ, Coop A, Singh B, et al. Letrozole is more effective neoadjuvant endocrine therapy than tamoxifen for erbB-1– and/or erbB-2–positive, estrogen receptor–positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 2001;19(18):3808-16.
Goss PE, Ingle JN, Pater JL, et al. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. JCO 2008;26(12):1948-55.
Goss P, Ingle J, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. NEJM 2003;349(19):1793-802.
Regan MM, Neven P, Giobbie-Hurder A, et al. Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up. Lancet Oncol 2011;12(12):1101-8.
October 2017 removed sub-site adjuvant (under intent)
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.