Tamoxifen + Letrozole for Fertility Preservation in Breast Cancer

(TALES Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Mitchell Rosen, M.D.

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: University of California, San Francisco

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing two medication combinations to help women with breast cancer preserve their fertility. It focuses on women with a specific type of breast cancer and aims to find out which combination helps produce more mature eggs. The medications work by managing hormone levels and stimulating the ovaries. Tamoxifen and letrozole have been used to safely manage hormone levels in breast cancer patients undergoing fertility preservation.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves ovarian stimulation and oocyte retrieval, it's best to discuss your current medications with the trial team or your doctor.

What data supports the idea that Tamoxifen + Letrozole for Fertility Preservation in Breast Cancer is an effective drug?

The available research shows that letrozole, when compared to tamoxifen, improves the chances of staying free from breast cancer for longer periods in postmenopausal women. Letrozole is also better at preserving the breast during treatment. Additionally, a specific protocol using letrozole with tamoxifen has been developed for fertility preservation in women with breast cancer. This suggests that the combination of these drugs is effective for both treating breast cancer and preserving fertility. ^{1 2 3 4 5}

What safety data is available for the combination of Tamoxifen and Letrozole in breast cancer treatment?

The safety data for Letrozole and Tamoxifen, used individually or in combination, indicates that Letrozole is associated with a higher incidence of bone fractures, osteoporosis, and myocardial infarction, while Tamoxifen has a higher risk of endometrial proliferation, endometrial cancer, and thromboembolic events. Letrozole also required more patients to use lipid-lowering medications compared to Tamoxifen. These findings are based on clinical trials evaluating their use in breast cancer treatment. ^{1 3 4 6 7}

Is the drug Letrozole, Tamoxifen a promising treatment for fertility preservation in breast cancer?

Yes, Letrozole and Tamoxifen are promising drugs for fertility preservation in breast cancer. They help improve survival rates and reduce the risk of cancer returning, while also supporting fertility preservation. ^{2 3 8 9 10}

Eligibility Criteria

This trial is for adults over 18 who have been newly diagnosed with breast cancer and wish to preserve fertility before starting chemotherapy. They must want to undergo ovarian stimulation and egg retrieval.

Inclusion Criteria

New breast cancer diagnosis

Has not yet begun chemotherapy

Desires to undergo ovarian stimulation and oocyte retrieval prior to cancer treatment

Treatment Details

Interventions

• Letrozole (Aromatase Inhibitor)
• Tamoxifen (Selective Estrogen Receptor Modulator)

Trial Overview The study is testing the effectiveness of two drugs, Tamoxifen and Letrozole, in increasing the number of eggs retrieved for preservation from patients with estrogen-sensitive tumors before they start cancer treatment.

Participant Groups

Group I: ER Positive - Tamoxifen Experimental Treatment 1 Intervention

Group II: ER Positive - Letrozole Experimental Treatment 1 Intervention

Group III: ER Negative Active Control 1 Intervention

Letrozole is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

🇪🇺 Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

🇨🇦 Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California at San Francisco San Francisco, CA

Who Is Running the Clinical Trial?

University of California, San Francisco Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. [2022] The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone.

2. Italy pubmed.ncbi.nlm.nih.gov

Phase II trial with letrozole to maximum response as primary systemic therapy in postmenopausal patients with ER/PgR[+] operable breast cancer. [2022] Letrozole is superior to tamoxifen in terms of response and breast preservation rates as primary systemic therapy (PST) in postmenopausal women with ER-positive early breast cancer. However, the optimum duration of endocrine PST remains uncertain.

3. Poland pubmed.ncbi.nlm.nih.gov

A specific controlled ovarian stimulation (COS) protocol for fertility preservation in women with breast cancer undergoing neoadjuvant chemotherapy. [2022] The authors present a novel and specific controlled ovarian stimulation protocol for fertility preservation in women with estrogen-positive receptor breast cancer undergoing neoadjuvant chemotherapy. The protocol foresees random start ovarian stimulation and the use of letrozole associated to tamoxifen.

4. England pubmed.ncbi.nlm.nih.gov

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. [2021] On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor-positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76-1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen.

5. United States pubmed.ncbi.nlm.nih.gov

Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study. [2022] Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy.

6. Netherlands pubmed.ncbi.nlm.nih.gov

The evolving role of letrozole in the adjuvant setting: first results from the large, phase III, randomized trial BIG 1-98. [2022] Tamoxifen has been a standard adjuvant therapy, despite its limited 5-year efficacy window and risk of thromboembolism and endometrial malignancy. The potent aromatase inhibitor letrozole (Femara) has emerged as a viable alternative to tamoxifen for the treatment of advanced, metastatic breast cancer, as well as in the neoadjuvant and extended adjuvant settings. Here we describe the first efficacy and safety analysis of BIG 1-98, a large, randomized, independently conducted clinical trial designed specifically to assess and compare the efficacy of sequential or up-front use of letrozole and/or tamoxifen as adjuvant therapy for patients with early breast cancer. The analysis reported here combined the monotherapy arms of letrozole and tamoxifen with the truncated sequential arms. Patients randomized to letrozole had a 19% reduction in the risk of a disease-free survival event (hazard ratio 0.81; P=0.003), especially reducing distant metastases (hazard ratio 0.73; P=0.0012). These results establish letrozole as part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer.

7. England pubmed.ncbi.nlm.nih.gov

Efficacy of first-line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer. [2018] To compare the efficacy, in regard to time to progression (TTP) and objective response rate (ORR), of letrozole (Femara; Novartis Pharma AG; Basel Switzerland), an oral aromatase inhibitor, with that of tamoxifen (Tamofen; Leiras OY; Turku, Finland) as first-line therapy in younger (/=70 years) postmenopausal women with advanced breast cancer.

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA.17. [2022] National Cancer Institute of Canada Clinical Trials Group trial MA.17 randomly assigned 5,187 postmenopausal, hormone-receptor-positive patients with early breast cancer who completed 5 years of tamoxifen to receive either letrozole or placebo. At 30 months median follow-up, letrozole significantly improved disease-free survival (DFS) in all patients and overall survival (OS) in node-positive patients. Breast cancer incidence increases with age and more than 1,300 women age 70 years or older were enrolled onto MA.17, making it ideal to explore the benefits, toxicities, and quality of life (QOL) impact of letrozole on older women.

9. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of letrozole or tamoxifen coadministered with a standard stimulation protocol on fertility preservation among breast cancer patients. [2022] To assess the effects of letrozole or tamoxifen coadministration on fertility preservation treatment outcomes.

10. England pubmed.ncbi.nlm.nih.gov

Late risk of relapse and mortality among postmenopausal women with estrogen responsive early breast cancer after 5 years of tamoxifen. [2022] Letrozole after 5 years of adjuvant tamoxifen results in a significant reduction in risk of recurrence from estrogen receptor (ER) positive breast cancer. An individualized estimate of the risk of relapse and death after 5 years of tamoxifen could improve decisions regarding extended hormonal therapy.