Letrozole for Breast Cancer

Overseen By Meghan R. Flanagan

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Washington

Must be taking: Aromatase inhibitors

Must not be taking: Hormonal contraceptives

Disqualifiers: Metastatic disease, prior breast cancer therapy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3-10 weeks

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a specific gene mutation might affect the success of letrozole, a medicine used to stop the growth of breast cancer cells. It focuses on postmenopausal women with early-stage (I-III) breast cancer that is estrogen-receptor positive, meaning the cancer grows in response to estrogen. The trial aims to determine if this genetic mutation reduces the treatment's effectiveness. Women with a breast tumor larger than 1 cm who haven't received previous breast cancer treatments might be suitable candidates. Participants will take letrozole and provide saliva samples to help researchers assess the treatment's effectiveness. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had hormonal therapy for breast cancer treatment or prevention within 1 year prior to joining the study. Also, you should not be using hormonal contraceptives within 6 months of diagnosis.

What is the safety track record for letrozole?

Research has shown that letrozole is generally well-tolerated by patients. One study found that after five years of use, the safety results were positive, with most side effects being manageable. Common side effects included hot flashes and joint pain, while serious reactions were rare.

The FDA has also approved letrozole for treating certain types of breast cancer, indicating its general safety. Although some patients may experience mild discomfort, serious side effects are uncommon. This makes letrozole a trusted choice for many undergoing breast cancer treatment. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Letrozole is unique because it targets breast cancer by inhibiting aromatase, an enzyme responsible for estrogen production, which many breast cancers rely on to grow. Unlike older treatments that might not specifically target this pathway, letrozole provides a more focused approach to reducing estrogen levels. Researchers are excited about letrozole because it can be taken orally, offering a convenient option compared to treatments requiring hospital visits. Additionally, it offers flexibility in treatment duration, ranging from 14 to 70 days, allowing for tailored patient care based on individual needs.

What is the effectiveness track record for letrozole in treating breast cancer?

Research has shown that letrozole, the treatment under study in this trial, effectively treats breast cancer by significantly lowering the risk of recurrence. One study found that letrozole reduced the chances of cancer returning, with patients experiencing a 25% lower risk compared to those not taking it. Another study revealed that 73.8% of women taking letrozole remained disease-free after 8 years. Additionally, letrozole improved overall survival rates compared to tamoxifen, another breast cancer medication. This evidence supports letrozole's effectiveness in managing breast cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Meghan R. Flanagan

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for postmenopausal women aged 18 or older with stage I-III breast cancer that hasn't been treated yet. Participants must be able to take oral medication, have a tumor at least 1cm in size, ER+ and HER2-negative breast cancer. They should not have had hormonal therapy for breast cancer within the last year and must be candidates for surgical resection.

Inclusion Criteria

Ability to take oral medication and be willing to adhere to the study intervention.

It's okay if you have used birth control pills or hormone replacement therapy before. You can also use vaginal preparations.

Postmenopausal as defined by at least one of the following: Age >= 60 years; Age < 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; or serum estradiol and follicle stimulating hormone levels within the local laboratory's normal reference range for postmenopausal females; Documented bilateral oophorectomy.

Exclusion Criteria

Pre-treatment tumor biopsy sample not likely to provide adequate tissue sections for biomarker assays.

Subjects who have received any prior therapy for breast cancer, including radiotherapy, surgery, and cytotoxic and endocrine treatments for the current breast cancer, or received any therapy within the last 1 year for a prior primary breast cancer.

The subject must not have had hormonal therapy for breast cancer treatment or for breast cancer prevention within 1 year prior to study enrollment. (Note: Synchronous breast, cancer (including bilateral breast cancer) at separate sites is permissible, provided the patient does not receive medical treatments for breast cancer or radiation therapy to the ipsilateral breast during the study intervention period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive letrozole orally once daily for 21 days, with a minimum of 14 days and a maximum of 70 days of total treatment, and undergo collection of saliva samples

3-10 weeks

Follow-up

Participants are monitored for changes in Ki67, estrogen receptor alpha, intracellular androgen, estrogen levels, ER beta, and 3betaHSD1 expression up to 9 months after surgery

9 months

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole

Trial Overview The study is examining how a gene mutation (HSD3B1) affects the effectiveness of letrozole, an aromatase inhibitor used in treating hormone-sensitive breast cancer. It involves collecting biospecimens and administering questionnaires to understand treatment outcomes.

How Is the Trial Designed?

Group I: Treatment (letrozole) Experimental Treatment 3 Interventions

Patients receive letrozole PO QD for 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of saliva samples. If tumor resection occurs before or after day 22, letrozole administration must occur for a minimum of 14 days and a maximum of 70 days of total treatment.

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

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Letrozole is an effective treatment for postmenopausal women with early-stage or advanced hormone-sensitive breast cancer, showing a 43% reduction in disease recurrences when used as extended adjuvant therapy beyond standard tamoxifen treatment.

In advanced breast cancer, letrozole outperformed tamoxifen in terms of time to disease progression (9.4 months vs. 6.0 months) and has a similar tolerability profile, making it a recommended first-line therapy according to treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in postmenopausal women with breast cancer. Simpson, D., Curran, MP., Perry, CM.[2018]

In a study of 4,922 postmenopausal women with hormone receptor-positive early breast cancer, letrozole significantly improved overall survival (OS) compared to tamoxifen, with an 18% reduction in the risk of death.

Letrozole also demonstrated better disease-free survival (DFS) and time to distant recurrence (TDR), indicating it is a more effective adjuvant treatment option for this patient group.

NCBI (Pubmed)

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. Colleoni, M., Giobbie-Hurder, A., Regan, MM., et al.[2022]

Letrozole is more effective than tamoxifen for adjuvant therapy in postmenopausal women with hormone-responsive early breast cancer, and it is well tolerated by patients.

Extended therapy with letrozole after tamoxifen treatment is more effective than placebo, making it a valuable treatment option while ongoing trials investigate the best duration and comparison with other aromatase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. Keating, GM.[2021]

In a study of 1065 postmenopausal women with early breast cancer receiving letrozole, immediate treatment with zoledronic acid significantly increased lumbar spine bone mineral density (BMD) by 5.7% compared to a delayed treatment strategy, which resulted in bone loss.

Both immediate and delayed zoledronic acid regimens were well tolerated, but the immediate group experienced more bone pain due to acute-phase reactions, highlighting the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective inhibition of aromatase inhibitor-associated bone loss by zoledronic acid in postmenopausal women with early breast cancer receiving adjuvant letrozole: ZO-FAST Study results. Bundred, NJ., Campbell, ID., Davidson, N., et al.[2022]

The FACE trial is a large-scale study involving 4000 postmenopausal women with hormone receptor-positive, node-positive breast cancer, comparing the efficacy and safety of letrozole and anastrozole over a treatment period of up to 5 years.

The primary goal of the trial is to assess disease-free survival (DFS), while secondary objectives include evaluating overall survival (OS) and the time to distant metastases, which will provide comprehensive insights into the effectiveness of both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FACE trial: letrozole or anastrozole as initial adjuvant therapy? Jonat, W., Mundhenke, C.[2018]

Letrozole is a new non-steroidal aromatase inhibitor approved in Japan for treating postmenopausal women with breast cancer, particularly effective for those with steroid receptor positive or receptor-unknown locally advanced or metastatic cases.

The drug is generally well-tolerated, with mostly mild side effects such as hot flashes and fatigue, and has shown beneficial results in large international studies for post-surgical endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. Tsukagoshi, S.[2018]

Letrozole is a highly potent aromatase inhibitor that significantly reduces circulating estrogen levels by over 75-95% in postmenopausal patients, making it effective for treating advanced breast cancer.

In clinical trials, letrozole demonstrated anti-tumor activity in patients with advanced breast cancer who had previously undergone other treatments, and it was well tolerated with no significant hormonal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole (CGS 20267), a new oral aromatase inhibitor for the treatment of advanced breast cancer in postmenopausal patients. Trunet, PF., Bhatnagar, AS., Chaudri, HA., et al.[2019]

Letrozole significantly outperformed tamoxifen in delaying disease progression and treatment failure in postmenopausal women with advanced breast cancer, with median times of 9.4 months versus 6.0 months, respectively.

While the overall survival (OS) was slightly better for letrozole (34 months) compared to tamoxifen (30 months), this difference was not statistically significant; however, letrozole did show improved survival rates during the first two years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III study of letrozole versus tamoxifen as first-line therapy of advanced breast cancer in postmenopausal women: analysis of survival and update of efficacy from the International Letrozole Breast Cancer Group. Mouridsen, H., Gershanovich, M., Sun, Y., et al.[2022]

In a study of 907 postmenopausal women with advanced breast cancer, letrozole was found to be more effective than tamoxifen, showing a longer time to progression (TTP) in both younger (<70 years) and older (≥70 years) patients.

Letrozole also demonstrated a significantly higher objective response rate (ORR) in older patients (38% vs. 18% for tamoxifen), while the ORR in younger patients was similar for both treatments (26% for letrozole vs. 22% for tamoxifen).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of first-line letrozole versus tamoxifen as a function of age in postmenopausal women with advanced breast cancer. Mouridsen, H., Chaudri-Ross, HA.[2018]

Letrozole is an effective aromatase inhibitor for postmenopausal women with hormone-sensitive breast cancer, showing significant tumor reduction and well-tolerated at low daily doses, as confirmed by recent phase III clinical studies.

It has demonstrated superior efficacy and lower toxicity compared to tamoxifen in first-line therapy for advanced breast cancer, and is also a viable option for second-line treatment after tamoxifen failure, with potential benefits in early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of letrozole (Femara(R)) in breast cancer therapy: A clinical review. Crucitta, E., Locopo, N., Silvestris, N., et al.[2019]

Letrozole, a type 2 aromatase inhibitor, effectively reduces estrogen levels in postmenopausal women, leading to improved disease-free survival in breast cancer patients compared to other treatments like tamoxifen.

The drug is generally well-tolerated, though it may cause side effects such as hot flushes, joint pain, and a potential increased risk of fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: advancing hormone therapy in breast cancer. Lee, RJ., Armstrong, AC., Wardley, AM.[2018]

Citations

1. drugs.com drugs.com/medical-answers/success-rate-femara-breast-cancer-3546039/

What is the success rate for Femara in breast cancer? In the BIG 1-98 trial, 73.8% of women who received letrozole alone had a disease-free survival at 8 years, compared to 70.4% of women who ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.69.2871

Comparative Efficacy and Safety of Adjuvant Letrozole ... Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10637036/

Ten-year update: NRG Oncology/National Surgical ... Letrozole statistically significantly reduced breast cancer–free interval events (HR = 0.75, 95% CI = 0.62 to 0.91; P = .003; absolute difference in cumulative ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2001225/

A decade of letrozole: FACE - PMC Letrozole significantly reduced the risk of breast cancer recurrence (hazard ratio = 0.81; 95% confidence interval [CI] 0.70, 0.93; P = 0.003), especially the ...

5. cancer.gov cancer.gov/types/breast/research/letrozole-prevents-recurrence

Study Confirms Letrozole Prevents More Breast Cancer ... Women who received letrozole alone also had better overall survival at 8 years than women receiving tamoxifen alone (83.4 versus 81.2 percent).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10853028/

Long-term Follow-up and Safety of Patients after an Upfront ... We here report the primary efficacy and safety outcome of five years upfront therapy with letrozole. The therapy was indicated at the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3248775/

Approval Summary: Letrozole (Femara® Tablets) for ... Secondary endpoints included the OS duration, occurrence of distant recurrence, DDFS interval, and occurrence contralateral breast cancer. Safety endpoints ...

8. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2016.69.2871

Comparative Efficacy and Safety of Adjuvant Letrozole ... The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most ...

9. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044750

Aromatase Inhibitors and the Risk of Cardiovascular ... These drugs have been associated with favorable clinical outcomes, including decreased risks of all-cause and breast cancer–related mortality, ...

10. nejm.org nejm.org/doi/full/10.1056/NEJMoa2114663

Overall Survival with Ribociclib plus Letrozole in Advanced ... Median overall survival was 63.9 months (95% confidence interval [CI], 52.4 to 71.0) with ribociclib plus letrozole and 51.4 months (95% CI, ...