Limited Endocrine Therapy for Breast Cancer

(LALEAST Trial)

Overseen By Caroline Lohrisch, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: British Columbia Cancer Agency

Must be taking: Endocrine therapy

Disqualifiers: Other cancers, Prior breast cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 12

Duration: 2 years

290 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase II trial of 2 years of standard adjuvant endocrine therapy after low risk hormone receptor positive, HER2 negative, node negative breast cancer in women older than 50 at diagnosis. The study hypothesis is that reducing adjuvant endocrine therapy from 5 to 2 years in a population with low risk of breast cancer; as determined by histopathologic criteria and confirmed by low risk genomic analysis using Prosigna®; will be safe and acceptable to this population, and will not compromise the expected excellent breast cancer specific outcomes for this population.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it does require that you have not started endocrine therapy before enrolling.

What data supports the effectiveness of the drug Tamoxifen Citrate for breast cancer?

Tamoxifen has been a standard treatment for hormone-sensitive early breast cancer, helping to prevent recurrences and improve survival, although it may have side effects. It is particularly effective in preventing cancer in the opposite breast after surgery. ^{1 2 3 4 5}

Is Tamoxifen generally safe for humans?

Tamoxifen, used for breast cancer treatment, is generally well-tolerated but can have serious side effects like increased risk of endometrial cancer (cancer of the uterus lining) and blood clots. It also has mild side effects such as hot flashes and nausea, but it can improve bone health and reduce heart disease risk in postmenopausal women. ^{2 6 7 8 9}

How is the drug Tamoxifen Citrate different from other breast cancer treatments?

Tamoxifen Citrate is unique because it has been the standard endocrine therapy for breast cancer, especially in premenopausal women, due to its ability to block estrogen receptors, which can slow or stop the growth of hormone receptor-positive breast cancer. However, it can cause serious side effects like increased risk of endometrial hyperplasia (thickening of the uterus lining) and blood clots, leading to the development of alternative treatments like aromatase inhibitors. ^{1 3 10 11 12}

Research Team

Caroline Lohrisch, MC

Principal Investigator

BC Cancer

Eligibility Criteria

This trial is for women over 50 with a specific type of low risk, hormone receptor positive, HER2 negative breast cancer that hasn't spread. They must not have started endocrine therapy or had certain cancers in the last 5 years and should be expected to live at least another 5 years.

Inclusion Criteria

I am a woman over 50, diagnosed with breast cancer at any menopausal stage.

My breast cancer has a low Prosigna score, 40 or less.

My doctor believes I could live more than 5 years despite my other health issues.

Exclusion Criteria

Does not meet every inclusion criteria listed above

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard of care adjuvant endocrine therapy for two years, with flexibility to switch therapies if intolerable side effects develop. Participants are seen every six months and complete periodic quality of life questionnaires.

2 years

4 visits (in-person)

Follow-up

Participants have annual study visits until year 10, with periodic quality of life questionnaires and assessment of study endpoints.

8 years

8 visits (in-person)

Treatment Details

Interventions

• Tamoxifen Citrate

Trial Overview The trial tests if taking Tamoxifen Citrate for just two years instead of five is safe and effective for older women with low risk breast cancer as determined by histopathologic criteria and Prosigna® score.

Participant Groups

Group I: standard of care endocrine therapy for two years Experimental Treatment 1 Intervention

Standard of care adjuvant endocrine therapy for two years. for postmenopausal women, initial therapy will be aromatase inhibitor unless contraindicated, in which case tamoxifen may be used. For premenopausal and perimenopausal women, initial therapy will be tamoxifen unless contraindicated, in which case an lutenizing hormone releasing hormone (LHRH) agonist with / without aromatase inhibitor may be used.

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

NanoString Technologies, Inc.

Industry Sponsor

Trials

11

Recruited

2,100+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Findings from Research

Tamoxifen, while a long-standing treatment for early breast cancer, only prevents about half of relapses and can lead to serious side effects like endometrial hyperplasia and venous thromboembolism due to its estrogenic activity.

Aromatase inhibitors are emerging as a more effective alternative, showing benefits in various treatment settings, including extending therapy after tamoxifen and providing upfront adjuvant therapy, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant endocrine therapy in breast cancer. Management of early-risk relapse]. Chahine, G., Howayek, M., Atallah, D.[2013]

Tamoxifen is the standard treatment for postmenopausal women with hormone-sensitive early breast cancer, but it has side effects that have led researchers to look for safer alternatives.

Third-generation aromatase inhibitors like anastrozole, letrozole, and exemestane have shown better efficacy and a more favorable side effect profile compared to tamoxifen in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. Grana, G.[2018]

Aromatase inhibitors, such as anastrozole and letrozole, show superior efficacy and a better safety profile compared to tamoxifen for treating metastatic breast cancer, making them a preferred option in first- and second-line treatments.

The ATAC trial indicates that anastrozole not only improves disease-free survival in hormone receptor-positive patients but also reduces the risk of developing contralateral breast cancer, highlighting its effectiveness in postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in breast cancer: an update. Lake, DE., Hudis, C.[2018]

Only 27.4% of surveyed primary care physicians prescribed tamoxifen for breast cancer prevention in the past year, indicating that its use is not widespread among these doctors.

Factors influencing the decision to prescribe tamoxifen included personal connections to breast cancer, patient inquiries about the drug, and the belief that its benefits outweigh the risks, while concerns about endometrial cancer risk had less impact on prescribing decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription of tamoxifen for breast cancer prevention by primary care physicians. Armstrong, K., Quistberg, DA., Micco, E., et al.[2015]

Adjuvant endocrine treatment is crucial for postmenopausal women with hormone receptor-positive breast cancer, with options including tamoxifen and aromatase inhibitors, each having unique side effects.

For premenopausal women, tamoxifen is the standard treatment, and ongoing research is exploring the potential benefits of adding ovarian suppression to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for early-stage breast cancer. Burstein, HJ., Griggs, JJ.[2010]

References

1. Lebanon pubmed.ncbi.nlm.nih.gov

[Adjuvant endocrine therapy in breast cancer. Management of early-risk relapse]. [2013]

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

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. [2018]

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

Aromatase inhibitors in breast cancer: an update. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

Incidence of contralateral breast cancer in Japanese patients with unilateral minimum-risk primary breast cancer, and the benefits of endocrine therapy and radiotherapy. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[CURRENT PERSPECTIVE ON SYSTEMIC THERAPY FOR BREAST CANCER]. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Economic evaluation of using a genetic test to direct breast cancer chemoprevention in white women with a previous breast biopsy. [2022]

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

Shifting paradigms in hormonal therapy for breast cancer. [2020]

8. France pubmed.ncbi.nlm.nih.gov

[Surveillance of patients treated with tamoxifen]. [2016]

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

Risks and benefits of tamoxifen therapy. [2013]

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

Prescription of tamoxifen for breast cancer prevention by primary care physicians. [2015]

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

Adjuvant hormonal therapy for early-stage breast cancer. [2010]

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

Historical perspective on hormonal therapy of advanced breast cancer. [2022]