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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether reducing hormone therapy from five years to two years is safe and effective for women with a low-risk form of breast cancer. It targets hormone receptor-positive, HER2-negative breast cancer that has not spread to the lymph nodes. Eligible participants are women over 50 who have been diagnosed with this specific cancer type and have not yet started hormone therapy. The study aims to determine if a shorter treatment period with Tamoxifen Citrate (a hormone therapy) can maintain good health outcomes while easing the burden on those affected. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that tamoxifen citrate, a common breast cancer treatment, is generally well-tolerated by many patients. Studies indicate that tamoxifen can lower the risk of invasive breast cancer by 40% and reduce the chance of dying from breast cancer by 57%. Another study found that women taking tamoxifen had a one-third lower risk of dying from breast cancer over 15 years.

However, like any medication, tamoxifen can have side effects. Common side effects may include hot flashes and a higher risk of blood clots. It's important to weigh these potential risks against the benefits. This treatment has been used successfully for many years to help prevent breast cancer from returning.

The current trial aims to shorten the treatment duration from the usual five years to two years. While specific safety data for this trial isn't available yet, tamoxifen's long history of use offers some reassurance about its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard of care for breast cancer, which often includes prolonged endocrine therapy with aromatase inhibitors or Tamoxifen, this treatment protocol is exploring a limited two-year course of endocrine therapy. Researchers are excited about this approach because it could potentially reduce the duration of treatment, minimizing side effects while maintaining effectiveness. For postmenopausal women, the focus is on initial therapy with aromatase inhibitors, but Tamoxifen is used if there are contraindications. The flexibility in treatment options based on menopausal status and contraindications offers a tailored approach that could improve patient outcomes and quality of life.

What evidence suggests that this treatment might be an effective treatment for breast cancer?

Research has shown that tamoxifen effectively lowers the risk of breast cancer. Women who took tamoxifen for five years had a 17% lower chance of cancer recurrence and a 9% lower risk of dying from breast cancer. The treatment also reduced the chance of developing a new breast cancer in the other breast by 75%. Tamoxifen decreased the rate of estrogen receptor-positive breast cancer by 69%. In this trial, tamoxifen is part of the standard of care endocrine therapy for certain participants, highlighting its potential as a strong option for women with hormone receptor-positive breast cancer, especially in preventing recurrence or new development. ^{2 5 6 7 8}

Who Is on the Research Team?

Caroline Lohrisch, MC

Principal Investigator

BC Cancer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9938251/

Tamoxifen evolution - PMC Tamoxifen 5 mg also reduced contralateral breast cancer by 75% (3 vs 12 events P = .02) [45]. The 5 mg dose of tamoxifen (named 'baby-TAM' by ...

2. cancer.gov cancer.gov/types/breast/research/tamoxifen-15-year-benefits

Five Years of Tamoxifen Continues to Benefit Women 15 ... Women who took tamoxifen for 5 years had a 17 percent lower risk of cancer recurrence and a 9 percent lower risk of death from breast cancer ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0960977623005337

Breast cancer survival and incidence of second primary ... Three more years of tamoxifen therapy reduced the risk of breast cancer mortality. The difference was established during the first 15 years after randomization.

4. academic.oup.com academic.oup.com/jnci/article/90/18/1371/897928

Tamoxifen for Prevention of Breast Cancer: Report of the ... The annual rate of estrogen receptor (ER)-positive breast cancers was 69% less in women in the tamoxifen group. The rates were 5.02 per 1000 women in the ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01342

Reassessing the Benefits and Harms of Risk-Reducing ... Risk-reducing tamoxifen with annual screening (± MRI) decreased the risk of invasive breast cancer by 40% and breast cancer death by 57%, compared with no ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK532905/

Tamoxifen - StatPearls - NCBI Bookshelf - NIH Patient- versus physician-reported outcomes in a low-dose tamoxifen trial in noninvasive breast cancer. Breast J. 2021 Nov;27(11):817-823 ...

7. nature.com nature.com/articles/s41416-023-02158-5

Tamoxifen evolution | British Journal of Cancer The ATTOM trial randomised 6,953 patients with ER-positive early breast cancer to the same approach and showed improved outcome with longer ...

8. cancer.gov cancer.gov/types/breast/research/tamoxifen-long-lasting-benefit

Long-Term Data from 20 Trials Confirm Tamoxifen's ... Women who took tamoxifen also had a one-third reduction in the risk of dying from breast cancer throughout the 15-year follow-up period. Source.