Endocrine Therapy for Older Patients with Breast Cancer

Recruiting at 6 trial locations

Overseen By Marta Sienkiewicz, MSc

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Hospital Research Institute

Disqualifiers: Metastatic cancer

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 24

Duration: 5 years

109 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if older women (70+) with low-risk early breast cancer can safely skip hormone-blocking treatment. The goal is to see if they can avoid the side effects of this treatment without increasing the risk of cancer returning.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of endocrine therapy for older patients with breast cancer?

Endocrine therapy, including drugs like tamoxifen and aromatase inhibitors (such as anastrozole, letrozole, and exemestane), is effective for older patients with breast cancer because it can control the disease and reduce the need for extensive surgery. Aromatase inhibitors are particularly beneficial for postmenopausal women, offering better outcomes than tamoxifen with fewer side effects. ^{1 2 3 4 5}

Is endocrine therapy safe for older patients with breast cancer?

Endocrine therapy, including drugs like tamoxifen and aromatase inhibitors (anastrozole, letrozole, exemestane), is generally considered safe for older patients with breast cancer. It has fewer toxicities compared to chemotherapy, but may cause side effects like bone fractures and joint pain. Overall, it is well-tolerated when used appropriately. ^{1 5 6 7 8}

How is endocrine therapy unique for treating older patients with breast cancer?

Endocrine therapy is unique for older patients with breast cancer because it offers effective treatment with fewer side effects compared to chemotherapy, making it suitable for those with other health issues. It uses drugs like aromatase inhibitors, which are particularly effective in postmenopausal women, to control the disease and reduce the need for extensive surgery. ^{1 2 5 9 10}

Research Team

Marie-France Savard

Principal Investigator

Ottawa Hospital Research Institute

Eligibility Criteria

This trial is for patients aged 70 or older with early-stage, lower-risk hormone receptor-positive breast cancer. They must be able to consent and fill out questionnaires in French or English, have a new diagnosis of certain types of breast carcinoma, and have undergone specific surgeries without metastatic cancer.

Inclusion Criteria

My tumor is small and varies in aggressiveness based on its size.

I can give my consent and answer questions in English or French.

My breast cancer is ER+ and/or PR+, and HER2-.

Exclusion Criteria

My cancer has spread to other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either the omission of endocrine therapy or administration of endocrine therapy for at least 5 years

5 years

Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years, and 5 years

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

5 years

Baseline, 12 weeks, 26 weeks, 1 year, 2 years, 3 years, 4 years, and 5 years

Treatment Details

Interventions

• Endocrine therapy
• No endocrine therapy

Trial Overview The study is testing the necessity of endocrine therapy (ET) after surgery in older patients with low-risk breast cancer. It randomly assigns participants to either receive ET or no ET post-surgery to see if omitting ET can still effectively manage their condition.

Participant Groups

Group I: Omission of endocrine therapy Experimental Treatment 1 Intervention

Omission of endocrine therapy

Group II: Administration of endocrine therapy for at least 5 years Active Control 1 Intervention

Administration of endocrine therapy for at least 5 years

Endocrine therapy is already approved in United States, European Union for the following indications:

Approved in United States as Tamoxifen for:

• Adjuvant treatment of ER-positive early-stage breast cancer
• Treatment of metastatic breast cancer
• Risk reduction of breast cancer in high-risk women

Approved in United States as Anastrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Letrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Exemestane for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in United States as Fulvestrant for:

• Treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer
• Treatment of postmenopausal women with HR-positive advanced breast cancer with disease progression on endocrine therapy

Approved in United States as Elacestrant for:

• Treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy

Approved in European Union as Tamoxifen for:

• Adjuvant treatment of ER-positive early-stage breast cancer
• Treatment of metastatic breast cancer
• Risk reduction of breast cancer in high-risk women

Approved in European Union as Anastrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Letrozole for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Exemestane for:

• Adjuvant treatment of postmenopausal women with ER-positive early-stage breast cancer
• Treatment of postmenopausal women with advanced breast cancer

Approved in European Union as Fulvestrant for:

• Treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer
• Treatment of postmenopausal women with HR-positive advanced breast cancer with disease progression on endocrine therapy

Approved in European Union as Elacestrant for:

• Treatment of postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

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]

A longitudinal study from 2001 to 2012 across nine developed countries showed a significant shift in breast cancer treatment from tamoxifen to aromatase inhibitors, with aromatase inhibitors making up over half of total endocrine therapy use by 2012.

The study found that while tamoxifen use stabilized or slightly increased, the overall trend towards aromatase inhibitors aligns with clinical guidelines recommending their use for post-menopausal women, indicating a change in treatment practices based on evolving evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal trends in utilization of endocrine therapies for breast cancer: an international comparison. Kelly, E., Lu, CY., Albertini, S., et al.[2022]

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]

In a study of 3887 post-menopausal patients with hormone receptor-positive early breast cancer, over 85% persisted with letrozole treatment for 12 months, but 14.6% discontinued, primarily due to side effects.

Musculoskeletal symptoms and sleep disorders were the most significant adverse events leading to treatment discontinuation, with hazard ratios of 2.55 and 1.95, respectively, indicating a strong need for targeted compliance programs to support patients experiencing these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study. Nabieva, N., Fehm, T., Häberle, L., et al.[2022]

Aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane are effective adjuvant therapies for postmenopausal women with hormone receptor-positive invasive breast cancer, showing similar overall survival rates compared to tamoxifen.

While AIs have acceptable toxicity profiles with fewer endometrial cancers and thromboembolic events, they are associated with a higher risk of bone fractures and joint pain compared to tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations. Carlson, RW., Hudis, CA., Pritchard, KI.[2019]

Endocrine therapy is a key treatment for metastatic breast cancer, offering effective and minimally toxic options, with tamoxifen being the preferred first-line therapy for both premenopausal and postmenopausal women.

Research is ongoing to develop new 'pure' antiestrogens and to combine endocrine therapy with biologic agents, which may enhance treatment effectiveness in both early and advanced stages of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy in metastatic breast cancer. Kimmick, GG., Muss, HB.[2019]

References

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

Current Strategies of Endocrine Therapy in Elderly Patients with Breast Cancer. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant use of hormonal therapy in elderly patients with early or locally advanced hormone receptor-positive breast cancer. [2018]

3. Lebanon pubmed.ncbi.nlm.nih.gov

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

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

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

5. England pubmed.ncbi.nlm.nih.gov

Longitudinal trends in utilization of endocrine therapies for breast cancer: an international comparison. [2022]

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

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

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

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study. [2022]

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

Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

Recent perspectives of endocrine therapy for breast cancer. [2019]

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

Endocrine therapy in metastatic breast cancer. [2019]