Endocrine Therapy for Older Patients with Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether older patients with early-stage breast cancer can safely skip endocrine therapy (hormone therapy), typically prescribed for at least five years post-surgery. The goal is to determine if avoiding this treatment can prevent cancer recurrence without added side effects. Participants will either stop endocrine therapy or continue it to compare outcomes. This study targets patients aged 70 or older with a specific type of breast cancer treated with surgery and possibly radiotherapy, without lymph node involvement. As a Phase 4 trial, the research focuses on understanding how the already FDA-approved treatment can benefit more patients.

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 is the safety track record for endocrine therapy?

Research has shown that endocrine therapy is generally safe for people with breast cancer. Studies have found that taking tamoxifen, a common endocrine therapy, for 5 years can reduce the risk of cancer returning by 40% and lower the chance of dying from breast cancer by 30%. This suggests that most patients tolerate the treatment well.

Evidence also indicates that continuing endocrine therapy for up to 10 years is more effective at preventing cancer recurrence than stopping after 5 years. This extended treatment period has not been linked to major safety concerns, further supporting its safety.

While endocrine therapy can cause side effects like hot flashes or joint pain, it remains safe for most patients. This is why it is a standard treatment for breast cancer. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the approach of potentially omitting endocrine therapy for older patients with breast cancer because it could simplify treatment while maintaining effectiveness. Most treatments for breast cancer, like tamoxifen or aromatase inhibitors, involve extended endocrine therapy, which can have side effects like hot flashes, joint pain, and increased risk of other health issues over time. By evaluating whether the omission of this therapy is a viable option, this trial aims to determine if patients can avoid these side effects without compromising their cancer outcomes. If successful, this approach could lead to a less burdensome treatment path for older patients.

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

Research has shown that hormone therapy can lower the chance of breast cancer recurrence. One study found that tamoxifen, a common hormone therapy drug, reduced the annual death rate from breast cancer by 31% in women with hormone-sensitive breast cancer. Another large study demonstrated that taking hormone therapy for 5 years significantly lowered the risk of cancer returning over the next 15 years. Continuing hormone therapy for up to 10 years can further reduce the chance of recurrence compared to stopping after 5 years. In this trial, some participants will receive endocrine therapy for at least 5 years, while others will be in the group where endocrine therapy is omitted. These findings support the use of hormone therapy to manage early-stage breast cancer in older women. ^{2 3 6 7 8}

Who Is on the Research Team?

Marie-France Savard

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2722048/

An updated review on the efficacy of adjuvant endocrine ...

Adjuvant tamoxifen treatment has been associated with a 31% reduction in the annual breast cancer mortality rate among hormone receptor–positive women with ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S014067362501013X

patient-level meta-analysis of 12 randomised trials ...

In postmenopausal women with oestrogen receptor-positive early breast cancer, 5 years of adjuvant tamoxifen substantially reduces 15-year ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5764151/

Overall survival and progression-free ...

Fulvestrant 500 mg is the only endocrine therapy of those included in our review that showed improvements in both PFS/TTP and OS in both the first- and second- ...

4.

esmoopen.com

esmoopen.com/article/S2059-7029(25)00926-3/fulltext

Extended adjuvant endocrine therapy in early breast cancer

10 years of adjuvant ET is superior to 5 years in reducing recurrences. Seven to eight years of ET improves outcomes compared with 5 years.

5.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.24.00994

Final Overall Survival in the Phase III FALCON Trial

The randomized phase III FALCON trial demonstrated significant improvement in progression-free survival (PFS) with fulvestrant versus anastrozole in ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10453164/

Extended Adjuvant Endocrine Therapy in Early Breast ...

Taking tamoxifen for 5 years has been shown to reduce the risk of breast cancer recurrence by 40% and mortality by 30% compared to patients ...

7.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2212856

Interrupting Endocrine Therapy to Attempt Pregnancy after ...

In well-matched comparisons to an external control cohort, the POSITIVE trial showed no clear worsening of breast cancer outcomes in the short ...

8.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02308085

Study Details | NCT02308085 | Pregnancy Outcome and ...

For women desiring pregnancy after a breast cancer, 5-10 years of endocrine therapy may substantially reduce the chance of conception; however, a shorter ...