Endocrine Therapy for Low-Risk Breast Cancer

Recruiting at 2 trial locations

Overseen By Rebecca L Aft, M.D., Ph.D.

Age: 65+

Sex: Female

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Endocrine therapy

Must not be taking: Antiretrovirals

Disqualifiers: Prior surgery, Other malignancy, 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: 3

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether endocrine therapy alone can effectively control breast cancer in women aged 70 and older. It targets a specific group with tumors that have a good prognosis and are estrogen receptor-positive, meaning the cancer grows in response to estrogen. The trial explores treatments like anastrozole, exemestane, fulvestrant, goserelin, and tamoxifen. Women recently diagnosed with certain types of breast cancer that haven't spread much and have specific tumor characteristics might be suitable for this study. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to advancements in breast cancer treatment.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments in this trial have been used successfully in other contexts. Anastrozole, for instance, often treats early-stage hormone receptor-positive breast cancer and is generally well-tolerated, with common side effects like mild hot flashes. Exemestane is considered safe and more effective than tamoxifen, with fewer side effects. Fulvestrant treats advanced breast cancer and is generally safe, though it can cause more side effects when combined with certain other medications.

Goserelin is approved for women with advanced breast cancer and is generally safe, though it may cause hot flashes and decreased sex drive. Tamoxifen is widely used for breast cancer and is safe for most people, though it can cause hot flashes and other mild side effects.

Past studies have shown each of these treatments to be safe, but individual experiences can vary. Always discuss potential side effects with your doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these endocrine therapies for low-risk breast cancer because they offer a more targeted approach with potentially fewer side effects compared to traditional chemotherapy. These treatments, such as anastrozole, exemestane, and tamoxifen, work by blocking hormones that fuel cancer growth, which is a different strategy than the aggressive cell-killing action of chemotherapy. Additionally, the use of the Oncotype DX assay to predict recurrence risk and tailor treatment is a personalized approach, helping to avoid unnecessary treatments for those who may not need them. This approach not only targets the cancer more precisely but also aims to improve patients' quality of life by reducing exposure to the harsh effects of chemotherapy.

What evidence suggests that this trial's treatments could be effective for low-risk breast cancer?

In this trial, participants will receive endocrine therapy alone, which may include treatments such as anastrozole, exemestane, fulvestrant, goserelin, or tamoxifen. Research has shown that certain hormone therapies, like anastrozole and exemestane, can significantly lower the chance of breast cancer recurrence. Anastrozole reduces the return of the disease by 41% and breast cancer-related deaths by 34%. Exemestane lowers the risk of recurrence or death by 24% compared to tamoxifen and reduces new invasive breast cancers by 65% in women at high risk. Fulvestrant has been effective in delaying disease progression, with some studies showing benefits lasting over 16 months. Goserelin works as well as other treatments in managing breast cancer. Tamoxifen has a long track record of reducing breast cancer deaths and is effective in both early and advanced stages. These treatments target estrogen, a hormone that can help certain breast cancers grow, making them effective for estrogen receptor-positive (ER+) breast cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Rebecca L Aft, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for women aged 70 or older with a specific type of breast cancer that's sensitive to hormones and hasn't spread widely (ER+ operable invasive breast cancer, cT1 or T2, N0-1, M0). Participants should have low levels of a protein called Ki67, be able to perform daily activities with some limitations (ECOG ≤ 3), and not have had previous surgery for this cancer. Women with HIV on antiretroviral therapy, other recent cancers, or severe illnesses are excluded.

Inclusion Criteria

I am capable of only limited self-care, confined to my bed or chair more than 50% of waking hours.

My cancer is estrogen receptor positive and HER2 negative.

Your Ki67 score, which shows how fast cells are growing, is less than or equal to 30%, or you have a low to intermediate mitotic index.

Exclusion Criteria

Uncontrolled intercurrent illness as determined by their treating physician which would limit compliance with study requirements

You have had allergic reactions to similar medicines or substances like the ones used in the study.

I have had surgery for my cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Endocrine Therapy

Participants receive neoadjuvant endocrine therapy, including options like goserelin, anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen, with office visits every 3 to 6 months for tumor assessment.

12 months

Office visits every 3 to 6 months

Follow-up

Participants are monitored for response and progression using RECIST criteria, and quality of life is assessed at baseline, Year 1, and Year 2.

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Exemestane
• Fulvestrant
• Goserelin
• Tamoxifen

Trial Overview

The study tests if endocrine therapy alone can control breast cancer in elderly women without the need for surgery. It involves treatments like Fulvestrant, Tamoxifen, Anastrozole, Exemestane and Goserelin. The effectiveness will be measured by changes in tumor size using ultrasound or mammogram and quality of life assessments.

How Is the Trial Designed?

Group I: Endocrine therapy alone Experimental Treatment 7 Interventions

* Neoadjuvant endocrine therapy will be given at the discretion of the treating physician as directed by the package insert and could include the following: goserelin, anastrozole, letrozole, exemestane, fulvestrant, or tamoxifen * Frequency of office visits will be decided by the treating physician but must occur no less frequently than every 3 to 6 months for tumor assessment * After 6 months and after 12 months, patients will be assessed; patients who progress will have standard care recommended , and at any point a patient can opt to receive standard care even if she has not progressed on neoadjuvant endocrine therapy * Information on quality of life will be collected at baseline, Year 1, and Year 2 by the FACT-B questionnaire * Archival tissue will be collected and sent to Genomic Health for analysis using the Oncotype DX assay. The Recurrence Score predicts chemotherapy benefit and indicates the 10-year risk of recurrence (will not be used to determine treatment)

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Genomic Health®, Inc.

Industry Sponsor

Trials

15

Recruited

5,300+

Published Research Related to This Trial

Aromatase inhibitors (AIs) provide a significant survival benefit for postmenopausal women with advanced breast cancer compared to other endocrine therapies, with a pooled hazard ratio of 0.90 based on 31 trials involving 11,403 women.

AIs have a different toxicity profile than other endocrine treatments, showing similar rates of hot flushes and arthralgia, but significantly lower risks of vaginal bleeding (71% decrease) and thromboembolic events (47% decrease).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Gibson, L., Lawrence, D., Dawson, C., et al.[2022]

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, 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]

Neoadjuvant endocrine therapy, particularly with aromatase inhibitors like letrozole, anastrozole, and exemestane, is proving to be a safe and effective alternative to chemotherapy for certain breast cancer patients.

This therapy can help convert inoperable breast tumors to operable ones, allowing for less invasive surgical options, and also provides a chance to study the biological effects of these treatments on tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant use of endocrine therapy in breast cancer. Macaskill, EJ., Dixon, JM.[2022]

New endocrine therapies, such as aromatase inhibitors (anastrozole, letrozole, exemestane) and fulvestrant, show superior efficacy and tolerability compared to the traditional treatment tamoxifen for postmenopausal women with advanced breast cancer.

Sequential use of these newer agents can prolong the effectiveness of endocrine therapies while minimizing the acute toxicities associated with cytotoxic chemotherapy, making them a valuable option in palliative care for advanced breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen--what next? Gradishar, WJ.[2019]

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 retrospective analysis of the ATAC trial, women taking tamoxifen experienced significantly more gynecologic adverse events (34.2%) compared to those taking anastrozole (20.5%), leading to more medical interventions, including a nearly fourfold increase in hysterectomies.

The findings support the use of anastrozole as the preferred initial treatment for early hormone receptor-positive breast cancer due to its lower incidence of gynecologic complications, particularly since most adverse events with tamoxifen occurred within the first 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. Duffy, SR., Distler, W., Howell, A., et al.[2018]

Third-generation aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane have emerged as effective alternatives to tamoxifen for treating postmenopausal breast cancer, particularly in hormone receptor-positive cases, as shown in the ATAC trial with over five years of follow-up.

Fulvestrant, a new type of estrogen receptor antagonist with no partial agonist activity, represents a promising option in breast cancer treatment, and the review discusses future sequencing strategies for using AIs earlier in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of postmenopausal breast cancer. Howell, A.[2018]

In a study of 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

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]

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