Endocrine Therapy for Low-Risk Breast Cancer

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

Age: 65+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing if hormone therapy alone can effectively treat breast cancer in women aged 70 or older with certain types of tumors. The therapy works by blocking estrogen, which helps stop cancer cells from growing. Researchers believe this approach could be enough to control the cancer without needing more aggressive treatments.

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.

What data supports the effectiveness of the drug Anastrozole for low-risk breast cancer?

Research shows that aromatase inhibitors like Anastrozole are more effective and have better tolerability than Tamoxifen for treating hormone-sensitive early breast cancer in postmenopausal women. ^{1 2 3 4 5}

Is endocrine therapy for low-risk breast cancer safe?

Research shows that newer endocrine therapies like anastrozole, letrozole, and exemestane are generally well-tolerated and have fewer side effects compared to tamoxifen, which has been used for many years. These treatments have been shown to be safe for postmenopausal women with hormone-sensitive breast cancer. ^{1 2 3 6 7}

How is the drug Anastrozole, Exemestane, Fulvestrant, Goserelin, Tamoxifen unique for low-risk breast cancer?

This drug combination is unique because it uses a mix of aromatase inhibitors (which block estrogen production) and selective estrogen receptor modulators (which block estrogen's effects) to treat low-risk breast cancer, offering an alternative to chemotherapy with potentially fewer side effects. ^{1 5 8 9 10}

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Anastrozole (Hormone Therapy)
• Exemestane (Hormone Therapy)
• Fulvestrant (Hormone Therapy)
• Goserelin (Hormone Therapy)
• Tamoxifen (Hormone Therapy)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 (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]

References

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

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

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

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

3. England pubmed.ncbi.nlm.nih.gov

Tamoxifen--what next? [2019]

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

Aromatase inhibitors in breast cancer: an update. [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

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. [2018]

7. England 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. [2022]

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

Neoadjuvant use of endocrine therapy in breast cancer. [2022]

9. Lebanon pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. [2022]