Neoadjuvant Endocrine Therapy for Breast Cancer

Overseen By Pavani Chalasani, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: George Washington University

Must be taking: Endocrine therapy

Disqualifiers: Inability to comply, 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: Unknown

Duration: 2 weeks to 1 year

90 Participants Needed

Trial Summary

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 the treatment Neoadjuvant Endocrine Therapy for Breast Cancer?

Neoadjuvant endocrine therapy is effective in improving surgical outcomes for postmenopausal women with hormone receptor-positive breast cancer, allowing for more breast-conserving surgeries. Studies show that newer drugs like letrozole, anastrozole, and exemestane are more effective than tamoxifen, leading to higher response rates and better surgical options. ^{1 2 3 4 5}

Is neoadjuvant endocrine therapy for breast cancer safe?

Neoadjuvant endocrine therapy, which includes treatments like tamoxifen and aromatase inhibitors (letrozole, anastrozole, exemestane), is generally well tolerated and considered safe for breast cancer patients, with few patients needing to stop treatment due to side effects. ^{5 6 7 8 9}

How is neoadjuvant endocrine therapy different from other breast cancer treatments?

Neoadjuvant endocrine therapy is unique because it is used before surgery to shrink hormone receptor-positive breast tumors, making them operable or allowing for breast-conserving surgery instead of mastectomy. It is particularly effective in postmenopausal women and uses drugs like aromatase inhibitors (letrozole, anastrozole, exemestane) which have shown better outcomes compared to tamoxifen, offering a non-chemotherapy option with fewer side effects. ^{1 3 4 5 6}

What is the purpose of this trial?

The goal of this clinical trial is to determine how the duration of hormone blocking (endocrine) therapy given prior to surgery (called "neoadjuvant" treatment) affects breast cancer. The main questions the trial aims is answer are: 1. How breast cancer responds to endocrine therapy given prior to surgery? 2. To predict tumor pre-operative endocrine prognostic index (PEPI) score for subjects enrolled in cohort B or C Participants with early-stage breast cancer (Stage I-III) who are eligible for Neoadjuvant Endocrine Therapy (NET) will be enrolled in the study. Participants will: * receive endocrine therapy as part of regular care for breast cancer * consent to samples of blood and tissue evaluation to determine how endocrine therapy effects the tumor * participate in this research anywhere from 2 weeks to 1 year, depending on duration of endocrine therapy and when surgery will be performed

Eligibility Criteria

This trial is for individuals with early-stage breast cancer (Stage I-III) who are candidates for hormone-blocking therapy before surgery. Participants will receive standard endocrine therapy, provide blood and tissue samples, and may be involved in the study from 2 weeks to a year.

Inclusion Criteria

I am eligible for surgery to remove my cancer.

Be willing and able to comply with scheduled visits, treatment plan, and follow up with research staff

I understand this study is experimental and I know what it involves.

Exclusion Criteria

Inability to comply taking NET

Inability to comply to study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant endocrine therapy (NET) for breast cancer, with duration varying by cohort: up to 8 weeks for Cohort A, 8-24 weeks for Cohort B, and 24-52 weeks for Cohort C.

2 weeks to 1 year

Follow-up

Participants are monitored for response to endocrine therapy and prediction of PEPI score and Ki67 levels post-surgery.

4 weeks

Treatment Details

Interventions

• Neoadjuvant Endocrine Therapy

Trial Overview The study investigates how different durations of neoadjuvant endocrine therapy affect breast cancer response prior to surgery. It also aims to predict the tumor's pre-operative prognostic index based on this treatment.

Participant Groups

Group I: Cohort A: Short Duration NET Active Control 1 Intervention

Patients in this cohort can be treated with NET up to 8weeks (\<= 8 weeks)

Group II: Cohort B: Intermediate Duration NET Active Control 1 Intervention

Patients in this cohort can be treated with NET \> 8weeks but \<=24 weeks

Group III: Cohort C: Extended Duration NET Active Control 1 Intervention

Patients in this cohort can be treated with NET \>24 weeks but \<= 52 weeks

Who Is Running the Clinical Trial?

George Washington University

Lead Sponsor

Trials

263

Recruited

476,000+

Findings from Research

Neoadjuvant endocrine therapy is becoming a preferred treatment for operable estrogen receptor-positive (ER+) breast cancer, offering an effective alternative to chemotherapy.

Understanding the mechanisms behind both primary and acquired resistance to endocrine therapy is crucial for improving treatment strategies and developing new drugs targeting ER+ breast cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of neoadjuvant endocrine therapy. Agrawal, LS., Mayer, IA.[2021]

Neoadjuvant endocrine therapy is being used more frequently to enhance surgical options for postmenopausal women with large hormone receptor-positive breast cancer, suggesting its growing importance in treatment planning.

Recent studies indicate that the tumor response to this therapy may predict long-term outcomes for patients receiving subsequent adjuvant endocrine therapy, highlighting the potential benefits of broader application in hormone receptor-positive breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool. Chia, YH., Ellis, MJ., Ma, CX.[2022]

Neoadjuvant endocrine therapy is beneficial for postmenopausal women with bulky hormone receptor-positive breast cancer, leading to improved surgical outcomes.

This therapy may also be effective for smaller tumors, allowing for the identification of molecular predictors of response and potential combination treatments to enhance effectiveness and address endocrine resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant endocrine therapy for breast cancer. Chawla, JS., Ma, CX., Ellis, MJ.[2021]

Neoadjuvant endocrine therapy, particularly with third-generation aromatase inhibitors like letrozole, is effective in downstaging ER-rich breast cancers, allowing many initially inoperable tumors to become resectable, especially in postmenopausal women.

Letrozole has shown significantly higher response rates compared to tamoxifen in a large trial, leading to increased rates of successful breast-conserving surgeries and a low rate of local recurrence after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant endocrine therapy of breast cancer: a surgical perspective. Dixon, JM., Anderson, TJ., Miller, WR.[2022]

Neoadjuvant endocrine therapy, including tamoxifen and newer aromatase inhibitors, has shown to be effective and well tolerated in treating patients with hormone-sensitive breast cancer, offering better overall response rates compared to traditional tamoxifen treatment.

Patients with a higher estrogen receptor (ER) Allred score of 6 and above are more likely to benefit from neoadjuvant endocrine therapy, suggesting that this treatment could lead to more conservative surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant endocrine therapy in breast cancer. Abrial, C., Mouret-Reynier, MA., Curé, H., 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]

Neoadjuvant endocrine therapy, including tamoxifen and aromatase inhibitors, shows promise as an effective treatment for patients with hormone-sensitive breast cancer, particularly for elderly women with specific tumor characteristics.

This therapy is well tolerated compared to neoadjuvant chemotherapy, with fewer side effects leading to treatment discontinuation, and newer aromatase inhibitors demonstrate higher response rates than tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of neo-adjuvant hormonal therapy in the treatment of breast cancer: a review of clinical trials. Abrial, C., Durando, X., Mouret-Reynier, MA., et al.[2021]

In a study of 146 postmenopausal women with ER-positive/HER2-negative breast cancer, neoadjuvant endocrine therapy (NET) was found to be effective and safe, with no tumor progression during treatment and a majority undergoing successful breast-conserving surgery.

The study highlighted that 29.5% of patients achieved a low Preoperative Endocrine Prognostic Index (PEPI) score of 0, indicating favorable outcomes, suggesting that postmenopausal status and low-risk tumor characteristics should guide the selection of patients for NET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data on neoadjuvant endocrine therapy in ER-positive/HER2-negative breast cancer. da Silva, LR., de Andrade, CA., Brenelli, F., et al.[2021]

References

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

Optimizing the use of neoadjuvant endocrine therapy. [2021]

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

Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool. [2022]

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

Neoadjuvant endocrine therapy for breast cancer. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant endocrine therapy of breast cancer: a surgical perspective. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Neoadjuvant endocrine therapy in breast cancer. [2022]

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

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

7. Lebanon pubmed.ncbi.nlm.nih.gov

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Role of neo-adjuvant hormonal therapy in the treatment of breast cancer: a review of clinical trials. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Real-world data on neoadjuvant endocrine therapy in ER-positive/HER2-negative breast cancer. [2021]