Neoadjuvant Endocrine Therapy for Breast Cancer

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the optimal duration of hormone-blocking therapy before surgery to effectively treat breast cancer. It seeks to determine how cancer responds to varying treatment durations and to predict a specific tumor score that guides treatment. Participants include those with early-stage breast cancer (Stage I-III) eligible for hormone-blocking therapy before surgery. The trial consists of three groups with treatment lengths ranging from less than 8 weeks to up to a year. Individuals diagnosed with early-stage breast cancer and scheduled for surgery may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to significant findings in breast cancer treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that neoadjuvant endocrine therapy (NET) is generally safe for breast cancer patients. Studies have found that NET has low toxicity, meaning it usually doesn't cause severe side effects, and most patients handle it well. Additionally, NET can effectively treat localized estrogen receptor-positive (ER+) breast cancer, a common type where cancer cells grow due to the hormone estrogen.

Besides being well-tolerated, NET is linked to better surgical outcomes. For example, patients who receive NET often have a lower chance of needing a mastectomy (breast removal surgery) compared to those who undergo surgery without prior treatment.

In summary, research suggests that NET is a safe and effective option for treating certain types of breast cancer. It's always important to discuss any potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about Neoadjuvant Endocrine Therapy (NET) for breast cancer because it offers a tailored approach based on treatment duration, potentially enhancing patient outcomes. Unlike traditional chemotherapy, which can be harsh and has a systemic effect, NET specifically targets hormone receptors, which can mean fewer side effects and a more focused treatment. The trial explores three duration strategies: short (up to 8 weeks), intermediate (more than 8 weeks but up to 24 weeks), and extended (more than 24 weeks but up to 52 weeks), allowing researchers to determine the most effective treatment length. This approach not only personalizes therapy but also aims to optimize the balance between treatment efficacy and quality of life for patients.

What evidence suggests that Neoadjuvant Endocrine Therapy could be effective for breast cancer?

Research has shown that neoadjuvant endocrine therapy (NET), a hormone-blocking treatment given before surgery, can be effective for early-stage breast cancer. One study found that patients experienced an average tumor reduction of 66% after three months, with nearly 92% showing improvement. NET has also been linked to a lower likelihood of requiring a mastectomy, compared to immediate surgery. Although the complete response rate was 11% in lymph nodes and 1.6% in the breast, these findings suggest that NET can shrink tumors and reduce the need for more invasive surgeries. This trial will evaluate different durations of NET, assigning participants to short, intermediate, or extended duration treatment arms. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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 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, 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]

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, 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 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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7554166/

How Effective Is Neoadjuvant Endocrine Therapy (NET) in ...

With NET, the nodal pCR rate was 4/38 (11%) of biopsy-proven cases, and the breast pCR rate was 2/126 (1.6%). Nodal-downstaging rates with NET and NAC were not ...

2.

academic.oup.com

academic.oup.com/bjsopen/article/8/5/zrae100/7826552

Surgical outcomes of neoadjuvant endocrine treatment in ...

Overall, neoadjuvant endocrine therapy was associated with a lower mastectomy rate compared with surgery first (risk ratio (RR) 0.53, 95% c.i. ...

3.

asco.org

asco.org/abstracts-presentations/ABSTRACT190141

Comparing outcomes of neoadjuvant endocrine therapy ...

Results: A total of 154 patients met eligibility criteria for this study. One hundred and six patients (69%) received NACT and 48 (31%) received NET. Women ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S1040842822003249

Neoadjuvant endocrine therapy for luminal breast tumors

Noteworthy, a single arm study confined to ILC showed a mean reduction in tumor volume at 3 months of 66%, with a clinical response rate of almost 92% with ...

5.

jamanetwork.com

jamanetwork.com/journals/jamaoncology/fullarticle/2804892

Efficacy of Endocrine Therapy Plus Trastuzumab and ...

This randomized clinical trial aims to determine whether neoadjuvant de-escalated chemotherapy is superior to endocrine therapy, ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5738656/

Neoadjuvant Endocrine Therapy for Estrogen Receptor ...

Conclusions. Neoadjuvant endocrine therapy can be a safe and effective option for localized ER+ breast cancer. Given the low toxicity associated with NET, ...

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S0960977624000572

Radiological, pathological and surgical outcomes after ...

This study aims to evaluate the response to and surgical outcomes following NET in clinical high risk ER+/HER2-breast cancer patients with a genomic low risk ...

8.

frontiersin.org

frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1420214/full

Efficacy and safety of different regimens of neoadjuvant ...

Conclusions: The CT(A)+Olaparib and CT(A)+nivolumab groups demonstrated superior efficacy in neoadjuvant therapy for HR+/HER2- breast cancer.

9.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.20.03399

Neoadjuvant Chemotherapy, Endocrine Therapy, and ...

ASCO convened an Expert Panel to conduct a systematic review of the literature on neoadjuvant therapy for breast cancer and provide recommended care options.