Endocrine Therapy Before Surgery for Early-Stage Breast Cancer

(POWER Trial)

Recruiting at 1 trial location

Overseen By Amy B Smith

Age: 65+

Sex: Female

Trial Phase: Phase 2

Sponsor: Trish Millard, MD

Must be taking: Endocrine therapy

Must not be taking: Strong CYP2D6 inhibitors

Disqualifiers: Prior endocrine therapy, Pregnancy, others

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

83 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if giving hormone therapy helps older women with early-stage breast cancer tolerate the treatment and decide if they can skip radiation. The therapy works by blocking estrogen, which some breast cancers need to grow.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use strong CYP2D6 inhibitors like Fluoxetine or Paroxetine during the study.

What evidence supports the effectiveness of the drug treatment for early-stage breast cancer?

Research shows that using endocrine therapy, like aromatase inhibitors (letrozole, anastrozole, exemestane) and tamoxifen, before surgery can shrink tumors in patients with estrogen receptor-positive breast cancer, making surgery easier and more effective. These drugs have been found to be well-tolerated and can lead to more breast-conserving surgeries compared to other treatments. ^{1 2 3 4 5}

Is endocrine therapy before surgery for early-stage breast cancer safe?

Tamoxifen and aromatase inhibitors like letrozole, anastrozole, and exemestane are generally considered safe for treating breast cancer, but they can have side effects. Tamoxifen may increase the risk of blood clots and uterine cancer, while aromatase inhibitors are usually better tolerated with fewer serious side effects. ^{6 7 8 9 10}

How is the drug Tamoxifen/Letrozole/Anastrozole/Exemestane unique for early-stage breast cancer treatment?

This drug combination is unique because it is used as a pre-surgery treatment to shrink tumors in estrogen receptor-positive breast cancer, allowing for less invasive surgery. Unlike chemotherapy, it has fewer side effects and can be continued around the time of surgery, with newer aromatase inhibitors like letrozole and anastrozole showing better response rates than tamoxifen. ^{1 2 4 5 11}

Research Team

Shayna L. Showalter

Principal Investigator

University of Virginia

Eligibility Criteria

This trial is for women aged 65 or older with early-stage, hormone receptor-positive breast cancer. Participants must have a tumor size ≤ 2 cm, be able to take oral medication, and commit to pre-surgery endocrine therapy for three months. They should not have used endocrine therapy before, be pregnant or breastfeeding, or require treatment for another progressing malignancy.

Inclusion Criteria

I can take pills and will follow hormone therapy for 3 months before surgery.

I can take care of myself and perform daily activities.

I have chosen breast-conserving surgery.

Exclusion Criteria

I have another cancer besides the one being studied, but it's not getting worse or needing treatment, except for certain skin cancers or cervical cancer that's been treated.

I have used hormone therapy for breast cancer.

I have had radiation therapy on the same side of my breast before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Endocrine Therapy

Participants receive 3 months of pre-operative endocrine therapy to assess tolerance and inform radiation therapy decisions

12 weeks

Regular visits for patient-reported outcome measures

Surgery and Decision-making

Participants undergo breast conservation surgery and make decisions regarding radiation therapy based on tolerance to endocrine therapy

Up to 90 days post-surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including quality of life and symptom burden assessments

24 months

Treatment Details

Interventions

• Patient Reported Outcomes
• Tamoxifen/Letrozole/Anastrozole/Exemestane

Trial Overview The study tests the tolerance of older women with breast cancer to pre-operative endocrine therapies like tamoxifen, letrozole, anastrozole, or exemestane over three months. Patient surveys will measure how well they tolerate the drugs before surgery.

Participant Groups

Group I: Pre-operative endocrine therapy Experimental Treatment 2 Interventions

All participants enrolled to the study will receive 3 months of pre-operative endocrine therapy (e.g. tamoxifen or aromatase inhibitors (AIs) such as letrozole, anastrozole, or exemestane). The choice and dose of endocrine therapy will be at the discretion of the treating medical oncologist.

Who Is Running the Clinical Trial?

Trish Millard, MD

Lead Sponsor

Trials

1

Recruited

80+

Shayna Showalter, MD

Lead Sponsor

Trials

3

Recruited

470+

Findings from Research

Neoadjuvant endocrine therapy using aromatase inhibitors has shown greater success than tamoxifen in reducing tumor volume in postmenopausal women with estrogen receptor-positive breast cancer, allowing for more surgical options.

The effectiveness of neoadjuvant therapy is linked to estrogen receptor expression levels, with higher expression correlating with better responses and tumor shrinkage, and early research suggests that reduced cell proliferation after 14 days of treatment may serve as a biomarker for response to tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of endocrine therapy in the neoadjuvant surgical setting. Dixon, JM.[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]

Endocrine therapy, particularly with tamoxifen and newer agents like aromatase inhibitors, is effective for treating hormone-sensitive breast cancer, providing a more tolerable treatment option for patients.

Neoadjuvant endocrine therapy is gaining recognition for its potential benefits in treating initially inoperable locally advanced breast cancers, with clinical assessments helping predict future treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neoadjuvant endocrine therapy for breast cancer: an overview]. Domont, J., Namer, M., Khayat, D., et al.[2018]

Preoperative endocrine therapy for ER-positive breast cancer can achieve a response rate of nearly 70% within about 3 months, offering a less toxic alternative to neoadjuvant chemotherapy, which has no demonstrated survival benefit over adjuvant therapy.

Further randomized clinical trials are needed to establish the effectiveness of preoperative endocrine therapy compared to traditional adjuvant therapy, determine the optimal treatment duration, and identify additional predictive factors for patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative endocrine therapy for breast cancer. Cheung, KL., Howell, A., Robertson, JF.[2019]

Tamoxifen has been shown to reduce breast cancer incidence by 30-40%, but it carries risks such as endometrial cancer and blood clots, prompting the exploration of safer alternatives like raloxifene and lower doses of tamoxifen.

New strategies, including the combination of hormone replacement therapy with tamoxifen and the investigation of anastrozole, aim to enhance the benefits of breast cancer prevention while minimizing risks, especially for women at higher risk of estrogen receptor-positive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in chemoprevention of breast cancer. Serrano, D., Perego, E., Costa, A., et al.[2015]

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 study of 337 postmenopausal women with ER and/or PgR positive breast cancer, letrozole demonstrated a significantly higher overall objective response rate (55%) compared to tamoxifen (36%) after four months of treatment.

Letrozole also showed superior results in secondary endpoints, including ultrasound response (35% vs. 25%) and mammographic response (34% vs. 16%), while both treatments were well tolerated, indicating letrozole's effectiveness as a preoperative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Eiermann, W., Paepke, S., Appfelstaedt, J., et al.[2022]

The NCIC-CTG MA.17/BIG 1-97 trial demonstrated that extending endocrine therapy with letrozole after five years of tamoxifen significantly improves disease-free survival in hormone-receptor-positive early breast cancer patients, leading to the trial's early termination due to positive results.

This study particularly highlighted the benefits of letrozole for women with node-positive disease and pre-menopausal status, establishing it as a key approach for extended adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial. Higgins, MJ., Liedke, PE., Goss, PE.[2022]

Letrozole, a third-generation aromatase inhibitor, has emerged as a significant advancement in hormonal therapy for postmenopausal women with hormone-sensitive early breast cancer, showing improved efficacy compared to the traditional treatment with Tamoxifen.

Recent trials indicate that letrozole offers distinct pharmacokinetic and pharmacodynamic advantages, along with a different side effect profile, which may enhance treatment outcomes for patients compared to other hormonal agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: present and future role in the treatment of breast cancer. Amar, S., Roy, V., Perez, EA.[2019]

Pre-operative endocrine therapy is now recognized as a valuable treatment option for postmenopausal women with estrogen receptor-positive (ER+) breast cancer, helping to down-stage large or locally advanced tumors before surgery.

Recent advancements include the use of dual endocrine targeting and combinations with other targeted therapies, which may improve long-term outcomes and provide important prognostic information for managing ER+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-operative Endocrine Therapy. Arthur, LM., Turnbull, AK., Khan, LR., et al.[2022]

References

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

Role of endocrine therapy in the neoadjuvant surgical setting. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Neoadjuvant endocrine therapy in breast cancer. [2022]

3. France pubmed.ncbi.nlm.nih.gov

[Neoadjuvant endocrine therapy for breast cancer: an overview]. [2018]

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

Preoperative endocrine therapy for breast cancer. [2019]

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

The scientific value of preoperative studies and how they can be used. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Progress in chemoprevention of breast cancer. [2015]

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

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

8. England pubmed.ncbi.nlm.nih.gov

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. [2022]

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

Extended adjuvant endocrine therapy in hormone dependent breast cancer: the paradigm of the NCIC-CTG MA.17/BIG 1-97 trial. [2022]

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

Letrozole: present and future role in the treatment of breast cancer. [2019]

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

Pre-operative Endocrine Therapy. [2022]