Endocrine Therapy Before Surgery for Early-Stage Breast Cancer

(POWER Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of endocrine therapy (hormone treatment) before surgery for women with early-stage estrogen receptor-positive breast cancer. The aim is to assess patient tolerance through self-reports. Participants will receive one of the following therapies for three months before surgery: tamoxifen or an aromatase inhibitor such as letrozole, anastrozole, or exemestane. Women who have chosen breast-conserving surgery, have a tumor size of 2 cm or smaller, and can take oral medication might be suitable for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that treatments like tamoxifen, letrozole, anastrozole, and exemestane have been thoroughly studied for safety in treating breast cancer. Studies have found that both anastrozole and tamoxifen lower the risk of breast cancer returning, though they cause different side effects.

Tamoxifen has been used for many years and is generally well-tolerated, with common side effects including hot flashes and a higher risk of blood clots. Aromatase inhibitors, such as letrozole, anastrozole, and exemestane, also treat breast cancer, especially in postmenopausal women, but can sometimes lead to bone thinning or a higher risk of fractures.

In studies comparing letrozole and anastrozole, the rates of serious side effects were similar, with only a small percentage of patients experiencing serious issues. Despite these risks, these treatments are widely used because they effectively control cancer.

Overall, while these treatments are considered safe, they do have side effects. Discussing with a doctor what to expect when taking these medications is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using endocrine therapy before surgery for early-stage breast cancer because it offers a tailored approach to shrinking tumors before they are removed. Unlike traditional methods that primarily focus on surgery first, this pre-operative endocrine therapy allows doctors to potentially reduce tumor size, making surgery less invasive and more precise. By using drugs like tamoxifen or aromatase inhibitors (AIs) such as letrozole, anastrozole, or exemestane, treatment can be personalized based on the hormonal profile of the cancer, which may improve outcomes and decrease the need for extensive surgery. This approach could lead to fewer side effects and a quicker recovery for patients.

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

Research has shown that treatments like tamoxifen and aromatase inhibitors (such as letrozole, anastrozole, and exemestane) effectively treat early-stage breast cancer that grows in response to estrogen (ER+ breast cancer). In this trial, all participants will receive pre-operative endocrine therapy, which may include tamoxifen or one of the aromatase inhibitors. Tamoxifen can lower the chance of breast cancer returning by 40% and reduce the risk of death by 30% after five years of use. Studies suggest that letrozole and anastrozole may work better than tamoxifen as the first treatment for early breast cancer. Aromatase inhibitors help by reducing estrogen levels, which can slow the growth of ER+ breast cancer. Overall, these treatments have a strong record of reducing the risk of cancer recurrence. ^{2 6 7 8 9}

Who Is on the Research Team?

Shayna L. Showalter

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10453164/

Extended Adjuvant Endocrine Therapy in Early Breast ... Taking tamoxifen for 5 years has been shown to reduce the risk of breast cancer recurrence by 40% and mortality by 30% compared to patients ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2104162

Duration of Adjuvant Aromatase-Inhibitor Therapy in ... Extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture.

3. ascopubs.org ascopubs.org/doi/10.1200/EDBK_350358

Personalizing Adjuvant Endocrine Therapy for Early-Stage ... The result was a 52% reduction in the combined endpoint of ductal carcinoma in situ or invasive cancer (either breast) for low-dose tamoxifen, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2001225/

A decade of letrozole: FACE - PMC Conclusions. Letrozole and anastrozole have both demonstrated superior efficacy compared with tamoxifen as initial therapy for early breast cancer [3, 4].

5. thelancet.com thelancet.com/article/s1470-2045(21)00758-0/fulltext

Aromatase inhibitors versus tamoxifen in premenopausal ... The absolute reduction in the 5-year risk of breast cancer recurrence was 3·2%, but no difference was apparent in breast cancer mortality. Few ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2690973/

Long-term efficacy and safety of anastrozole for adjuvant ... The results of the Oxford meta-analyses3,4 have demonstrated significant reduction in both disease recurrence (41%) and breast cancer specific mortality (34%) ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01013-X/fulltext

Extending the duration of endocrine treatment for early ... In postmenopausal women with oestrogen receptor-positive early breast cancer, 5 years of adjuvant tamoxifen substantially reduces 15-year ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0305737209001923

Adjuvant aromatase inhibitor therapy: Outcomes and safety The Anastrozole or Tamoxifen Alone or in Combination (ATAC) trial has compiled safety data for initial adjuvant AI therapy with anastrozole (ANA) versus TAM ...

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.69.2871

Comparative Efficacy and Safety of Adjuvant Letrozole ... On-treatment deaths occurring in the letrozole- versus anastrozole-treated patients were 42 (2.0%) versus 46 (2.2%; Table 2). The main causes of ...