Hormone Therapy for Breast Cancer

(POWER II Trial)

Recruiting at 2 trial locations

Overseen By Meagan Miller

Age: 65+

Sex: Female

Trial Phase: Phase 3

Sponsor: University of Virginia

Must be taking: Endocrine therapy

Must not be taking: Strong CYP2D6 inhibitors

Disqualifiers: Bilateral breast cancer, Multicentric disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

354 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores hormone therapy options for women with early-stage breast cancer before surgery. Researchers will randomly assign participants to one of two groups: one receiving hormone pills (endocrine therapy) for three months before surgery, and the other proceeding directly to surgery. The trial aims to assess how well patients tolerate the hormone treatment and its impact on their overall care experience. Women aged 65 and older with a specific type of breast cancer (ER+) and no significant node involvement may be suitable candidates, particularly if they plan to undergo surgery and can take oral medication. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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 participate if you are currently using or plan to use strong CYP2D6 inhibitors like Fluvoxamine or Paroxetine.

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

Research has shown that the treatments tested in this trial—Anastrozole, Exemestane, Letrozole, and Tamoxifen—are generally safe and well-tolerated for breast cancer patients.

Anastrozole significantly lowers the risk of breast cancer recurrence and reduces deaths specifically from breast cancer. It has been used for a long time with positive results.

Exemestane also has a strong safety record. It often works better and is safer than Tamoxifen. Some studies have shown it can reduce the risk of developing invasive breast cancer by 65%.

Letrozole has been studied for safety as well. It has demonstrated high survival rates for patients using it over several years, similar to Anastrozole.

Tamoxifen is well-known for cutting the risk of breast cancer by half in some cases. It also reduces the chance of dying from breast cancer by 57%.

These treatments are already approved for other uses and mostly have mild side effects, making them a trusted choice in fighting breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the hormone therapies Anastrozole, Exemestane, Letrozole, and Tamoxifen because they offer a tailored approach to treating breast cancer. Unlike chemotherapy, which targets all rapidly dividing cells, these treatments specifically target hormone receptors involved in the growth of certain breast cancer cells. Anastrozole, Exemestane, and Letrozole are aromatase inhibitors that reduce estrogen levels, while Tamoxifen blocks estrogen receptors on cancer cells. This targeted action not only aims to be more effective but also tends to result in fewer side effects compared to traditional chemotherapy.

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

Research has shown that hormone therapy effectively treats early-stage estrogen receptor-positive (ER+) breast cancer. In this trial, participants in the intervention arm will receive 90 days of pre-endocrine therapy (ET) with either Tamoxifen or an aromatase inhibitor (Anastrozole, Exemestane, or Letrozole) before breast cancer surgery. Anastrozole significantly lowered the chance of cancer recurrence by 41% and reduced breast cancer deaths by 34%. Exemestane showed a 65% reduction in the yearly occurrence of invasive breast cancer in postmenopausal women at higher risk. Letrozole effectively increased the time patients remain cancer-free, with a notable decrease in new tumor development. Tamoxifen demonstrated a 38% reduction in breast cancer cases and a 57% decrease in breast cancer deaths. These treatments generally lower the risk of breast cancer returning and improve survival rates in patients with ER+ breast cancer. ^{1 2 4 6 7}

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 estrogen receptor positive (ER+) breast cancer. Participants will either receive pre-operative endocrine therapy or follow standard care before surgery.

Inclusion Criteria

Provision of signed and dated informed consent form

I am eligible for and have chosen breast-conserving surgery.

I am eligible for hormone therapy for my cancer.

Exclusion Criteria

I have cancer in both breasts at the same time.

I have another cancer that is growing or needs treatment.

I have had radiation therapy on the same side 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 90 days of pre-operative endocrine therapy to assess tolerance and inform radiation therapy decisions

12 weeks

Regular visits for patient-reported outcome assessments

Breast Cancer Surgery

Participants undergo breast cancer surgery, either directly or after pre-operative endocrine therapy

1 week

1 visit (in-person)

Adjuvant Therapy

Participants may receive adjuvant radiation therapy and are recommended for adjuvant endocrine therapy if appropriate

24 months

Follow-up visits for monitoring adherence and outcomes

Follow-up

Participants are monitored for safety, effectiveness, and recurrence over a long-term period

5 years

Annual visits for outcome assessments

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Exemestane
• Letrozole
• Tamoxifen

Trial Overview

The study compares the effects of taking Tamoxifen, Letrozole, Anastrozole, or Exemestane for three months before surgery versus proceeding directly to surgery without these drugs in women with ER+ breast cancer.

How Is the Trial Designed?

Group I: Intervention Arm Experimental Treatment 1 Intervention

90 days of pre-ET (endocrine therapy - tamoxifen or aromatase inhibitor) before Breast Cancer Surgery

Group II: Control Arm Active Control 1 Intervention

Will proceed directly to Breast Cancer Surgery

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

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?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

Anastrozole and letrozole significantly improve disease-free survival compared to tamoxifen in postmenopausal women with early-stage breast cancer, based on results from Phase III trials.

Switching to an aromatase inhibitor like anastrozole or exemestane after 2 to 3 years of tamoxifen therapy reduces the risk of cancer recurrence more effectively than continuing tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer. Berry, J.[2007]

Letrozole, an aromatase inhibitor, has been shown to significantly improve disease-free survival in breast cancer patients, particularly those at higher risk of relapse, compared to tamoxifen, making it a recommended initial adjuvant therapy.

In addition to its initial use, letrozole also provides benefits when given after 5 years of tamoxifen treatment, with its efficacy increasing with longer treatment durations, highlighting its potential in future combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a well-tolerated and effective treatment for breast cancer. Bundred, NJ.[2016]

A systematic review of 10 trials found that third-generation aromatase inhibitors (anastrozole, letrozole, and exemestane) significantly improve disease-free survival in post-menopausal women with early-stage, hormone receptor-positive breast cancer compared to tamoxifen.

The meta-analysis indicated that aromatase inhibitors also enhance overall survival, particularly in node-positive patients, suggesting they are a strong alternative to tamoxifen for adjuvant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in adjuvant therapy for hormone receptor positive breast cancer: a systematic review. Eisen, A., Trudeau, M., Shelley, W., et al.[2018]

The ATAC trial, involving over 9,000 postmenopausal women, demonstrated that anastrozole significantly improves disease-free survival and reduces recurrence rates compared to tamoxifen, with benefits continuing even after treatment ends.

Anastrozole also has a favorable safety profile compared to tamoxifen, suggesting it may be a better initial treatment option for early breast cancer, especially when considering long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. Buzdar, AU., Cuzick, J.[2018]

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]

Anastrozole and letrozole are effective oral treatments for advanced breast cancer in postmenopausal women, especially when other therapies like tamoxifen have not worked.

Both drugs are claimed to be more effective and less toxic than the standard treatment, megestrol acetate, although the review assesses the validity of these claims.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

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]

In a study of 40 postmenopausal women with locally advanced breast cancer, both Letrozole and Tamoxifen were found to be effective as neoadjuvant hormone therapies, with 25% of patients on Tamoxifen and 20% on Letrozole not achieving a complete response, leading to subsequent radiotherapy.

The study indicated that neoadjuvant hormone therapy was generally well-tolerated, with side effects occurring in 55% of patients on Letrozole and 60% on Tamoxifen, suggesting that these treatments could improve clinical outcomes and allow for successful radical mastectomy in patients with better prognoses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Letrozole vs. tamoxifen as neoadjuvant therapy for postmenopausal patients with hormone-dependent locally-advanced breast cancer]. Novoa Vargas, A., Font López, KC., Amador, DD.[2018]

In a study involving 6182 postmenopausal women with hormone-receptor-positive breast cancer, sequential treatment with tamoxifen and letrozole did not significantly improve disease-free survival compared to letrozole monotherapy, indicating that letrozole alone may be sufficient for treatment.

The updated analysis showed no statistically significant difference in overall survival between letrozole and tamoxifen monotherapy, suggesting that both treatments have similar long-term outcomes, with adverse events consistent with previous reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., et al.[2022]

The ATAC trial is one of the few studies that directly compares aromatase inhibitors (AIs) for breast cancer treatment, providing valuable insights into their effectiveness.

Emerging evidence suggests a proposed sequence of hormonal therapies, including anastrozole and tamoxifen, tailored for different patient populations, which could optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy in early and advanced breast cancer. Buzdar, AU.[2019]

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]

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]

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Taking Arimidex for 10 years after breast cancer surgery reduced recurrence risk, but didn't improve overall survival.

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