Hormone Therapy for Early Stage Breast Cancer

Overseen By Yvonne E Taul, RN

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Veronica Morgan Jones

Must be taking: Anti-endocrine

Must not be taking: Investigational agents

Disqualifiers: Progesterone negativity, High grade tumor, 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

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests hormone therapy options for treating early-stage breast cancer rich in estrogen. Researchers aim to determine if using this treatment before surgery aids in more complete cancer removal. Participants will begin with Anastrozole, a hormone therapy drug, and may switch medications if they experience intolerance. The trial seeks postmenopausal women with early-stage, estrogen-rich breast cancer without significant lymph node involvement. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on investigational agents that could affect the trial, you may need to stop those.

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

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

Studies have found that Anastrozole often causes fewer serious side effects than Tamoxifen for postmenopausal women with early-stage breast cancer. Letrozole effectively lowers the chance of cancer returning and is commonly used for postmenopausal women with hormone-sensitive breast cancer.

Exemestane is considered safe after Tamoxifen treatment and has successfully reduced the risk of cancer recurrence. While Tamoxifen is effective, it can increase the risk of blood clots and uterine cancer, but it has been well-studied and used for many years.

These medications have FDA approval for treating breast cancer, establishing their safety records. However, individual reactions can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these hormone therapies for early-stage breast cancer because they offer a personalized approach to treatment. Unlike standard treatments that might be one-size-fits-all, this protocol allows patients to switch between Anastrozole, Letrozole, Exemestane, and Tamoxifen based on their individual tolerance and response. This flexibility not only aims to improve patient comfort but also seeks to enhance treatment efficacy by tailoring the therapy to each patient's needs.

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

Research has shown that Anastrozole, initially given to participants in this trial, can reduce the risk of breast cancer recurrence by 41% and decrease breast cancer deaths by 34%. If participants cannot tolerate Anastrozole, they will switch to Letrozole, which also lowers the risk of breast cancer and extends the time patients remain disease-free. If Letrozole is not tolerated, participants will then switch to Exemestane, which, compared to Tamoxifen, reduces the risk of breast cancer recurrence or death by 24%. Finally, if Exemestane is not tolerated, participants will switch to Tamoxifen, which has been found to reduce the risk of dying from breast cancer by about one-third over 15 years. Each treatment in this trial has proven effective in lowering the chance of breast cancer returning and in helping patients live longer. ^{3 6 7 8 9}

Who Is on the Research Team?

Irada Ibrahim-zada, MD

Principal Investigator

University of Kentucky

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with early stage I-II, estrogen-rich breast cancer that's not spread to lymph nodes. They must be able to take anti-endocrine therapy and sign a consent form. Women with progesterone-negative tumors, high-grade tumors, other cancers, or allergies to the study drugs can't join.

Inclusion Criteria

My breast cancer is confirmed and is in the early stages (I or II).

Ability to understand and the willingness to sign a written informed consent document

My doctor says I can receive hormone therapy for my cancer.

Exclusion Criteria

Receiving any other investigational agents that could impact the efficacy of this trial regimen

I am allergic to certain cancer medications like Anastrozole or Tamoxifen.

I do not have any unmanaged ongoing illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Endocrine Therapy

Participants receive neoadjuvant endocrine therapy with Anastrozole, Letrozole, Exemestane, or Tamoxifen for 6 months

6 months

Surgery

Participants undergo breast conservation surgery to evaluate margin status

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of residual cancer burden and satisfaction with cosmetic outcome

6-12 months

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole 1mg
• Exemestane 25 mg
• Letrozole 2.5mg
• Tamoxifen

Trial Overview The study tests if using neoadjuvant endocrine therapy (Anastrozole, Letrozole, Exemestane or Tamoxifen) before surgery improves outcomes in breast cancer by increasing the chances of completely removing the tumor without leaving any cancerous tissue at the edges.

How Is the Trial Designed?

Group I: Neoadjuvant Endocrine Therapy Experimental Treatment 4 Interventions

Participants will begin treatment with Anastrozole. If not tolerated well, participants will discontinue and begin treatment using Letrozole. If not tolerated well, participants will discontinue and begin treatment using Exemestane. If not tolerated well, participants will discontinue and begin treatment on Tamoxifen.

Anastrozole 1mg is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Hormone receptor-positive breast cancer

Approved in United States as Arimidex for:

• Hormone receptor-positive breast cancer
• Prevention of breast cancer in high-risk individuals

Approved in Canada as Arimidex for:

• Hormone receptor-positive breast cancer

Approved in Japan as Arimidex for:

• Hormone receptor-positive breast cancer

Who Is Running the Clinical Trial?

Veronica Morgan Jones

Lead Sponsor

Trials

1

Recruited

70+

Irada Ibrahim-zada

Lead Sponsor

Erin Burke

Lead Sponsor

Trials

1

Recruited

70+

Emily Marcinkowski

Lead Sponsor

Trials

1

Recruited

70+

Published Research Related to This Trial

Adjuvant hormonal therapy with tamoxifen significantly reduces the risk of breast cancer recurrence and death in women with early-stage, hormone receptor-positive breast cancer, but it also carries risks of endometrial cancer and thromboembolic events.

Recent trials, including the MA-17 and Intergroup Exemestane Study, show that selective aromatase inhibitors (AIs) like anastrozole and exemestane provide superior disease-free survival compared to tamoxifen, establishing AIs as a preferred treatment option for postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? Chung, CT., Carlson, RW.[2019]

Third-generation aromatase inhibitors (AIs) like anastrozole, exemestane, and letrozole have shown superior efficacy compared to tamoxifen in treating hormone-receptor-positive breast cancer in postmenopausal women, particularly in neoadjuvant and adjuvant settings.

Letrozole, when used as extended adjuvant therapy after 5 years of tamoxifen, significantly improved disease-free survival and overall survival in node-positive patients, highlighting its effectiveness in long-term treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The breast cancer continuum in hormone-receptor-positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors. Rugo, HS.[2022]

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]

In a study of 686 postmenopausal women with early breast cancer, both anastrozole and exemestane showed comparable treatment-related symptoms (TRS) and health-related quality of life (HRQL) over 5 years, indicating similar tolerability between the two aromatase inhibitors.

However, a significant burden of TRS was linked to poorer HRQL, and women who experienced more side effects before starting treatment were more likely to discontinue therapy early, highlighting the importance of managing side effects to improve treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported predictors of early treatment discontinuation: treatment-related symptoms and health-related quality of life among postmenopausal women with primary breast cancer randomized to anastrozole or exemestane on NCIC Clinical Trials Group (CCTG) MA.27 (E1Z03). Wagner, LI., Zhao, F., Goss, PE., et al.[2023]

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]

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]

In postmenopausal women with hormone receptor positive early-stage breast cancer, letrozole is more cost-effective than anastrozole for both treatment-naïve patients and those already on letrozole, with a cost per quality-adjusted life-year (QALY) gained ranging from $20,276 to $34,356.

Starting treatment with letrozole results in a gain of 0.15 QALYs compared to anastrozole, despite letrozole being $3916 more expensive over a lifetime, indicating its superior efficacy in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer. Lipsitz, M., Delea, TE., Guo, A.[2019]

Letrozole is an effective treatment for postmenopausal women with early-stage or advanced hormone-sensitive breast cancer, showing a 43% reduction in disease recurrences when used as extended adjuvant therapy beyond standard tamoxifen treatment.

In advanced breast cancer, letrozole outperformed tamoxifen in terms of time to disease progression (9.4 months vs. 6.0 months) and has a similar tolerability profile, making it a recommended first-line therapy according to treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in postmenopausal women with breast cancer. Simpson, D., Curran, MP., Perry, CM.[2018]

Letrozole, an aromatase inhibitor, has been shown to be significantly more effective than tamoxifen in treating advanced breast cancer, particularly in terms of median time to progression and response rates, while being well tolerated by patients.

Anastrozole and exemestane also provide effective alternatives to tamoxifen, with anastrozole showing equivalent efficacy overall but superior results in hormone receptor-positive patients, and exemestane demonstrating better response rates, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in advanced breast cancer. Mouridsen, HT.[2019]

In patients with Stage IV hormone-sensitive breast cancer, DHEA-S levels of 89 microg/dL or higher were associated with disease progression, indicating that monitoring DHEA-S could be crucial for predicting treatment outcomes.

In vitro studies showed that elevated DHEA-S levels promoted the proliferation of certain breast cancer cells, suggesting that DHEA-S may act as an estrogenic agent, which could contribute to cancer progression in low estrogen environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dehydroepiandrosterone-sulfate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a renewed role for adrenalectomy. Morris, KT., Toth-Fejel, S., Schmidt, J., et al.[2013]

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]

Anastrozole, a highly specific aromatase inhibitor, has emerged as a potentially better tolerated and more effective treatment for postmenopausal patients with hormone-sensitive breast cancer compared to tamoxifen, which has safety and tolerability issues.

The ongoing Arimidex, Tamoxifen, Alone or in Combination trial indicates that anastrozole is an effective and well-tolerated option for adjuvant endocrine treatment in early breast cancer, suggesting its potential role in chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anastrozole in adjuvant therapy for postmenopausal patients. 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]

Anastrozole is as effective as tamoxifen for treating advanced breast cancer in postmenopausal women, showing a slightly higher objective response rate (21% vs. 17%) and a significant clinical benefit in 59% of patients compared to 46% for tamoxifen.

Anastrozole offers a significant advantage in time to progression (median of 11.1 months vs. 5.6 months for tamoxifen) and has a lower incidence of side effects, such as thromboembolic events and vaginal bleeding, making it a preferable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Nabholtz, JM., Buzdar, A., Pollak, M., et al.[2022]

Citations

1. 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%) ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(19)32955-1/fulltext

Use of anastrozole for breast cancer prevention (IBIS-II) Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase ...

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

Duration of Adjuvant Aromatase-Inhibitor Therapy in ... Despite substantial improvements in outcome resulting from the use of adjuvant endocrine therapy among women with luminal breast cancer, the ...

4. breastcancer.org breastcancer.org/research-news/10-years-arimidex

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

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1526820911703500

Anastrozole as Adjuvant Therapy for Early-Stage Breast ... Anastrozole was the first drug to show improved efficacy and safety compared with standard therapies for first- and second-line therapy of hormone-sensitive ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2011/020541s026lbl.pdf

Arimidex (anastrozole) tablet label - accessdata.fda.gov ARIMIDEX is indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/anastrozole-oral-route/description/drg-20061868

Anastrozole (oral route) - Side effects & dosage Anastrozole is used to treat early hormone receptor-positive breast cancer. It is also used for first-line treatment of hormone receptor-positive or hormone ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204506707677

Articles Comprehensive side-effect profile of anastrozole ... Anastrozole is tolerated better than tamoxifen by postmenopausal women with early-stage breast cancer, and results in fewer serious adverse events.

9. medicalnewstoday.com medicalnewstoday.com/articles/arimidex

Arimidex: Side effects, dosage, uses, and more For early breast cancer that is HR-positive, Arimidex is given to lower the risk of the breast cancer coming back or spreading after it's already been treated ...