Hormone Therapy for Early Stage Breast Cancer
Recruiting in Palo Alto (17 mi)
Overseen byVeronica M Jones, MD
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
The goal of this study is to access whether treatment of early state estrogen-rich breast cancers with neoadjuvant endocrine therapy will result in higher rates of margin negativity on lumpectomy specimen.
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.
What data supports the effectiveness of the drugs Anastrozole, Letrozole, Exemestane, and Tamoxifen for early-stage breast cancer?
Research shows that Anastrozole, Letrozole, and Exemestane, which are aromatase inhibitors, are more effective than Tamoxifen in improving disease-free survival in postmenopausal women with hormone receptor-positive early-stage breast cancer. Studies like the ATAC trial and others have demonstrated that these drugs are superior to Tamoxifen, making them a preferred choice for adjuvant hormonal therapy.12345
Is hormone therapy for early-stage breast cancer safe for humans?
The ATAC trial, which studied anastrozole and tamoxifen in over 9,000 postmenopausal women with early-stage breast cancer, found that anastrozole has a favorable safety profile compared to tamoxifen. Anastrozole and other aromatase inhibitors like letrozole and exemestane are generally well-tolerated, though long-term safety profiles may differ among them.678910
How does this drug differ from other treatments for early-stage breast cancer?
This drug regimen includes aromatase inhibitors (anastrozole, exemestane, letrozole) and tamoxifen, which are used to block estrogen production or its effects, offering an alternative to traditional hormone therapies. Aromatase inhibitors are particularly effective in postmenopausal women and have been shown to be more effective and better tolerated than some older treatments like megestrol acetate.1011121314
Eligibility Criteria
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.
See 2 more
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.
See 4 more
Trial Timeline
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
Treatment Details
Interventions
- Anastrozole 1mg (Aromatase Inhibitor)
- Exemestane 25 mg (Aromatase Inhibitor)
- Letrozole 2.5mg (Aromatase Inhibitor)
- Tamoxifen (Selective Estrogen Receptor Modulator)
Trial OverviewThe 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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Neoadjuvant Endocrine TherapyExperimental Treatment4 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, Australia 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
🇦🇺 Approved in Australia as Arimidex for:
- Hormone receptor-positive breast cancer
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Kentucky Markey Cancer CenterLexington, KY
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Who Is Running the Clinical Trial?
Veronica Morgan JonesLead Sponsor
Erin BurkeLead Sponsor
Emily MarcinkowskiLead Sponsor
References
Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer. [2019]The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in July 2010 and letrozole in June 2011, there may be financial pressures prior to letrozole's generic availability to start treatment-naïve patients on anastrozole vs. letrozole or to switch patients already receiving letrozole to anastrozole.
New developments in the treatment of postmenopausal breast cancer. [2018]In recent years, new agents have challenged tamoxifen as the standard endocrine therapy for postmenopausal breast cancer. This article reviews developments with regard to the third-generation aromatase inhibitors (AIs)--anastrozole, letrozole and exemestane--and fulvestrant, the first of a new type of estrogen receptor antagonist that, unlike tamoxifen, has no partial agonist activity. The final results of the "Arimidex", Tamoxifen, Alone or in Combination (ATAC) trial, at a median follow-up of more than five years, and recent results from switching studies with anastrozole and exemestane, strengthen the position of these AIs as adjuvant treatment for hormone receptor-positive early breast cancer. Sequencing options for the future are also discussed because non-steroidal AIs are increasingly used early in the treatment sequence.
Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? [2019]Adjuvant hormonal therapy in the treatment of women with early-stage, hormone receptor (HR)-positive breast cancer is now considered the standard of care. Adjuvant tamoxifen decreases the risk of breast cancer recurrence and death in women with early-stage breast cancer when taken for 5 years. The benefits of tamoxifen are counterbalanced by toxicities including an increased risk of endometrial cancer and thromboembolic events. The selective aromatase inhibitors (AIs)--including anastrozole, letrozole, and exemestane--are challenging the role of tamoxifen as the adjuvant hormonal therapy of choice in postmenopausal women. Results of the Arimidex and Tamoxifen Alone or in Combination trial favor the use of anastrozole over tamoxifen as initial adjuvant hormonal therapy, with improvement in disease-free survival (DFS) and a favorable toxicity profile. The results of 2 large adjuvant trials using AIs sequentially with tamoxifen in postmenopausal women with early-stage, HR-positive breast cancer have been reported. The MA-17 study randomized women to placebo or letrozole for 5 years after completion of 4.5-6 years of initial tamoxifen. The Intergroup Exemestane Study (IES) randomized women following 2-3 years of adjuvant tamoxifen to continue to receive tamoxifen or switch to exemestane for a total of 5 years of adjuvant hormonal therapy. The MA-17 and IES trials demonstrated superior DFS with the AI and corroborated the smaller GROCTA-4B and Italian Tamoxifen Arimidex trials, which studied sequential therapy with aminoglutethamide or anastrozole. There is now substantial medical evidence supporting the use of AIs in postmenopausal women with early-stage, HR-positive breast cancer.
Letrozole: a review of its use in postmenopausal women with breast cancer. [2018]Letrozole (Femara), a nonsteroidal, third-generation aromatase inhibitor administered orally once daily, has shown efficacy in the treatment of postmenopausal women with early-stage or advanced, hormone-sensitive breast cancer. In early-stage disease, extending adjuvant endocrine therapy with letrozole (beyond the standard 5-year period of tamoxifen) improved disease-free survival; compared with placebo there was a 43% relative reduction in disease recurrences or new contralateral breast tumours at a median follow-up of 2.4 years. The results of 4 months' neoadjuvant treatment with letrozole or tamoxifen in postmenopausal women with untreated primary disease favour letrozole. In advanced breast cancer, letrozole was superior to tamoxifen as first-line treatment; time to disease progression was significantly longer (9.4 vs 6.0 months, p
The breast cancer continuum in hormone-receptor-positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors. [2022]There are now a number of highly effective options for the treatment of hormone-receptor-positive breast cancer. Although tamoxifen was the standard hormonal treatment for many years, we now have another option for postmenopausal women: the third-generation aromatase inhibitors (AIs) anastrozole, exemestane and letrozole. A number of trials have investigated the use of third-generation AIs compared with tamoxifen throughout the continuum of treatment settings for postmenopausal women with breast cancer. In the neoadjuvant setting, letrozole, given for 4 months, resulted in better overall clinical response and breast-conserving surgery rates than tamoxifen. The Immediate Preoperative Anastrozole Tamoxifen or Combined with Tamoxifen trial gave anastrozole for 3 months with no difference in clinical response but significantly improved breast-conserving surgery rates. Compared with tamoxifen, anastrozole and letrozole significantly improved disease-free survival as early adjuvant treatment for hormone-receptor-positive disease. Switching to anastrozole or exemestane after 2 to 3 years of adjuvant tamoxifen for a total of 5 years of therapy was also more effective than continued tamoxifen. All three agents are approved in the early adjuvant or switching setting in the USA. Letrozole following 5 years of tamoxifen as extended adjuvant treatment improved disease-free survival and, in the node-positive subgroup, overall survival when compared with placebo. Anastrozole and letrozole are both approved for the first-line treatment of hormone-sensitive advanced breast cancer in postmenopausal women; letrozole showed an improved response rate compared with tamoxifen. Anastrozole, letrozole and exemestane are all indicated for the second-line treatment of advanced breast cancer. In summary, third-generation AIs have been shown to have superior efficacy over tamoxifen in the metastatic, neoadjuvant and adjuvant settings and to improve outcome as extended adjuvant therapy following 5 years of tamoxifen. Ongoing studies will further define the role of sequential adjuvant treatment. Appropriate duration of treatment is another important area of investigation. This review will cover hormonal therapy for postmenopausal women with breast cancer and will not address the treatment of premenopausal women.
Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. [2018]The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial compared the efficacy and safety of anastrozole versus tamoxifen versus the combination as initial adjuvant treatment for early breast cancer in over 9,000 postmenopausal women. Analyses at 33 and 47 months median follow-up showed that anastrozole significantly prolonged disease-free survival and time to recurrence and reduced the incidence of contralateral breast cancer compared with tamoxifen. Results of the completed treatment analysis at 68 months median follow-up confirmed the earlier findings, showing that the absolute difference in disease-free survival continued to increase beyond completion of treatment. Mature safety data from the ATAC trial show that, overall, anastrozole has a favorable safety profile compared with tamoxifen. In the absence of current data on further follow-up or the outcome of trials investigating proactive sequencing of endocrine therapies, we present a model based on several trials, including ATAC. This model suggests that using an aromatase inhibitor as initial adjuvant therapy is a better option than switching to an aromatase inhibitor after >/=2 years of tamoxifen. The relative toxicities of the three approved third-generation aromatase inhibitors, anastrozole, letrozole, and exemestane, are discussed. These data suggest that long-term safety profiles may differ between aromatase inhibitors, although comprehensive comparative data for letrozole and exemestane versus tamoxifen are lacking.
Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. [2022]The Arimidex (anastrozole), Tamoxifen, Alone or in Combination (ATAC) trial was designed to compare the efficacy and safety of anastrozole with tamoxifen as adjuvant treatment for postmenopausal women with early-stage breast cancer. After an extended follow-up beyond the 5 years of treatment, we aimed to assess the safety, tolerability, and risk-benefit indices of these compounds.
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. [2022]The efficacy and tolerability of anastrozole (Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) and tamoxifen were compared as first-line therapy for advanced breast cancer in 353 postmenopausal women.
Role of anastrozole in adjuvant therapy for postmenopausal patients. [2019]For the past 25 years tamoxifen has been the mainstay for adjuvant treatment of postmenopausal patients with hormone-sensitive breast cancer. However, tamoxifen has some safety and tolerability issues, and its partial estrogen-receptor agonist activity may have efficacy implications. Highly specific aromatase inhibitors, of which anastrozole was the first, were introduced in the 1990s and have emerged as a potentially better tolerated and more effective class of agents targeting hormonally responsive breast cancer. This article provides a review of the clinical pharmacology of anastrozole (1 mg once daily) and reviews the first results of the ongoing Arimidex, Tamoxifen, Alone or in Combination early breast cancer trial, initiated in 1996. This randomized, double-blind multicenter trial compared tamoxifen (20 mg once daily) with anastrozole (1 mg once daily) alone and the combination of anastrozole plus tamoxifen, as adjuvant endocrine treatment for postmenopausal patients with operable, invasive, early breast cancer. The results of the Arimidex, Tamoxifen, Alone or in Combination trial show anastrozole to be an effective and well tolerated endocrine option for early breast cancer and provide evidence for its potential role in chemoprevention.
New aromatase inhibitors for breast cancer. [2019]Anastrozole (Arimidex-Zeneca) and letrozole (Femara-Novartis) are the first selective, oral, non-steroidal aromatase inhibitors. They are licensed for the treatment of advanced breast cancer in postmenopausal women where tamoxifen or other anti-oestrogen therapy has failed. The manufacturers of both drugs claim that their products are more effective, less toxic and better tolerated than the progestogen megestrol acetate, the standard therapy in this clinical situation. We assess these claims.
Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer. [2007]Five years of tamoxifen therapy has been the standard of care for the adjuvant treatment of estrogen receptor-positive early-stage breast cancer for many years and was the first hormonal treatment for postmenopausal women with advanced or metastatic disease. The third-generation aromatase inhibitors (AIs) anastrozole, exemestane, and letrozole offer new treatment options, although their efficacy has not been compared directly in randomized, double-blind, controlled trials in any breast cancer treatment setting.
Aromatase inhibitors in advanced breast cancer. [2019]The third-generation aromatase inhibitors suppress whole-body estrogen production in postmenopausal women with high specificity and potency. In women with hormone-sensitive breast cancer, three of these agents, letrozole, anastrozole, and exemestane, provide an important alternative endocrine therapy to the antiestrogen tamoxifen, which blocks estrogen activation of the estrogen receptor. For treatment of advanced or metastatic breast cancer that has progressed on first-line tamoxifen, all three agents are active. On that basis, they have each been compared with tamoxifen as first-line therapy of advanced breast cancer, in phase III trials. Letrozole was significantly superior to tamoxifen in the primary end point, median time to progression, as well as in response rate and clinical benefit rate, and treatment was well tolerated. Although there was no significant difference in median overall survival, an advantage seen with letrozole for the first 2 years may have been lost because of crossover to the alternate agent at disease progression. Anastrozole was evaluated in two separate trials designed for combined analysis. Overall, anastrozole was at least equivalent to tamoxifen in activity, but clearly superior only for median time to progression in the subgroup of patients with hormone receptor-positive disease. Treatment was generally as well tolerated as tamoxifen. In an early report, exemestane was significantly better than tamoxifen in response rate and median time to progression, with overall survival data not yet available. To date, letrozole appears to be the most effective aromatase inhibitor in the first-line advanced breast cancer setting.
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). [2023]Aromatase inhibitors are the most commonly prescribed adjuvant endocrine therapy for hormone-dependent early breast cancer in postmenopausal women. Among Canadian Cancer Trials Group MA.27 participants, anastrozole and exemestane had comparable 5-year event-free survival. This companion study examined differences in patient-reported treatment-related symptoms (TRS) and health-related quality of life (HRQL) among postmenopausal women randomized to anastrozole or exemestane.
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. [2013]Stage IV hormone-sensitive breast cancer is often treated with aromatase inhibitors (anastrozole, letrozole, exemestane), which block the conversion of dehydroepiandrosterone (DHEA) to estrone and estradiol. This is intended to obviate the need for steroid replacement and antiquate adrenalectomy.