Hormone Therapy + Chemotherapy for Breast Cancer

Recruiting at 1747 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Aromatase inhibitors, SERMs

Disqualifiers: Inflammatory breast cancer, Metastatic, 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: 3

Duration: 5-10 years

5018 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This randomized phase III clinical trial studies how well tamoxifen citrate, anastrozole, letrozole, or exemestane with or without chemotherapy work in treating patients with breast cancer that has spread from where it began in the breast to surrounding normal tissue (invasive). Estrogen can cause the growth of breast cancer cells. Hormone therapy, using tamoxifen citrate, may fight breast cancer by blocking the use of estrogen by the tumor cells. Aromatase inhibitors, such as anastrozole, letrozole, and exemestane, may fight breast cancer by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving tamoxifen citrate, anastrozole, letrozole, or exemestane is more effective with combination chemotherapy in treating patients with breast cancer.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, you must not have started chemotherapy or hormone therapy for breast cancer before joining the trial.

Is hormone therapy with anastrozole safe for breast cancer treatment?

Research shows that anastrozole, used in hormone therapy for breast cancer, generally has a favorable safety profile compared to tamoxifen. It is considered well-tolerated and potentially less toxic than some other treatments. ^{1 2 3 4 5}

What makes the drug combination of Anastrozole, Exemestane, Letrozole, and Tamoxifen Citrate unique for breast cancer treatment?

This drug combination is unique because it includes both aromatase inhibitors (Anastrozole, Exemestane, Letrozole) and Tamoxifen, which work together to block estrogen production and action, offering a comprehensive approach to treating hormone receptor-positive breast cancer in postmenopausal women. This combination is considered more effective and better tolerated than older treatments like megestrol acetate. ^{5 6 7 8 9}

What data supports the effectiveness of the drugs used in hormone therapy and chemotherapy for breast cancer?

Research shows that drugs like anastrozole and letrozole, which are aromatase inhibitors, are effective in treating breast cancer in postmenopausal women, especially when other treatments like tamoxifen have not worked. Letrozole, in particular, has been shown to improve disease-free survival and reduce the risk of cancer spreading, making it a recommended treatment for breast cancer. ^{4 5 10 11 12}

Who Is on the Research Team?

Kevin M Kalinsky

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for women aged 18+ who've had breast surgery and need radiation or mastectomy, with a performance status of 0-2. They must be able to receive certain chemotherapies, have node-positive invasive breast cancer that's estrogen/progesterone receptor positive and HER-2 negative. No recent other cancers (except some skin/cervical cancers) or chronic steroid/immunosuppressant use.

Inclusion Criteria

My breast cancer is hormone receptor positive, HER2 negative, and has spread to 1-3 lymph nodes.

I had surgery for breast cancer and will have or had radiation.

I can take care of myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

I am not on long-term steroids or drugs that weaken my immune system.

I have not started any chemotherapy or hormone therapy for my breast cancer.

I do not have inflammatory breast cancer or cancer that has spread.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a protocol-approved chemotherapy regimen and/or adjuvant endocrine therapy for 5-10 years

5-10 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 years

Every 3 months for 1 year, every 6 months for 4 years, then yearly for 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Exemestane
• Letrozole
• Systemic Chemotherapy
• Tamoxifen Citrate

Trial Overview The study compares the effectiveness of hormone therapies (tamoxifen citrate, anastrozole, letrozole, exemestane) alone versus combined with chemotherapy in treating invasive breast cancer. It aims to see which combination better stops tumor growth by blocking estrogen or killing/dividing cells.

How Is the Trial Designed?

Group I: Arm II (endocrine therapy) Experimental Treatment 6 Interventions

Patients receive a protocol-approved endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity.

Group II: Arm I (chemotherapy and endocrine therapy) Experimental Treatment 7 Interventions

Patients receive a protocol-approved chemotherapy regimen based on the patient and/or physician preference. Patients then receive a protocol-approved adjuvant endocrine therapy comprising tamoxifen citrate, an aromatase inhibitor (anastrozole, letrozole, or exemestane), or both for 5-10 years in the absence of disease progression or unacceptable toxicity.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Anastrozole is a potent and selective third-line aromatase inhibitor that offers a significant advancement in the treatment of hormone-sensitive breast cancer, particularly for postmenopausal women.

This review highlights anastrozole's biochemical properties and clinical efficacy, indicating its widespread use as a first- and second-line treatment option, potentially providing better outcomes and safety compared to traditional therapies like tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. Köberle, D., Thürlimann, B.[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 a study of 150 breast cancer patients, those receiving sequential treatment with letrozole and tamoxifen showed a higher overall response rate and fewer adverse reactions compared to those on letrozole alone.

Both treatment methods resulted in similar survival rates, but the sequential therapy group had a significantly lower recurrence rate and better improvement in blood lipid levels, indicating a potentially better prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma. Lu, X., Qian, C.[2023]

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, 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]

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]

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, 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]

Aromatase inhibitors like anastrozole, letrozole, and exemestane are now the preferred hormonal treatments for estrogen-receptor-positive, postmenopausal metastatic breast cancer, replacing older therapies such as tamoxifen.

Recent studies have confirmed the effectiveness of these aromatase inhibitors in managing breast cancer, highlighting their critical role in targeting the hormonal pathways involved in the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsteroidal and steroidal aromatase inhibitors in breast cancer. Hamilton, A., Volm, M.[2018]

Citations

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

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

2. England pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. [2018]

3. England pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

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

Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma. [2023]

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

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. [2022]

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

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. [2018]

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

Role of anastrozole in adjuvant therapy for postmenopausal patients. [2019]

8. England 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. [2022]

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

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

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

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

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

New developments in the treatment of postmenopausal breast cancer. [2018]

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

Nonsteroidal and steroidal aromatase inhibitors in breast cancer. [2018]