Hormone Therapy + Chemotherapy for Breast Cancer

Not currently recruiting at 1811 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the effectiveness of hormone therapy with or without chemotherapy for breast cancer that has spread beyond the breast. Researchers seek to evaluate whether drugs like tamoxifen citrate or aromatase inhibitors (which lower estrogen levels, such as anastrozole, exemestane, and letrozole) are more effective alone or when combined with chemotherapy. Women with breast cancer that has spread to nearby tissue, who have not yet started treatment, may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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

Research has shown that the treatments under study—anastrozole, exemestane, letrozole, and tamoxifen citrate—are generally well-tolerated. Anastrozole has proven safe over the long term, reducing the chances of breast cancer recurrence and lowering the risk of death from breast cancer. Exemestane is considered safer than tamoxifen and helps reduce the risk of developing invasive breast cancer. Letrozole has a strong safety record and significantly decreases the number of new breast cancer cases. Tamoxifen, used for a long time, is known to reduce both the risk of dying from breast cancer and its recurrence.

Although each treatment has its own side effects, many patients have used these medications safely. This study is in a late phase, indicating that earlier research has thoroughly checked safety. Consulting a healthcare provider is essential to understand what this means for participation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these hormone therapies combined with chemotherapy because they offer a potentially more personalized approach to treating breast cancer. Unlike traditional treatments that might focus solely on chemotherapy or hormone therapy, this combination allows for tailored regimens based on individual patient and physician preference. This approach aims to improve outcomes by using a mix of chemotherapy and endocrine therapies like anastrozole, letrozole, exemestane, or tamoxifen citrate, which are known to target hormone receptors in cancer cells. By combining these treatments, there's hope for not only halting disease progression but also minimizing side effects and toxicity, which can be a significant concern with conventional treatments.

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

Research has shown that tamoxifen citrate, anastrozole, letrozole, and exemestane effectively treat breast cancer. In this trial, participants in Arm I will receive chemotherapy followed by one of these endocrine therapies, while participants in Arm II will receive endocrine therapy alone. Tamoxifen can lower the risk of dying from breast cancer by about 33% over 15 years. Anastrozole significantly reduces the chances of cancer recurrence by 41% and lowers the risk of dying from breast cancer by 34%. Letrozole also helps prevent cancer from returning, improving the time women remain free of the disease. Exemestane has reduced the risk of breast cancer recurrence or death by 24% compared to tamoxifen. These treatments work by blocking or reducing estrogen, which can help some breast cancer cells grow. ^{1 2 3 6 7}

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 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 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]

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]

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]

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]

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]

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]

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 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]

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. 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.

4. news.cancerresearchuk.org news.cancerresearchuk.org/2023/11/07/anastrozole-licensed-prevent-breast-cancer-high-risk-women/

Thousands of women offered anastrozole to help prevent ... Cases of invasive oestrogen receptor-positive breast cancer specifically were reduced by 54%, and ductal carcinoma in situ by 59%, especially in ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37079878/

Postoperative Adjuvant Anastrozole for 10 or 5 Years in ... Although no difference in overall survival was observed as in other trials, extended anastrozole therapy could be one treatment choice in ...

6. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044750

Aromatase Inhibitors and the Risk of Cardiovascular ... These drugs have been associated with favorable clinical outcomes, including decreased risks of all-cause and breast cancer–related mortality, ...

7. breastcancer.org breastcancer.org/research-news/risk-reducing-effects-of-arimidex-last-years

Risk-Reducing Effects of Arimidex for High- ... The new results show that women who took Arimidex were 50% less likely to be diagnosed with breast cancer than women who didn't take Arimidex.