Aromatase Inhibitors for Breast Cancer in Overweight and Obese Women

Overseen By Emily C Bellavance, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of Maryland, Baltimore

Must be taking: Aromatase inhibitors

Disqualifiers: Other malignancy, Investigational agents, Allergies, 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)

Compensation: Varies

Number of Visits: Unknown

Duration: 2-4 weeks

42 Participants Needed

Trial Summary

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 must not have received any prior chemotherapy, radiation therapy, or endocrine therapy for your current breast cancer. If you were taking tamoxifen or raloxifene for prevention, you need to have stopped at least one month before joining the study.

What data supports the effectiveness of the drug Anastrozole, Arimidex, Letrozole, Femara, Letrozole for breast cancer in overweight and obese women?

Research shows that letrozole, one of the drugs in this treatment, is more effective than anastrozole in treating advanced breast cancer, especially in patients with hormone receptor-positive tumors. Additionally, aromatase inhibitors like letrozole are effective in reducing estrogen levels, which is important for treating breast cancer in postmenopausal women. ^{1 2 3 4 5}

Is it safe for overweight and obese women to use aromatase inhibitors like Anastrozole and Letrozole for breast cancer?

Anastrozole (Arimidex) and Letrozole (Femara) are generally considered safe for treating breast cancer in postmenopausal women, with most side effects being mild, such as hot flashes, joint pain, nausea, and fatigue. ^{3 5 6 7 8}

How do the drugs Anastrozole and Letrozole differ from other breast cancer treatments?

Anastrozole and Letrozole are unique because they are selective, oral, non-steroidal aromatase inhibitors that are more effective and better tolerated than the standard therapy, megestrol acetate, for advanced breast cancer in postmenopausal women. They work by reducing estrogen levels, which is particularly important for women with higher body mass index (BMI), as obesity can affect the efficacy of other treatments like tamoxifen. ^{1 2 5 6 9}

What is the purpose of this trial?

More than three quarter of patients with breast cancer are treated by hormone pills called tamoxifen and aromatase inhibitors (AIs). AIs are drugs that stop female hormone production. This hormone production mostly happens in fat, muscle, and breast tissue in postmenopausal women. The female hormone estrogen is an important hormone for the growth of breast cancer cells. Anastrozole (Arimidex®) and Letrozole (Femara®) are AIs that are approved by the Food and Drug Administration (FDA). They have been used since 2005 to treat women with early stage breast cancer. When given before surgery (neoadjuvant), both anastrozole and letrozole have been shown to successfully shrink breast cancer tumors in most patients. In over 50% of patients, anastrozole and letrozole when given for about 4 months also helped to improve surgery outcomes. On top of that, whether or not a patient responds to anastrozole and letrozole before surgery can help the doctor decide whether that patient needs additional chemotherapy. One of the things may influence the level of hormone is body weight. It has been previously shown that postmenopausal women with higher body fat have higher level of female hormone as well as an increased risk of breast cancer. This is likely due to an increase in aromatase activity in the fatty tissue. However, at the current time AIs are used at the same doses in all women with breast cancer no matter whether they have different body weight. Currently, we do not know for certain whether the same doses of AIs work as well in patients with higher body fat compared to patients with less body fat. The purpose of this study is to see if women with higher body fat respond differently to AI treatment compared to women with lower body fat.

Research Team

Emily C Bellavance, M.D.

Principal Investigator

University of Maryland, Baltimore

Eligibility Criteria

This trial is for postmenopausal women with hormone-sensitive, early-stage breast cancer who haven't had previous treatments for their current condition. They must have a tumor at least 2 cm large and be in good enough health to participate. Women with higher body fat are of particular interest to see if they respond differently to the treatment.

Inclusion Criteria

I am a woman aged 18 or older.

I haven't had chemo, radiation, or hormone therapy for my current breast cancer.

I have a suitable tumor tissue sample for study, not just from a fine needle aspiration.

Exclusion Criteria

I have not had any cancer except breast cancer, skin cancer, or treated cervical cancer in the last 3 years.

I am allergic to medications similar to anastrozole or letrozole.

Patients may not be receiving any other investigational agent.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant treatment with Anastrozole or Letrozole based on BMI, with treatment lasting between 2-4 weeks before surgery

2-4 weeks

Weekly visits for clinical assessment

Extended Treatment

Participants may continue AI treatment up to 18 weeks if beneficial, with clinical assessments every 4-6 weeks

Up to 18 weeks

Bi-weekly visits for clinical assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up for 30 days after the last dose of AI

30 days

Treatment Details

Interventions

• Anastrozole
• Letrozole

Trial Overview The study tests whether overweight or obese women respond differently to Anastrozole (Arimidex®) and Letrozole (Femara®), which are drugs that reduce estrogen production used in early-stage breast cancer treatment. The effectiveness of these drugs may vary based on body fat levels.

Participant Groups

Group I: Cohort 4: Normal Weight Letrozole Active Control 1 Intervention

Cohort 4: Patients with BMI \< 25.0 kg/m2 treating with letrozole

Group II: Cohort 1: Normal Weight Anastrozole Active Control 1 Intervention

Cohort 1: Patients with BMI \< 25.0 kg/m2 treated with anastrozole

Group III: Cohort 2: Overweight Anastrozole Active Control 1 Intervention

Cohort 2: Patients with BMI ≥ 25.0-29.9 kg/m2 treated with anastrozole

Group IV: Cohort 3: Obese Active Control 1 Intervention

Cohort 3: Patients with BMI ≥ 30 kg/m2 treated with anastrozole

Group V: Cohort 5: Overweight Letrozole Active Control 1 Intervention

Cohort 5: Patients with BMI ≥ 25.0-29.9 kg/m2 treating with letrozole

Group VI: Cohort 6: Obese Letrozole Active Control 1 Intervention

Cohort 6: Patients with BMI ≥ 30 kg/m2 treating with letrozole

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 Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

In a study of 370 postmenopausal women with breast cancer undergoing treatment with letrozole, body mass index (BMI) did not significantly affect circulating levels of oestrone sulphate, a form of estrogen.

Despite variations in BMI among the participants, there were no statistically significant differences in estrogen levels, suggesting that obesity may not influence the efficacy of letrozole in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body mass index and circulating oestrone sulphate in women treated with adjuvant letrozole. Sini, V., Lunardi, G., Cirillo, M., et al.[2021]

Overweight premenopausal patients treated with the aromatase inhibitor anastrozole had a 60% higher risk of disease recurrence and more than double the risk of death compared to normal weight patients, indicating that body mass index (BMI) significantly affects treatment outcomes.

The study suggests that BMI may influence the efficacy of anastrozole through mechanisms related to aromatase enzyme availability and the effectiveness of ovarian suppression by goserelin, highlighting the need for personalized treatment approaches based on patient weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. Pfeiler, G., Königsberg, R., Fesl, C., et al.[2022]

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 713 postmenopausal women with advanced breast cancer, letrozole (2.5 mg/day) demonstrated a significantly higher overall response rate (19.1%) compared to anastrozole (1 mg/day) (12.3%), indicating that letrozole may be more effective as a second-line endocrine therapy.

Despite the improved response rate with letrozole, both treatments showed no difference in time to progression, overall survival, or safety profiles, suggesting that while letrozole is more effective in eliciting responses, both drugs are well tolerated and have similar safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open randomised trial of second-line endocrine therapy in advanced breast cancer. comparison of the aromatase inhibitors letrozole and anastrozole. Rose, C., Vtoraya, O., Pluzanska, A., et al.[2022]

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 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]

Letrozole is a new non-steroidal aromatase inhibitor approved in Japan for treating postmenopausal women with breast cancer, particularly effective for those with steroid receptor positive or receptor-unknown locally advanced or metastatic cases.

The drug is generally well-tolerated, with mostly mild side effects such as hot flashes and fatigue, and has shown beneficial results in large international studies for post-surgical endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. Tsukagoshi, S.[2018]

Letrozole, an aromatase inhibitor, significantly reduced plasma estrone by over 86% and estradiol by approximately 67% in 14 postmenopausal women with metastatic breast cancer, indicating its strong efficacy in lowering estrogen levels.

The treatment resulted in a 36% objective response rate, with one complete response and four partial responses, and no significant toxic effects were observed, suggesting that letrozole is a safe and promising option for patients with advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole, a new oral non-steroidal aromastase inhibitor in treating postmenopausal patients with advanced breast cancer. A pilot study. Bisagni, G., Cocconi, G., Scaglione, F., et al.[2020]

In a study of 44 postmenopausal women with early estrogen receptor-positive breast cancer, higher body mass index (BMI) was associated with greater levels of estradiol and estrone sulfate, indicating that BMI may influence the effectiveness of aromatase inhibitors (AIs) like anastrozole and letrozole.

Letrozole was found to suppress estrogen levels more effectively than anastrozole across all BMI ranges, suggesting that it may be a better treatment option for women with higher BMI who are at risk of reduced aromatase inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer. Folkerd, EJ., Dixon, JM., Renshaw, L., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Body mass index and circulating oestrone sulphate in women treated with adjuvant letrozole. [2021]

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

Impact of body mass index on the efficacy of endocrine therapy in premenopausal patients with breast cancer: an analysis of the prospective ABCSG-12 trial. [2022]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

An open randomised trial of second-line endocrine therapy in advanced breast cancer. comparison of the aromatase inhibitors letrozole and anastrozole. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

7. Japan pubmed.ncbi.nlm.nih.gov

[Introduction of new drug: letrozole, a new non-steroidal aromatase inhibitor for the treatment of postmenopausal women with breast cancer]. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Letrozole, a new oral non-steroidal aromastase inhibitor in treating postmenopausal patients with advanced breast cancer. A pilot study. [2020]

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

Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer. [2022]