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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how different body weights in postmenopausal women with breast cancer affect the success of hormone-blocking treatments called aromatase inhibitors (AIs). Specifically, it examines whether overweight or obese women respond differently to AIs like anastrozole (Arimidex) and letrozole (Femara) compared to women with normal body weight. Participants are grouped based on body mass index (BMI) and receive a specific AI to determine if weight impacts treatment effectiveness. Women diagnosed with hormone-sensitive breast cancer who have not received prior treatment for this cancer may be suitable for this trial. As an unphased trial, this study provides a unique opportunity to contribute to understanding how body weight influences treatment success, potentially benefiting future patients.

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.

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

Studies have shown that anastrozole and letrozole have been safely used for many years to treat breast cancer. The FDA has approved these drugs, indicating they have passed strict safety tests for treating early-stage breast cancer.

Since 2005, anastrozole has been generally well-tolerated, according to research. However, some patients, particularly those who are overweight, might experience more joint-related side effects. These side effects can be uncomfortable but are usually not severe.

Letrozole is also well-studied and generally safe. Research suggests that being overweight does not affect how women respond to letrozole, allowing women with higher body weight to safely use this treatment.

Both treatments work by blocking estrogen, a hormone that can help cancer grow. They have been shown to shrink tumors in many patients before surgery, aiding doctors in planning the best treatment path. While side effects can occur, they are often manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using aromatase inhibitors like Anastrozole and Letrozole for breast cancer in overweight and obese women because these treatments target estrogen production, which is crucial in hormone-receptor-positive breast cancer. Typically, current treatments focus on blocking estrogen receptors, but these inhibitors stop estrogen production altogether, offering a different approach. Additionally, by tailoring treatment based on body mass index (BMI), there is potential to optimize effectiveness, as body fat can influence hormone levels. This personalized approach could lead to better outcomes for patients with different BMI categories.

What is the effectiveness track record for anastrozole and letrozole in treating breast cancer?

Studies have shown that both anastrozole and letrozole effectively treat early-stage breast cancer. These drugs, known as aromatase inhibitors (AIs), reduce estrogen, a hormone that can promote breast cancer cell growth. Used before surgery, they have successfully shrunk tumors and improved surgical outcomes for more than half of the patients. This trial will assess the effectiveness of anastrozole and letrozole across different body weight categories. Research indicates that obesity can influence AI effectiveness, as more body fat can increase estrogen production. However, evidence shows that obesity does not necessarily worsen outcomes for patients taking letrozole. While treatment effectiveness may vary with body weight, these drugs remain crucial in breast cancer care. ^{6 7 8 9 10}

Who Is on the Research Team?

Emily C Bellavance, M.D.

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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, 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]

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]

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]

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]

Citations

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Body composition changes during breast cancer ... BMI group was defined as underweight (<18.5 kg/m2), healthy weight (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30.0 kg/m2).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12214061/

significance of the BIG 1–98 and ATAC trial data Similarly preclinical models demonstrate that diet-induced obesity in mice reduces letrozole sensitivity, with tumors in obese mice showing 30% ...

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Does Obesity Interfere With Anastrozole Treatment ... Omega-3 fatty acid use for obese breast cancer patients with aromatase inhibitor-related arthralgia (SWOG S0927). 2018, Breast Cancer Research and Treatment ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2009.27.2021

Effect of Body Mass Index on Recurrences in Tamoxifen ... It is well known that postmenopausal women who are overweight/obese have an increased risk of developing breast cancer, and a few studies have ...

5. uspharmacist.com uspharmacist.com/article/obesity-bc-recurrence-in-patients-on-aromatase-inhibitors

Obesity, BC Recurrence in Patients on Aromatase Inhibitors At the time of BC diagnosis, 14.4% of patient were obese, 6.5% had severe obesity, and almost one-third (32.5%) were overweight. Patients who ...

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Long-term efficacy and safety of anastrozole for adjuvant ... In multiple logistic regression analysis, being overweight (BMI 25 to 30 kg/m2) and prior tamoxifen therapy were inversely associated with AI-related joint ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405457725002918

Body mass index and clinical outcomes in breast cancer ... However, it is noteworthy that overweight and obese patients exhibit an increased incidence of immune-related adverse events (irAEs) [32]. In the context of ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2016.69.2871

Comparative Efficacy and Safety of Adjuvant Letrozole ... In the ATAC trial, anastrazole seemed less effective in postmenopausal women who were obese, possibly reflecting its incomplete suppression of ...

9. nature.com nature.com/articles/bjc2013367

an analysis of the randomised ABCSG-6a trial Obesity has an independent prognostic value regarding breast cancer. It has been demonstrated that overweight and obese patients experience a ...

10. aacrjournals.org aacrjournals.org/clincancerres/article/30/15/3147/746579/Anastrozole-Dose-Escalation-for-Optimal-Estrogen

Anastrozole Dose Escalation for Optimal Estrogen ... BMI is known to have an impact on breast cancer risk and prognosis, and obese postmenopausal women are at increased risk for breast cancer ...