Symptom Monitoring for Young Women on Hormone Therapy for Breast Cancer

Recruiting at 489 trial locations

Overseen by Norah L Henry

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: Southwest Oncology Group

Must be taking: Oral endocrine therapy

Must not be taking: Oral estrogen, Progesterone

Disqualifiers: Metastatic cancer, Pregnancy, others

No Placebo Group

Approved in 5 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase III trial compares the effect of active symptom monitoring and patient education to patient education alone in helping young women with stage I-III breast cancer stay on their hormone therapy medicines. The patient education tool contains interactive weblinks which provide patients with education material about breast cancer and side effects of therapy. Symptom monitoring is a weblink via email or text message with questions asking about symptoms. Hormone therapy for breast cancer can cause side effects, and may cause some women to stop treatment early. Asking about symptoms more often may help women keep taking hormone therapy medicines.

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

The trial does not specify if you need to stop taking your current medications, but you must not take oral estrogen or progesterone treatments during the study. You should continue your hormone therapy for breast cancer as part of the trial.

What data supports the effectiveness of hormone therapy drugs like tamoxifen, anastrozole, exemestane, and letrozole for breast cancer?

Research shows that hormone therapy drugs like tamoxifen and third-generation aromatase inhibitors (anastrozole, exemestane, and letrozole) are effective in treating hormone-sensitive breast cancer in postmenopausal women. These drugs have been shown to improve disease-free survival and are often more effective than tamoxifen alone, especially in advanced breast cancer settings. ^{1 2 3 4 5}

Is hormone therapy for breast cancer safe for young women?

Hormone therapies like letrozole, anastrozole, and exemestane are generally well-tolerated, but they can cause side effects such as hot flushes, joint pain, and an increased risk of fractures. There is also a potential risk of cardiovascular issues, with letrozole showing a higher risk compared to others, but none of these therapies showed a lower risk of cardiovascular events compared to tamoxifen, except for thromboembolism. ^{6 7 8 9 10}

How is hormone therapy for breast cancer different from other treatments?

Hormone therapy for breast cancer, including drugs like tamoxifen and aromatase inhibitors (anastrozole, letrozole, exemestane), works by blocking or lowering estrogen, which fuels some breast cancers. This approach is different from chemotherapy, which kills cancer cells directly, and is often used for hormone-sensitive breast cancers, offering a targeted treatment with potentially fewer side effects. ^{5 7 11 12 13}

Research Team

Norah L Henry

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

This trial is for young women aged 18 or older with Stage I-III hormone receptor positive breast cancer. They must have completed chemotherapy, surgery, and started or plan to start standard oral endocrine therapy. Participants need to be pre- or peri-menopausal at diagnosis and able to complete surveys in English or Spanish. Exclusions include current treatment for non-breast malignancies, prior aromatase inhibitor therapy, metastatic cancer, use of estrogen/progesterone treatments during the study, pregnancy plans within 80 weeks of study participation.

Inclusion Criteria

I had breast cancer surgery at least 14 days ago.

If you are a woman, you were still having regular menstrual periods or had hormone levels consistent with premenopausal status before or shortly after being diagnosed with breast cancer.

Participants must be offered the opportunity to participate in specimen banking for translational medicine. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) specimen tracking system

Exclusion Criteria

I have never taken tamoxifen for breast cancer before.

I am not currently being treated for cancer outside of my breast.

I have not previously taken aromatase inhibitors for breast cancer.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive endocrine therapy (ET) and standard of care clinic visits with a cancer provider at specified intervals. In Arm I, participants also undergo active symptom monitoring.

72 weeks

Clinic visits at 12, 24, 36, 48, 60, and 72 weeks; phone visit at 80 weeks

Symptom Monitoring

In Arm I, participants are asked 6 brief questions about symptoms weekly by email, text, or phone call for the first 6 months, then every 4 weeks for 12 months.

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including optional blood specimen collection.

6 months

Treatment Details

Interventions

• Hormone Therapy (Hormone Therapy)

Trial Overview The ASPEN Study is testing whether active symptom monitoring plus patient education helps young women continue their hormone therapy compared to patient education alone. The intervention includes a web-based symptom assessment tool and educational material about managing side effects from hormone therapy medicines.

Participant Groups

Group I: ARM I (ET, health education, symptom assessment) Experimental Treatment 6 Interventions

Patients receive ET and standard of care clinic visits with a cancer provider at 12, 24, 36, 48, 60, and 72 weeks, and phone visit at 80 weeks to access ongoing use ET medication. Patients are asked 6 brief questions about symptoms weekly by email, text, or phone call for the first 6 months, then every 4 weeks for 12 months. Patients also receive a list of websites with information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health. Patients have the option to submit blood specimen collection at baseline, 3, 12, and 18 months.

Group II: ARM II (ET, health education) Active Control 5 Interventions

Patients receive ET and standard of care clinic visits with a cancer provider at 12, 24, 36, 48, 60, and 72 weeks, and phone visit at 80 weeks to access ongoing use ET medication. Patients also receive a list of websites with information about breast cancer, side effects of breast cancer medicines, and ways to help with heart health. Patients have the option to submit blood specimen collection at 3, 12, and 18 months.

Hormone Therapy is already approved in Canada, Japan, Switzerland for the following indications:

Approved in Canada as Hormone Therapy for:

• Breast cancer
• Hormone receptor-positive breast cancer

Approved in Japan as Hormone Therapy for:

• Breast cancer
• Hormone receptor-positive breast cancer

Approved in Switzerland as Hormone Therapy for:

• Breast cancer
• Hormone receptor-positive breast cancer

Who Is Running the Clinical Trial?

Southwest Oncology Group

Lead Sponsor

Trials

389

Recruited

260,000+

Dr. Lyudmila Bazhenova

Southwest Oncology Group

Chief Medical Officer since 2021

MD from University of California, San Diego

Dr. Richard Schilsky

Southwest Oncology Group

Chief Executive Officer since 2013

MD from University of California, San Diego

SWOG Cancer Research Network

Lead Sponsor

Trials

403

Recruited

267,000+

Dr. Charles D. Blanke

SWOG Cancer Research Network

Chief Executive Officer since 2012

MD from Oregon Health & Science University

Dr. Dawn Hershman

SWOG Cancer Research Network

Chief Medical Officer since 2020

MD from Columbia University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Third-generation aromatase inhibitors, such as letrozole, anastrozole, and exemestane, are effective and well-tolerated treatments for postmenopausal women with hormone-sensitive metastatic or locally advanced breast cancer.

These inhibitors are not only beneficial as first or second-line treatments but also serve as valuable options in neoadjuvant therapy and for localized tumors in women who cannot undergo surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary hormone treatment in postmenopausal women with breast cancer. Maciá Escalante, S., Pons Sanz, V., Rodríguez Lescure, A., et al.[2019]

Letrozole, a third-generation aromatase inhibitor, effectively lowers estrogen levels in postmenopausal women and has been shown to be more effective than tamoxifen in treating hormone-receptor-positive early breast cancer.

Clinical trials indicate that letrozole significantly improves disease-free survival, particularly in high-risk patients, making it a crucial option in adjuvant therapy for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on the use of letrozole in breast cancer. Wu, M., Goss, PE.[2019]

Letrozole, an aromatase inhibitor, has been shown to be significantly more effective than tamoxifen in treating advanced breast cancer, particularly in terms of median time to progression and response rates, while being well tolerated by patients.

Anastrozole and exemestane also provide effective alternatives to tamoxifen, with anastrozole showing equivalent efficacy overall but superior results in hormone receptor-positive patients, and exemestane demonstrating better response rates, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors in advanced breast cancer. Mouridsen, HT.[2019]

Third-generation aromatase inhibitors (AIs) like anastrozole, exemestane, and letrozole have shown superior efficacy compared to tamoxifen in treating hormone-receptor-positive breast cancer in postmenopausal women, particularly in neoadjuvant and adjuvant settings.

Letrozole, when used as extended adjuvant therapy after 5 years of tamoxifen, significantly improved disease-free survival and overall survival in node-positive patients, highlighting its effectiveness in long-term treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The breast cancer continuum in hormone-receptor-positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors. Rugo, HS.[2022]

Recent trials indicate that third-generation aromatase inhibitors (AIs) like anastrozole and letrozole are at least as effective, and possibly more effective, than tamoxifen for treating metastatic breast cancer, with improved response rates and time to progression.

In a study of 1021 patients, anastrozole showed a slightly better overall response rate (29% vs. 26%) and significantly improved time to progression (8.5 months vs. 7.0 months) compared to tamoxifen, while letrozole demonstrated even greater improvements in response rate (30% vs. 20%) and clinical benefit (49% vs. 38%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of tamoxifen and aromatase inhibitors/inactivators in postmenopausal patients. Pritchard, KI.[2013]

In a network assessment of third-generation aromatase inhibitors (AIs) for postmenopausal estrogen receptor-positive breast cancer, letrozole was associated with the highest risk of severe cardiovascular (CV) events, followed by exemestane and anastrozole.

None of the AIs demonstrated a lower risk of cardiovascular events compared to tamoxifen, except for a lower incidence of thromboembolism, suggesting that while AIs are effective treatments, they may carry significant cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: a network meta-analysis. Zhao, X., Liu, L., Li, K., et al.[2020]

In a study of 686 postmenopausal women with early breast cancer, both anastrozole and exemestane showed comparable treatment-related symptoms (TRS) and health-related quality of life (HRQL) over 5 years, indicating similar tolerability between the two aromatase inhibitors.

However, a significant burden of TRS was linked to poorer HRQL, and women who experienced more side effects before starting treatment were more likely to discontinue therapy early, highlighting the importance of managing side effects to improve treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Wagner, LI., Zhao, F., Goss, PE., et al.[2023]

In a study of 3887 post-menopausal patients with hormone receptor-positive early breast cancer, over 85% persisted with letrozole treatment for 12 months, but 14.6% discontinued, primarily due to side effects.

Musculoskeletal symptoms and sleep disorders were the most significant adverse events leading to treatment discontinuation, with hazard ratios of 2.55 and 1.95, respectively, indicating a strong need for targeted compliance programs to support patients experiencing these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study. Nabieva, N., Fehm, T., Häberle, L., et al.[2022]

Letrozole, a nonsteroidal aromatase inhibitor, has been found to be superior to tamoxifen in treating metastatic breast cancer, indicating its potential to replace tamoxifen in various treatment scenarios.

The review highlights the need for further clinical studies to compare the risks and benefits of letrozole and tamoxifen for new indications, particularly in adjuvant therapy for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole in the treatment of breast cancer. Shaw, HS., Ellis, MJ.[2019]

Letrozole, a type 2 aromatase inhibitor, effectively reduces estrogen levels in postmenopausal women, leading to improved disease-free survival in breast cancer patients compared to other treatments like tamoxifen.

The drug is generally well-tolerated, though it may cause side effects such as hot flushes, joint pain, and a potential increased risk of fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: advancing hormone therapy in breast cancer. Lee, RJ., Armstrong, AC., Wardley, AM.[2018]

Aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane are effective adjuvant therapies for postmenopausal women with hormone receptor-positive invasive breast cancer, showing similar overall survival rates compared to tamoxifen.

While AIs have acceptable toxicity profiles with fewer endometrial cancers and thromboembolic events, they are associated with a higher risk of bone fractures and joint pain compared to tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations. Carlson, RW., Hudis, CA., Pritchard, KI.[2019]

Tamoxifen is the standard treatment for postmenopausal women with hormone-sensitive early breast cancer, but it has side effects that have led researchers to look for safer alternatives.

Third-generation aromatase inhibitors like anastrozole, letrozole, and exemestane have shown better efficacy and a more favorable side effect profile compared to tamoxifen in randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. Grana, G.[2018]

Letrozole, a third-generation aromatase inhibitor, has emerged as a significant advancement in hormonal therapy for postmenopausal women with hormone-sensitive early breast cancer, showing improved efficacy compared to the traditional treatment with Tamoxifen.

Recent trials indicate that letrozole offers distinct pharmacokinetic and pharmacodynamic advantages, along with a different side effect profile, which may enhance treatment outcomes for patients compared to other hormonal agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: present and future role in the treatment of breast cancer. Amar, S., Roy, V., Perez, EA.[2019]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Primary hormone treatment in postmenopausal women with breast cancer. [2019]

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

Update on the use of letrozole in breast cancer. [2019]

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

Aromatase inhibitors in advanced breast cancer. [2019]

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

The breast cancer continuum in hormone-receptor-positive breast cancer in postmenopausal women: evolving management options focusing on aromatase inhibitors. [2022]

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

The role of tamoxifen and aromatase inhibitors/inactivators in postmenopausal patients. [2013]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Comparative study on individual aromatase inhibitors on cardiovascular safety profile: a network meta-analysis. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

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]

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

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Letrozole in the treatment of breast cancer. [2019]

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

Letrozole: advancing hormone therapy in breast cancer. [2018]

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

Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations. [2019]

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

Adjuvant aromatase inhibitor therapy for early breast cancer: A review of the most recent data. [2018]

13. England pubmed.ncbi.nlm.nih.gov

Letrozole: present and future role in the treatment of breast cancer. [2019]