Pre-Surgery Endocrine Therapy for Breast Cancer

Overseen By Komal Jhaveri, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Endocrine therapy

Disqualifiers: History of breast cancer, Stage IV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how pre-surgery endocrine therapy (also known as hormone therapy) affects a protein called Ki67 in patients with ER+/HER2- breast cancer. The researchers seek to determine if Ki67 changes differ between those with the BRCA2 mutation and those without it. Participants will receive endocrine therapy for at least two weeks before their scheduled surgery. The trial seeks postmenopausal women with stage I-III ER+/HER2- breast cancer who are already scheduled for surgery and eligible for genetic testing. As an unphased trial, this study offers a unique opportunity to contribute to understanding personalized treatment effects in breast cancer.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that hormone therapy for breast cancer is generally safe. Many patients tolerate aromatase inhibitors, such as anastrozole, letrozole, and exemestane, well. However, some experience side effects like muscle and joint pain. These side effects occur at different rates with each drug, with anastrozole reported most frequently, followed by exemestane and letrozole.

One study found that prolonged hormone therapy can increase the risk of bone fractures. However, the same study showed that the therapy continues to significantly lower the risk of dying from breast cancer over time.

In summary, while some side effects exist, research strongly supports the benefits of hormone therapy in reducing the risk of death from breast cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this treatment protocol because it aims to integrate pre-surgery endocrine therapy with the ability to quickly assess how well it works using tumor markers. Unlike standard treatments that may take longer to provide information, this approach allows for an early evaluation of cancer cell activity through Ki67 testing and Oncotype results. These insights can help tailor post-surgical treatments more effectively and potentially reduce the time to start any necessary chemotherapy. Ultimately, this could lead to more personalized and timely treatment plans for breast cancer patients.

What evidence suggests that endocrine therapy might be an effective treatment for breast cancer?

Research shows that hormone therapy can help lower the risk of breast cancer recurrence. In this trial, all participants will receive standard endocrine therapy (ET) before surgery. Studies have found that taking tamoxifen for 5 years can reduce the chance of cancer returning by 40% and lower the risk of death by 30%. Aromatase inhibitors, another type of hormone therapy, also improve outcomes, particularly for younger women. For instance, women under 45 experienced a significant decrease in new cancer cases. Extending hormone therapy from 5 to 10 years can further reduce the risk of cancer returning. Overall, hormone therapy is a proven method for managing ER+ (estrogen receptor-positive) breast cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Minna Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for women over 18 with stage I-III ER+/HER2- invasive breast cancer, scheduled for surgery and eligible for genetic testing. It's not open to those with a history of breast cancer, recent endocrine therapy for risk reduction, stage IV disease at presentation, or if pregnant.

Inclusion Criteria

I am eligible for genetic testing based on national cancer guidelines.

I am scheduled for an initial surgery soon.

I am a woman over 18 with early to mid-stage breast cancer that is ER+ and HER2-.

Exclusion Criteria

Pregnant

My condition was diagnosed at stage IV.

I have had breast cancer in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive at least 2 weeks of endocrine therapy before surgery

2 weeks

Surgery

Participants undergo cancer removal surgery and tumor tissue is assessed for Ki67 expression

Follow-up

Participants are monitored for safety and effectiveness after surgery

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Endocrine Therapy

Trial Overview The study examines the effect of endocrine therapy before surgery on Ki67 expression in breast tissue. Researchers will compare changes between BRCA2 mutation carriers and noncarriers after at least two weeks of treatment.

How Is the Trial Designed?

Group I: Breast Cancer Experimental Treatment 2 Interventions

All study patients will receive standard ET for at least 2 weeks. In accordance with the standard of care, postmenopausal women will receive AI (anastrazole 1mg daily tablet, letrozole 2.5mg daily tablet, or exemestane 25mg daily tablet Which will be followed by standard of care surgical treatment. Surgical tumor tissue will be obtained at the time of surgery and will be assessed for Ki67; a portion of this specimen will be snap-frozen for future analysis. In collaboration with the surgical team, Oncotype can be sent on this research biopsy after pathology assessment. This will enable the patient to receive the Oncotype result and to gain knowledge on the recommendation for adjuvant chemotherapy about 4-6 weeks earlier than our normal workflow.

Endocrine Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in United States as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Canada as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Japan as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in China as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Switzerland as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

Endocrine therapy is crucial for treating endocrine-sensitive breast cancer, significantly lowering recurrence rates and mortality when administered for 5 years in the adjuvant setting.

Tamoxifen is preferred for premenopausal women, while aromatase inhibitors are standard for postmenopausal women; however, managing side effects is essential to ensure patient compliance and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Endocrine therapy in breast cancer: efficacy and adverse events]. Odermatt, R., Wolfer, A., Zaman, K.[2013]

Tamoxifen, while a long-standing treatment for early breast cancer, only prevents about half of relapses and can lead to serious side effects like endometrial hyperplasia and venous thromboembolism due to its estrogenic activity.

Aromatase inhibitors are emerging as a more effective alternative, showing benefits in various treatment settings, including extending therapy after tamoxifen and providing upfront adjuvant therapy, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant endocrine therapy in breast cancer. Management of early-risk relapse]. Chahine, G., Howayek, M., Atallah, D.[2013]

Endocrine therapy is a key treatment for metastatic breast cancer, offering effective and minimally toxic options, with tamoxifen being the preferred first-line therapy for both premenopausal and postmenopausal women.

Research is ongoing to develop new 'pure' antiestrogens and to combine endocrine therapy with biologic agents, which may enhance treatment effectiveness in both early and advanced stages of breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy in metastatic breast cancer. Kimmick, GG., Muss, HB.[2019]

Endocrine therapy is a highly effective and well-tolerated treatment for hormone receptor positive metastatic breast cancer, showing survival rates comparable to chemotherapy, making it the preferred initial treatment except in cases of rapid disease progression.

There are multiple options for endocrine therapy available for both premenopausal and postmenopausal women, and ongoing research is needed to optimize its use before considering chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy in metastatic breast cancer: a closer look at the current clinical practice. Ebrahim, H.[2016]

Neoadjuvant endocrine therapy using aromatase inhibitors has shown greater success than tamoxifen in reducing tumor volume in postmenopausal women with estrogen receptor-positive breast cancer, allowing for more surgical options.

The effectiveness of neoadjuvant therapy is linked to estrogen receptor expression levels, with higher expression correlating with better responses and tumor shrinkage, and early research suggests that reduced cell proliferation after 14 days of treatment may serve as a biomarker for response to tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of endocrine therapy in the neoadjuvant surgical setting. Dixon, JM.[2022]

Endocrine therapy is essential for treating premenopausal women with early-stage hormone receptor-positive breast cancer, but there is still uncertainty about the best strategies for using tamoxifen and estrogen deprivation alongside chemotherapy.

Research is ongoing to find better markers for predicting how well patients will respond to endocrine therapy and to understand the unique side effects that young women may experience from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for premenopausal women with breast cancer. Brown, RJ., Davidson, NE.[2015]

Pre-operative endocrine therapy is now recognized as a valuable treatment option for postmenopausal women with estrogen receptor-positive (ER+) breast cancer, helping to down-stage large or locally advanced tumors before surgery.

Recent advancements include the use of dual endocrine targeting and combinations with other targeted therapies, which may improve long-term outcomes and provide important prognostic information for managing ER+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-operative Endocrine Therapy. Arthur, LM., Turnbull, AK., Khan, LR., et al.[2022]

Endocrine therapy for breast cancer has evolved significantly, with a wide range of medical treatments now available that can effectively prolong survival in advanced stages, while being curative in early disease.

Recent advancements include new antiestrogens, aromatase inhibitors, and targeted therapies that utilize biological factors to personalize treatment, allowing for better selection of patients and treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel endocrine therapies in breast cancer. Klijn, JG., Setyono-Han, B., Bontenbal, M., et al.[2019]

Adjuvant endocrine treatment is crucial for postmenopausal women with hormone receptor-positive breast cancer, with options including tamoxifen and aromatase inhibitors, each having unique side effects.

For premenopausal women, tamoxifen is the standard treatment, and ongoing research is exploring the potential benefits of adding ovarian suppression to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for early-stage breast cancer. Burstein, HJ., Griggs, JJ.[2010]

Preoperative endocrine therapy for ER-positive breast cancer can achieve a response rate of nearly 70% within about 3 months, offering a less toxic alternative to neoadjuvant chemotherapy, which has no demonstrated survival benefit over adjuvant therapy.

Further randomized clinical trials are needed to establish the effectiveness of preoperative endocrine therapy compared to traditional adjuvant therapy, determine the optimal treatment duration, and identify additional predictive factors for patient response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative endocrine therapy for breast cancer. Cheung, KL., Howell, A., Robertson, JF.[2019]

Endocrine therapy, particularly with tamoxifen and newer agents like aromatase inhibitors, is effective for treating hormone-sensitive breast cancer, providing a more tolerable treatment option for patients.

Neoadjuvant endocrine therapy is gaining recognition for its potential benefits in treating initially inoperable locally advanced breast cancers, with clinical assessments helping predict future treatment responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neoadjuvant endocrine therapy for breast cancer: an overview]. Domont, J., Namer, M., Khayat, D., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10453164/

Extended Adjuvant Endocrine Therapy in Early Breast ... Taking tamoxifen for 5 years has been shown to reduce the risk of breast cancer recurrence by 40% and mortality by 30% compared to patients ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)01013-X/fulltext

Extending the duration of endocrine treatment for early ... The corresponding proportional reductions in breast cancer mortality rates are about 30% and 40%, and continue beyond year 10. Even after ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2104162

Duration of Adjuvant Aromatase-Inhibitor Therapy in ... No between-group difference was noted for overall survival at 8 years (87.5% in the 2-year group and 87.3% in the 5-year group), with a hazard ...

4. nature.com nature.com/articles/s41523-025-00746-7

Impact of endocrine therapy regimens for early-stage ER+ ... For the 5-year aromatase inhibitors therapy, women <45 years had the largest reduction in CBC cases (5.0/100), which dropped to 2.7/100 for ...

5. esmoopen.com esmoopen.com/article/S2059-7029(25)00926-3/fulltext

Extended adjuvant endocrine therapy in early breast cancer 10 years of adjuvant ET is superior to 5 years in reducing recurrences. Seven to eight years of ET improves outcomes compared with 5 years.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17890211/

Safety profiles of tamoxifen and the aromatase inhibitors in ... Tamoxifen has been used as adjuvant therapy for early breast cancer for many years, and safety data have been well documented, but a poor risk:benefit profile ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225000027

Safety of topical estrogen therapy during adjuvant ... The present study suggests that TE exposure of breast cancer survivors on TAM or AI did not appear to increase mortality risk. Concurrent use of TAM and TE did ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.1051

Aromatase inhibitors for breast cancer therapy: Analysis of ... MSK AEs were mostly reported with anastrozole, followed by exemestane, and letrozole in 35.23%, 33.97%, and 32.06%, respectively (P < 0.001).