Pre-Surgery Endocrine Therapy for Breast Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Minna Lee, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Endocrine therapy

Disqualifiers: History of breast cancer, Stage IV, others

No Placebo Group

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

The researchers are doing this study to look at changes in Ki67 expression after at least 2 weeks of endocrine therapy in people with ER+/HER2- breast cancer undergoing cancer removal surgery. Participants will receive the endocrine therapy before their surgery. The researchers will look at how changes in Ki67 expression compare between participants who are carriers of the BRCA2 mutation and participants who are noncarriers of the BRCA2 mutation.

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.

What data supports the effectiveness of the treatment Endocrine Therapy, Hormone Therapy for breast cancer?

Endocrine therapy is effective for hormone-sensitive breast cancer, helping to shrink tumors before surgery and improve outcomes. It is well-tolerated and can be as effective as chemotherapy for certain types of breast cancer, especially in postmenopausal women. ^{1 2 3 4 5}

Is pre-surgery endocrine therapy for breast cancer safe?

Endocrine therapy, including treatments like tamoxifen and aromatase inhibitors, is generally safe for breast cancer patients, but it can have side effects such as an increased risk of endometrial hyperplasia (thickening of the uterus lining) and venous thromboembolism (blood clots). It's important to monitor and manage these side effects to maintain treatment compliance and improve outcomes. ^{2 3 6 7 8}

How is pre-surgery endocrine therapy for breast cancer different from other treatments?

Pre-surgery endocrine therapy for breast cancer is unique because it can shrink tumors before surgery, making them easier to remove and potentially allowing for breast-conserving surgery instead of a mastectomy. Unlike chemotherapy, it has fewer side effects and can be continued throughout the surgery period, especially benefiting postmenopausal women with estrogen receptor-positive tumors. ^{1 2 9 10 11}

Research Team

Minna Lee, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

My condition was diagnosed at stage IV.

Pregnant

I have had breast cancer in the past.

Trial Timeline

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

Treatment Details

Interventions

• Endocrine Therapy (Hormone 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.

Participant Groups

Group I: Breast Cancer Experimental Treatment 2 Interventions

All study patients will receive standard ET for at least 2 weeks, 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.

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

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+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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 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]

References

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

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

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

Pre-operative Endocrine Therapy. [2022]

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

Adjuvant hormonal therapy for premenopausal women with breast cancer. [2015]

4. France pubmed.ncbi.nlm.nih.gov

[Neoadjuvant endocrine therapy for breast cancer: an overview]. [2018]

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

Endocrine therapy in metastatic breast cancer. [2019]

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

Adjuvant hormonal therapy for early-stage breast cancer. [2010]

7. Lebanon pubmed.ncbi.nlm.nih.gov

[Adjuvant endocrine therapy in breast cancer. Management of early-risk relapse]. [2013]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[Endocrine therapy in breast cancer: efficacy and adverse events]. [2013]

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

Preoperative endocrine therapy for breast cancer. [2019]

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

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

11. England pubmed.ncbi.nlm.nih.gov

Novel endocrine therapies in breast cancer. [2019]