Adjuvant Ovarian Suppression Plus Aromatase Inhibitor or Tamoxifen in Young Women

Study Overview
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Brief Summary
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The objective of this study is to compare the curative effects in patients under the age of 35 with hormone receptor positive breast cancer and high recurrent risk factors including large tumor or metastatic lymph nodes randomized to ovarian function suppression (OFS) plus aromatase inhibitors or OFS plus tamoxifen as adjuvant endocrine therapy, and explore the differences of curative effects between different subtypes to provide direct evidence for treatments of young breast cancer patients.

Official Title
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Adjuvant Ovarian Suppression Plus Aromatase Inhibitor or Tamoxifen for Hormone Receptor-Positive Breast Cancer in Women Younger Than 35: A Multicenter Randomized Clinical Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Goserelin
* Drug: Tamoxifen
* Drug: Aromatase Inhibitors
* Drug: Leuprolide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2; Patients pathologically diagnosed with hormone receptor positive invasive breast cancer: immunohistochemistry ER positive (≥1%); Premenopausal patients with age ≤35 years (at least menstruate once for prior 3 months, assess menstruation situation before chemotherapy if have); No distant metastasis; Clinical stage (TNM) meets at least one of the conditions as follow: T≥2cm or at least one region of regional lymph node metastasis (including micrometastases); Patients must have undergone a surgery and (neo)adjuvant chemotherapy, targeted therapy, radiotherapy (if necessary) according to Chinese Anti-Cancer Association guidelines and specifications version 2015 for diagnosis and treatment of breast cancer; Indexes of hematology and biochemistry conform to following standards: HGB≥10g/dl, WBC≥4,000/mm3, PLT≥100,000/mm3, GOT, GPT, ALP≤2xULN, TBIL, DBIL, CCr≤1.5xULN. Exclusion Criteria: Pregnant or lactating women or women of childbearing potential reject contraceptive measures; History of organ transplantation (including autologous bone marrow transplantation and peripheral stem cell transplantation); Concurrent malignancies or history of non-breast malignancies within the 5 years prior to study entry, except for curatively treated basal cell and squamous cell carcinomas of the skin, carcinoma in situ of the cervix; peripheral nervous system disorders caused by diseases or history of obvious mental and central nervous system disorders; Prior use of neo-adjuvant chemotherapy after a definite diagnosis; Nervous system disorders caused by diseases or obvious mental disorder, which would affect patients right to consent and compliance, or make patients in critical condition; Serious hepatopathy (e.g., cirrhosis, etc.), nephropathy, respiratory illness, digestive illness or poorly controlled diabetes; Cardiac illness with obvious abnormal EKG or clinical symptoms, namely congestive heart failure, coronary atherosclerotic heart disease with obvious symptoms, arrhythmia difficult to control by drugs, or history of myocardial infarction within the 12 months prior to study entry or class III/IV of cardiac function; Concurrent treatment in another investigational trial; Sensitivity or contraindication to any of the study medications.

Ages Eligible for Study
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Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ovarian Suppression and aromatase inhibitors<br>Ovarian Suppression：Goserelin 3.6 mg or Leuprolide 3.75 mg administered intravenously every 28 days, for 5 years. AI: no restriction of specific drugs, oral by standard dose of post-menopause breast cancer, for 5 years. | Drug: Goserelin<br> <br> Drug: Aromatase Inhibitors<br> <br> Drug: Leuprolide<br> <br> * Other names: leuprolide acetate;|
| Active Comparator: Ovarian Suppression and tamoxifen<br>Ovarian Suppression：Goserelin 3.6 mg or Leuprolide 3.75 mg administered intravenously every 28 days, for 5 years. Tamoxifen: 20mg oral for every day, for 5 years. | Drug: Goserelin<br> <br> Drug: Tamoxifen<br> <br> Drug: Leuprolide<br> <br> * Other names: leuprolide acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-Free Survival (DFS) | DFS is defined as the time between randomization and the date of the first occurrence of events as follow: local, regional recurrence or distant metastasis of invasive breast cancer, contralateral invasive breast cancer, or death due to any diseases. Patients who have not had disease progression or death at the end of follow-up (5 years) will be censored at the date last known to be alive and distant metastasis free. Subgroup analysis DFS of Luminal A and Luminal B breast cancer. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The time from randomization to death due to any cause. Patients still alive at the end of follow-up (5 years) will be censored at the last known alive date. | 5 years | 
| Invasive Breast Cancer Recurrence-Free Interval（BCFI) | The time between randomization and the first occurrence of local, regional recurrence or distant metastasis of invasive breast cancer, or contralateral invasive breast cancer. Patients who have not had invasive breast cancer recurrence at the end of follow-up (5 years) will be censored at the date last known to be distant metastasis free. | 5 years | 
| Adverse Effects Rate |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, ovarian function suppression (OFS), aromatase inhibitors（AIs）, tamoxifen（TAM）