A Randomized ,Open Label Study Comparing the Efficacy of Zoladex® Combined With Arimidex® for 3-2 Years After Selective Estrogen Receptor Modulators (SERMs) as an Adjuvant Therapy for 2-3 Years Versus Continuing Tamoxifen up to 5 Years for Premenopausal Early Breast Cancer Patients With Hormone Receptor Positive, Lymph Node Positive or Tumor≥ 4cm.
Overview
- Phase
- Phase 3
- Intervention
- Zoladex+AI
- Conditions
- Breast Cancer
- Sponsor
- Fudan University
- Enrollment
- 670
- Locations
- 1
- Primary Endpoint
- DFS
- Last Updated
- 14 years ago
Overview
Brief Summary
The present study is a randomized open-label -phase III study that aims to compare the efficacy of Zoladex® combined with Aromidex® for 3-2 years after SERMs (tamoxifen and Fareston®) as an adjuvant therapy for 2-3 years with the efficacy of tamoxifen up to 5 years for premenopausal breast cancer women with hormone receptor positive, lymph node positive or tumor ≥4cm. According to St. Gallen's guideline, hormone receptor positive was defined as endocrine responsive and endocrine response uncertain categories (table 3-1), and only those with ER or PR expression undetectable were considered as HR negative. The pathological evaluation of axillary lymph node could be done by sentinel node biopsy (SNB) when axillary nodes were clinically impalpable accompanied with axillary lymph node dissection (ALND) or directly through ALND when axillary nodes appeared to be positive in clinical examination. Based on the operating standard of local medical institution, identifying the numbers of lymph nodes to do the pathological evaluation and to do the dissection of I- or II-station nodes accurately.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All patients must have signed and dated an informed consent form
- •Patients must be female
- •Primary invasive breast cancer pathologically approved by core needle or open biopsy
- •Ipsilateral axillary or internal mammary nodes positive, or tumor size is equal to or larger than 4cm. Definition of nodes positive is according to the staging system of AJCC 6th edition (American Joint Cancer Commission) for breast carcinoma. The micrometastasis must be at least 0.2mm
- •Patients must have undergone standard surgery for primary breast cancer as shown in the following:
- •a standard radical mastectomy or modified mastectomy
- •standard breast conservation surgery (BCS), which is lumpectomy or qaudrantectomy accompany with axillary dissection, and the surgical margins of the resected specimen must be negative. BCS must be followed by standardized adjuvant radiotherapy to the partial conserved breast (delivered after adjuvant chemotherapy completed)
- •Treatment for confirmed breast cancer including the surgery modality listed above, loco-regional radiotherapy after lumpectomy, adjuvant radiotherapy to the chest wall and/or internal mammary nodes and/or supraclavicular lymph nodes, adjuvant chemotherapy
- •adjuvant endocrine therapy of TAM or Fareston must be started within 6 weeks when adjuvant chemotherapy or radiotherapy was finished
- •The date of randomization must be processed after taking TAM or Fareston for 2 or more than 2 years, but not more than 3 years of time
Exclusion Criteria
- •patients with metastatic malignant tumor
- •previous history of asynchronous bilateral breast cancer
- •any previous malignancy in the past 5 years, except for those treated with curative intent, such as carcinoma in situ of the cervix, squamous carcinoma of the skin or basal cell carcinoma of the skin
- •any non-malignant systemic disease which interfere long time follow up
- •history of medical ovarian ablation therapy
- •history of AI therapy
- •severe live dysfunction, Child-Pugh is grade C
- •Occult breast cancer is found pathologically no IDC lesion or only DCIS without micro-invasive lesion in the ipsilateral breast
- •patients with Her-2 overexpression had used, or is using, or intending to use adjuvant trastuzumab
- •severe heart dysfunction, heart functional classification is above Class III Table 2 Child-Pugh score of hepatic cirrhosis
Arms & Interventions
Switch to Zoladex + AI for 3-2 years
Patients who took tamoxifen or Fareston for 2-3 years were randomized into 2 groups (335 patients for each group). One group would switch to receive Zoladex 3.6mg depot subcutaneously every month and Aromidex 1mg/d po for another 3-2 years
Intervention: Zoladex+AI
TAM
Patients who took tamoxifen or Fareston for 2-3 years were randomized into 2 groups (335 patients for each group). One group would receive TAM 20mg/d treated for 3-2 years.
Intervention: TAM
Outcomes
Primary Outcomes
DFS
Time Frame: 5 Years
Disease free survival (DFS): DFS related events ware defined as local recurrence, distant metastasis, secondary primary cancer or death, whichever occurred first.during follow up
Secondary Outcomes
- OS(5 years)
- Time to distant metastasis(5 years)
- Osteoporosis related events(5 years)
- Other adverse events(5 years)
- Bilateral secondary primary breast cancer morbidity(5 years)
- DDFS(5 years)