Simultaneous Versus Sequential Use of Adjuvant Chemotherapy and GnRHa in Treating ER+,Premenopausal Breast Cancer
Simultaneous Versus Sequential Use of Adjuvant Chemotherapy and GnRHa in Treating ER+,Premenopausal Breast Cancer
The present study is a randomized open-label -phase III study that aims to compare the
 efficacy and safety of the adjuvant chemotherapy with simultaneous or sequential application
 of Zoladex up to 2-3 years for ≤ 45 year old premenopausal hormone receptor-positive breast
 cancer.
Data showed that ovarian suppression therapy may protect the ovarian function in
 premenopausal patients received chemotherapy for breast cancer. However this is still a
 controversial issue. Sequential use of GnRHa (Zoladex) as ovarian suppression treatment after
 chemotherapy has been established as an effective endocrine therapy for ER positive
 premenopausal breast cancer. The present study is a randomized open-label phase III study
 that aims to observe the efficacy and safety of the adjuvant chemotherapy with simultaneous
 combination of Zoladex up to 2-3years and chemotherapy compared with the sequential schedule
 in ≤ 45 year old premenopausal hormone receptor-positive breast cancer patients.
Inclusion Criteria:

 1. female

 2. Primary invasive breast cancer pathologically approved by core needle or open biopsy

 3. Patients must have undergone standard surgery for primary breast cancer as shown in
 the following:

 -  mastectomy

 -  breast conservation surgery followed by whole breast radiation

 -  axillary dissection or sentinel node biopsy

 4. Need adjuvant chemotherapy after surgery

 5. Patients taking neo-chemotherapy are eligible

 6. Patients with synchronous bilateral cancers are eligible on the condition that If one
 side is IDC and the other side is DCIS, the IDC side should be of the ER and/or PR
 positive phenotype and IF two sides are both IDC, they must be ER and/or PR positive
 phenotype at the same time

 7. Hormone receptor positive (≥＋) is defined as detecting ER or PR expression at any time
 is eligible. The situation of only PR positive and ER negative is eligible, too

 8. Based on the study objective, all patients are required to be premenopausal as defined
 by

 -  menstruating actively

 -  less than 6 months since last menstrual period (LMP), or patients younger than 40
 years of age who became amenorrheic not more than 1 year if the serum free E2、FSH
 and LH level was premenopausal (according to the reference value of local
 center).

 -  had previous hysterectomy with one or both ovaries left intact are eligible if
 the serum free E2、FSH and LH level are premenopausal (according to the reference
 value of local center).

 9. patients must have an ECOG performance status of 0 or 1 (0-fully active, able to carry
 on all pre-disease performance without restriction, 1-restricted in physical strenuous
 actively but ambulatory)

 10. leucocyte count must be ≥ 3.0*10^9/L and platelet count must be ≥ 100*10^9/L

 11. AST/SGOT or ALT/AGPT must be < 3 times the ULN

 12. serum creatinine must be < 2 times the ULN

 13. pregnancy testing is negative and are willing to do contraception during the treatment
 period

 Exclusion Criteria:

 1. patients with metastatic malignant tumor

 2. previous history of asynchronous bilateral breast cancer

 3. 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

 4. any non-malignant systemic disease which interfere long time follow up

 5. history of medical ovarian ablation therapy

 6. severe live dysfunction, Child-Pugh is grade C

 7. Severe renal dysfunction

 8. Occult breast cancer

 9. severe heart dysfunction, heart functional classification is above Class III