Adjuvant AI Combined With Zoladex
Adjuvant AI Combined With Zoladex
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.
Inclusion Criteria:

 1. All patients must have signed and dated an informed consent form

 2. Patients must be female

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

 4. 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

 5. 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

 6. adjuvant endocrine therapy of TAM or Fareston must be started within 6 weeks when
 adjuvant chemotherapy or radiotherapy was finished

 7. 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

 8. Patients taking neo-chemotherapy are eligible, and lymph node status could be
 identified during surgery before neo-adjuvant chemotherapy or after neo-adjuvant
 chemotherapy. The definition of lymph node positive is:

 -  evaluation of lymph node status before neo-adjuvant chemotherapy must include
 pathological axillary nodes, internal mammary nodes (pN2b option) or
 supraclavicular nodes (pN3c option) involved. Micro-metastasis (i.e.≥0.2mm,
 pN1-pN3c) can be identified by the following method: fine needle aspiration (FNA)
 or sentinel node biopsy (SNB) or sampling/ total procedure of axillary dissection

 -  patients with no nodes positive after neo-adjuvant chemotherapy, lymph node
 positive must be evaluated during surgery. Its definition was the either of
 following:

 -  According the clinical practice guidelines of the local cancer center, it is
 acceptable when positive nodes was identified by SNB or axillary dissection

 -  There is pathological evidence in lymph nodes positive (pN1-pN3c) during
 breast surgery after neo-adjuvant chemotherapy

 9. Patients diagnosed as occult breast cancer clinically are found to pathologically have
 primary invasive carcinoma or DCIS with micro-invasive lesion in ipsilateral breast,
 and primary lesion or axillary node metastasis express ER and/or PR positive

 10. 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

 11. 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

 12. According to the standard operation principles for clinical practice of local cancer
 center, patients must be randomized within 4 weeks after definitive physical
 examination, imaging examination and laboratory testing show no evidence of recurrence
 or metastasis

 13. 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).

 14. 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)

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

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

 17. serum creatinine must be <2 times the ULN

 18. patients can swallow pills

 19. 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. history of AI therapy

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

 8. Occult breast cancer is found pathologically no IDC lesion or only DCIS without
 micro-invasive lesion in the ipsilateral breast

 9. patients with Her-2 overexpression had used, or is using, or intending to use adjuvant
 trastuzumab

 10. severe heart dysfunction, heart functional classification is above Class III Table 2
 Child-Pugh score of hepatic cirrhosis