Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III,Randomized,Open Label Study Comparing Simultaneous Versus Sequential Use of Adjuvant Chemotherapy and GnRHa up to 2-3 Years for ≤ 45 Year Old Pre-menopausal Hormone Receptor-positive Breast Cancer
Brief Summary: 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.


Options:
A: DISEASE CHARACTERISTICS:

* Histologically confirmed invasive breast cancer

  * Stage I-IIIA
  * Operable disease
* Bilateral synchronous invasive breast cancer allowed provided primary tumors were diagnosed no more than 1 month apart and both tumors are hormone receptor negative
* Must be planning to receive 3-8 months of a preoperative or postoperative chemotherapy regimen containing alkylating agents (anthracyclines or non-anthracyclines), meeting 1 of the following criteria:

  * 3-month/4-course anthracycline-based regimen
  * 6- to 8-month/course anthracycline-based regimen
  * 6- to 8-month/course non-anthracycline-based regimen
* Hormone receptor status:

  * Estrogen receptor negative
  * Progesterone receptor negative

PATIENT CHARACTERISTICS:

Age

* 18 to 49

Sex

* Female

Menopausal status

* Premenopausal

Performance status

* Zubrod 0-2

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

Other

* Not pregnant or nursing
* Fertile patients must use effective barrier contraception
* No other prior malignancy except adequately treated basal cell or squamous cell skin cancer or any in situ cancer from which the patient has been disease-free for at least 5 years after treatment with curative intent

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* See Disease Characteristics
* No prior cytotoxic chemotherapy

Endocrine therapy

* No other concurrent hormonal therapy

Radiotherapy

* Concurrent radiotherapy to the breast, chest wall, or lymph nodes allowed

Surgery

* See Disease Characteristics

Other

* Concurrent participation in other therapeutic clinical trials, including SWOG-S0221, allowed
B: DISEASE CHARACTERISTICS:

* Histologically confirmed breast cancer
* Completely resected disease

  * No clinically detectable residual loco-regional axillary disease
  * Prior surgery for primary breast cancer of 1 of the following types:

    * Total mastectomy with or without adjuvant radiotherapy
    * Breast-conserving procedure (e.g., lumpectomy, quadrantectomy, or partial mastectomy with margins negative\* for invasive disease and ductal carcinoma in situ) with planned radiotherapy NOTE: \*If all other margins are clear a positive posterior (deep) margin is permitted, provided the excision was performed down to the pectoral fascia and all tumor has been removed OR a positive anterior (superficial; abutting skin) margin is allowed provided all tumor was removed
* Tumor confined to the breast and axillary nodes

  * Tumor detected in internal mammary chain nodes by sentinel node procedure and is not enlarged is allowed
* Axillary lymph node dissection or a negative axillary sentinel node biopsy required

  * Patients with negative or microscopically positive axillary sentinel nodes are eligible
  * Positive sentinel nodes must have either axillary dissection or radiation of axillary nodes
* No distant metastases
* No locally advanced inoperable breast cancer, including any of the following:

  * Inflammatory breast cancer
  * Supraclavicular node involvement
  * Enlarged internal mammary nodes (unless pathologically negative)
* Bilateral synchronous invasive breast cancer allowed if disease meets all other eligibility criteria
* No prior ipsilateral or contralateral invasive breast cancer
* Hormone receptor status:

  * Estrogen and/or progesterone receptor positive

    * At least 10% of the tumor cells positive by immunohistochemistry
    * If \> 1 breast tumor, each tumor must be hormone receptor positive

PATIENT CHARACTERISTICS:

Age

* Premenopausal

Sex

* Female

Menopausal status

* Premenopausal

  * Estradiol in the premenopausal range after prior surgery OR meets the following criteria:

    * Menstruating regularly for the past 6 months
    * Has not used any form of hormonal treatment (including hormonal contraception) within the past 6 months

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* No systemic hepatic disease that would preclude prolonged follow-up

Renal

* No systemic renal disease that would preclude prolonged follow-up

Cardiovascular

* No systemic cardiovascular disease that would preclude prolonged follow-up
* No prior thrombosis (e.g., deep vein thrombosis) and/or embolism unless patient is medically suitable

Pulmonary

* No systemic pulmonary disease that would preclude prolonged follow-up

Other

* Not pregnant or nursing
* Fertile patients must use effective nonhormonal contraception
* No history of noncompliance to medical regimens
* No other nonmalignant systemic disease that would preclude prolonged follow-up
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, nonbreast carcinoma in situ, contralateral or ipsilateral carcinoma in situ of the breast, or other nonrecurrent invasive nonbreast malignancy, including any of the following:

  * Stage I papillary thyroid cancer
  * Stage IA carcinoma of the cervix
  * Stage IA or B endometrioid endometrial cancer
  * Borderline or stage I ovarian cancer
* No psychiatric, addictive, or other disorder that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Prior or concurrent neoadjuvant or adjuvant trastuzumab allowed

Chemotherapy

* No prior neoadjuvant or adjuvant chemotherapy

Endocrine therapy

* No prior tamoxifen, other selective estrogen-receptor modulators (SERMs) (e.g., raloxifene), or hormone replacement therapy for more than 1 year before breast cancer diagnosis
* No prior neoadjuvant or adjuvant endocrine therapy since diagnosis of breast cancer
* No concurrent oral or transdermal hormonal therapy
* No other concurrent estrogen, progesterone, or androgens
* No other concurrent aromatase inhibitors
* No concurrent oral or other hormonal contraceptives (i.e., implants or depot injections)

Radiotherapy

* See Disease Characteristics
* No prior ovarian radiotherapy

Surgery

* See Disease Characteristics
* No prior bilateral oophorectomy

Other

* No concurrent bisphosphonates, except in the following cases:

  * Bone density is at least 1.5 standard deviations below the young adult normal mean
  * Participation in a randomized clinical study testing bisphosphonates in the adjuvant breast cancer setting
* No other concurrent investigational agents
C: 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
D: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed breast cancer resected at time of original diagnosis

  * Stage I-III disease
* Candidate for 1 of the following adjuvant chemotherapy regimens:

  * FEC (fluorouracil, epirubicin hydrochloride, and cyclophosphamide) every 21 or 28 days
  * CMF (cyclophosphamide, methotrexate, and fluorouracil) every 28 days
  * A→CMF (doxorubicin hydrochloride followed by CMF)
  * EC→P (epirubicin hydrochloride and cyclophosphamide every 21 days followed by paclitaxel every 21 days)
  * FEC→P (FEC every 21 days followed by paclitaxel every 21 days)
  * EC→D (EC every 21 days followed by docetaxel every 21 days)
  * AC (doxorubicin hydrochloride and cyclophosphamide) every 21 days
  * AC→P (AC every 21 days followed by paclitaxel every 21 days)
  * E→CMF (epirubicin hydrochloride followed by CMF every 28 days)
* No evidence of metastases or localized or distant recurrence

  * Investigation to exclude metastases required for any suspicious manifestation
* Premenopausal, defined as the presence of active menstrual cycles or normal menses within six weeks before initiation of chemotherapy
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* Female
* No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or adequately treated in situ carcinoma of the cervix
* No history of noncompliance to medical regimens or patients who are considered potentially unreliable
* Not pregnant or nursing
* Negative pregnancy test

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior chemotherapy and/or radiotherapy for cancer or non-neoplastic disease
* No other concurrent hormonal therapy except for tamoxifen

Answer: C