Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Phase II Trial of Combination Anastrozole (NSC #719344) Plus ZD1839 (Iressa, NSC #715055, IND #61187) and of Combination Fulvestrant (NSC #719276) Plus ZD1839 in the Treatment of Postmenopausal Women With Hormone Receptor-Positive Metastatic Breast Cancer
Brief Summary: This randomized phase II trial is studying how well giving gefitinib together with anastrozole works compared to giving gefitinib together with fulvestrant in treating postmenopausal women with recurrent or metastatic breast cancer. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using anastrozole and fulvestrant may fight breast cancer by blocking the use of estrogen. Gefitinib (ZD1839) may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It is not yet known whether gefitinib is more effective when combined with anastrozole or fulvestrant in treating breast cancer.


Options:
A: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the breast.
* Metastatic disease must be measurable or evaluable
* Relapsed or progressed during prior treatment with single-agent NSAI, meeting either of the following criteria:
* NSAI given as adjuvant therapy that lasted ≥ 12 months OR
* Achieved an objective CR, PR, or SD that that lasted ≥ 6 months after prior 1st-line
* Female postmenopausal patients

Exclusion Criteria:

* Hormone receptor status1. ER -ve and PgR NK2. ER-ve and PgR -ve3. ER NK
* Prescribed Tamoxifen for metastatic disease
* Rapidly progressive visceral disease
* Patients with malignancies within the last 5 years.
B: Inclusion Criteria:

* Patients must have estrogen and/or progesterone receptor positive histologically confirmed adenocarcinoma of the breast with measurable recurrent or metastatic carcinoma of the breast
* Baseline measurements and evaluations of involved sites should be performed as close as possible to study entry, but must be within 4 weeks prior to randomization
* Patients with available tissue blocks from either the primary or metastatic site must submit the tissue for EGFR analysis
* All patients must be postmenopausal females defined by:

  * Prior bilateral oophorectomy or bilateral ovarian irradiation
  * No menstrual period for 12 months or longer. If age 55 years or less and on tamoxifen within the prior 6 months, must have an estradiol level in the postmenopausal range
* Patients must not have had more than 2 prior chemotherapy regimens for metastatic disease and no chemotherapy within 3 weeks prior to randomization; no concurrent chemotherapy is allowed while on protocol therapy
* Patients must not have prior hormonal therapy for metastatic disease; no prior therapy in the adjuvant setting with an estrogen receptor down-regulator (e.g. fulvestrant) or an aromatase inhibitor (e.g. anastrozole, letrozole, exemestane, aminoglutethamide); non-protocol concurrent hormonal therapy is not allowed
* Patients must not have had prior therapy with agents that target EGFR
* Previous, but not concomitant, therapy with trastuzumab (Herceptin) is allowed; patients must not receive trastuzumab (Herceptin) within 3 weeks prior to randomization
* Patients must have ECOG performance status of 0, 1, or 2
* Neutrophils \>= 1500/mm\^3
* Platelets \>= 100,000/mm\^3
* Bilirubin =\< 1.25 x upper limit of normal
* SGPT (ALT) and SGOT (AST) =\< 2.5 x upper limit of normal if no demonstrable liver metastases or =\< 5 times upper limit of normal in the presence of liver metastases
* Calculated creatinine clearance \>= 30ml/min
* INR, PT and PTT within normal range
* Patients must not be receiving therapy with anticoagulants or have other contraindication to i.m. injections
* Patients must not have a history of central nervous system metastasis
* Patients may receive concurrent radiation therapy to painful sites of boney disease or areas of impending fracture as long as the radiation therapy is initiated prior to study entry and sites of measurable disease outside the radiation therapy port are available to follow; patient who have received prior radiation therapy must have recovered from toxicity of the prior radiation therapy
* Patients must not take the following medications that may alter ZD1839 pharmacokinetics while enrolled in this trial: phenytoin, carbamazapine, phenobarbitol, rifampicin, and St. John's Wort, oxcarbazepine, rifapentine, modafinil, and griseofulvin
* Patients age =\< 55 years must not be receiving LHRH agonists or antagonists within 3 months prior to randomization
* Patients who have an ocular inflammation or infection should be fully treated before entry into the trial; patients with a neuropathic keratopathy or diabetes or those with anterior basement membrane disease must be advised of the need for frequent opthalmalogic exams
* Patients who continue to wear contact lenses must be advised that they have an increased risk of ocular events; the decision to wear contact lenses should be discussed with the patient's treating oncologist and ophthalmologist
* Patients must not suffer from medical or psychiatric conditions that would interfere with protocol compliance, the ability to provide informed consent, or assessment of response or anticipated toxicities
* Patients must be disease-free of prior invasive malignancies for \> 5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
C: DISEASE CHARACTERISTICS:

* Histologically confirmed breast cancer meeting 1 of the following criteria:

  * Metastatic disease (M1)
  * Multiple sites of new disease that is clinically obvious metastatic disease (e.g., multiple sites of new osseous disease)
* Measurable or nonmeasurable disease
* No known brain or CNS metastases
* Hormone receptor status:

  * Estrogen-receptor positive\* AND/OR
  * Progesterone-receptor positive\* NOTE: \*Positivity defined as estrogen binding of \> 10 fmol/mg cytosol protein by ligand binding assay or positive by immunohistochemistry

PATIENT CHARACTERISTICS:

Age

* Not specified

Sex

* Female

Menopausal status

* Postmenopausal, as defined by 1 of the following:

  * Prior bilateral oophorectomy
  * More than 12 months since last menstrual period with no prior hysterectomy
  * At least 55 years of age with prior hysterectomy
  * Under 55 years of age with a prior hysterectomy without oophorectomy and with estradiol and follicle-stimulating hormone levels consistent with menopause

Performance status

* Zubrod 0-2

Life expectancy

* Not specified

Hematopoietic

* No bleeding diathesis (e.g., disseminated intravascular coagulation or clotting factor deficiency)

Hepatic

* INR ≤ 1.6

Renal

* Not specified

Other

* HIV negative
* No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

* No prior immunotherapy for recurrent or metastatic disease

Chemotherapy

* No prior chemotherapy for recurrent or metastatic disease
* More than 12 months since prior adjuvant or neoadjuvant chemotherapy
* No concurrent chemotherapy for malignancy

Endocrine therapy

* Prior adjuvant hormonal therapy allowed
* At least 12 months since prior adjuvant luteinizing hormone-releasing hormone (LHRH) analogues

  * Menstrual periods must not have resumed since LHRH therapy
* More than 12 months since prior adjuvant or neoadjuvant aromatase inhibitors (e.g., anastrozole, letrozole, or exemestane)
* More than 12 months since prior fulvestrant
* No prior hormonal therapy for recurrent or metastatic disease
* No other concurrent hormonal therapy for malignancy
* No concurrent hormone replacement therapy

Radiotherapy

* Not specified

Surgery

* Not specified

Other

* No long-term anticoagulant therapy (except antiplatelet therapy)
D: Inclusion Criteria:

* Postmenopausal advanced breast cancer with oestrogen receptor positive
* Progression under first-line anti-oestrogen therapy.

Exclusion Criteria:

* Life-threatening metastasis; contraindication to anastrozole
* \>2 regimens of hormonotherapy for advanced breast cancer

Answer: B