Please select the eligibility criteria that correspond to the clinical trial below.
Title: Cyclophosphamide And Doxorubicin (CA) (4 VS 6 Cycles) Versus Paclitaxel (4 VS 6 Cycles) As Adjuvant Therapy For Breast Cancer in Women With 0-3 Positive Axillary Lymph Nodes:A 2X2 Factorial Phase III Randomized Study
Brief Summary: This randomized phase III trial studies cyclophosphamide and doxorubicin hydrochloride compared with paclitaxel as adjuvant therapy in treating breast cancer in women with 0-3 positive axillary lymph nodes. Giving additional cancer treatment after surgery may help to lower the risk that the cancer will come back (adjuvant therapy). Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin hydrochloride, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether the standard adjuvant therapy of cyclophosphamide and doxorubicin hydrochloride is more effective than paclitaxel in treating women with breast cancer


Options:
A: Inclusion Criteria:

* Histologically confirmed invasive unilateral breast cancer
* Age \> 65 and \< 80 years
* Intermediate-high risk of recurrence according to St. Gallen criteria: ER negative and PgR negative, or axillary lymph node metastasis, or tumor size \> 2 cm, or tumor grade 2 or 3 (intermediate or high)

Exclusion Criteria:

* Performance status \>1
* Distant metastasis
* Concomitant malignancy or malignancy within previous 5 years (except basal cell or spinocellular skin cancer and in situ cervical cancer if they have been adequately treated
* Previous breast cancer treatment
* Neutrophils \< 2000/mm3 or platelets \< 100000/mm3 or haemoglobin \< 10 g/dl
* Creatinine \> 1.25 the upper normal limit
* GOT and-or GPT and/or bilirubin \> 1.25 the upper normal limit
* Concomitant conditions that contraindicate the use of the drugs in the protocol
* Incapacity or refusal to provide informed consent
B: Inclusion Criteria:

* Histological proven primary breast cancer
* Tumour size \>0.5 cm and \<5 cm (pT1b-pT2, pN0, M0)
* Axillary lymph nodes tumour free (node-negative disease)
* Adequate surgical procedure: R0-resection and axillary dissection with more than 10 lymph nodes examined or adequate sentinel procedure in a qualified centre
* Frozen tumour tissue available (for analysis of biological markers and microarrays, centres with biological risk assessment only). The material has to be stored in liquid nitrogen immediately after excision.
* Paraffin blocks or (at least) pathology slides of primary tumour (stained and unstained) and axillary nodes (stained) available for central review.
* HER-2/neu determination by immunohistochemistry. Patients will be stratified to be HER-2/neu-negative or HER-2/neu-positive (HER-2/neu Score 3+, or HER-2/neu Score 2+ and FISH positive).
* No distant metastasis
* Age \>18 years, \<70 years
* Performance status ECOG \<2 (WHO Performance Status 0-1)
* Adequate cardiac function (echocardiographically measured left ventricular ejection fraction (LVEF) or shortening fraction (SF) within the normal limits, i.e. ≥55%)
* Adequate bone function (neutrophil count \>1.5 x109 /l and platelet count \>100 x109 /l)
* Adequate renal function (serum creatinine \<120 µmol/l or 1.35 mg/dl) and hepatic function (serum bilirubin \<1 x UNL, ASAT or ALAT (SGOT or SGPT) \<2,5 x UNL)
* Before patient registration/randomization, written informed consent must be obtained according to ICH/EU GCP, and national/local regulations

Exclusion Criteria:

* Chemotherapy contraindicated
* Inflammatory breast cancer, tumour infiltrated axillary lymph nodes including the sentinel node.
* Other concomitant pathology compromising survival (at entry), or preventing the administration of chemotherapy with either FEC or Docetaxel
* Other serious illness or medical condition that may interfere with the understanding and giving of informed consent and the conduct of the study
* Estimated life-expectancy \<10 years (irrespective of breast cancer diagnosis)
* Patient not accessible for treatment and follow up
* Endocrine treatment not according to the latest standard recommendations of the AGO Kommission "Mamma"
* Pregnancy, lactation (sufficient non-hormonal contraception in fertile women required)
* Surgery more than six weeks ago at the start of chemotherapy
* Pre-existing polyneuropathy
* Previous or concomitant other malignancy (including contralateral breast cancer) except adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix
* Prior chemotherapy or radiotherapy or endocrine therapy
C: Inclusion Criteria:

* Written informed consent
* Operable breast cancer patients (T1-T3) with negative axillary lymph nodes (10 axillary nodes dissection) and high risk criteria according to St. Gallen consensus criteria.
* Histologically proven breast cancer. Interval between surgery and registration is less than 60 days.
* Definitive surgical treatment must be either mastectomy, or breast conservative surgery. Margins of resected specimen from surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma in-situ is not considered as positive margin.
* Patients without proven metastatic disease.
* Estrogen and progesterone receptors performed on the primary tumour prior to randomization.
* Age between 18 years and 70 years.
* Karnofsky performance status index \> 80 %.
* Adequate hepatic, renal and heart functions.
* Adequate hematology levels.
* Negative pregnancy test

Exclusion Criteria:

* Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
* Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy.
* Prior radiation therapy for breast cancer.
* Bilateral invasive breast cancer.
* Pregnant, or lactating patients.
* Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment .
* Any T4 or N1-3 or M1 breast cancer.
* Pre-existing motor or sensory neurotoxicity of a severity grade 2 by NCI criteria.
* Other serious illness or medical condition
* Past or current history of neoplasm other than breast carcinoma.
* Ipsilateral ductal carcinoma in-situ (DCIS) of the breast.
* Lobular carcinoma in-situ (LCIS) of the breast.
* Chronic treatment with corticosteroids unless initiated \> 6 months prior to study entry and at low dose
* Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment should be stopped before study entry.
* Definite contraindications for the use of corticosteroids.
* Concurrent treatment with other experimental drugs.
* Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
* Concurrent treatment with any other anti-cancer therapy.
* Male patients.
D: Eligibility Criteria:

* Patients must have histologically confirmed invasive carcinoma of the female breast, with 0-3 positive axillary lymph nodes
* Patients must have 0-3 positive axillary lymph nodes to be eligible for this study; patients with node-negative breast cancer should have sufficiently "high risk" disease to warrant chemotherapy; as general guidelines, node-negative patients with tumors of \>= 1 cm or estrogen or progesterone receptor negative tumors of any size may be eligible; ultimately though, the definition of "high risk" may be determined by the treating physician, and if the treating physician feels the patient warrants chemotherapy, the patient is eligible; for patients with 1-3 positive axillary nodes, the patient is eligible regardless of primary breast tumor characteristics, if in the opinion of the treating physician, chemotherapy is deemed potentially beneficial to the patient
* If the patient has had a negative sentinel node biopsy, then no further axillary dissection is required, and the patient is determined to be node-negative; if an axillary dissection, without a sentinel node biopsy, is performed to determine nodal status, at least six axillary lymph nodes must be removed and analyzed and negative for the patient to be considered node-negative; axillary nodes with single cells or tumor clusters =\< 0.2 mm by either hematoxylin and eosin stain (H\&E) or immunohistochemistry (IHC), will be considered node-negative; lymph nodes positive for polymerase chain reaction (PCR) with tumor cells/clusters =\< 0.2 mm will be considered node-negative; any axillary lymph node with tumor clusters \> 0.2 mm will be considered positive
* If the patient has a sentinel node biopsy and one of the sentinel nodes is positive, as defined by tumor clusters \> 0.2 mm, an axillary dissection must be performed; a total of at least 6 axillary lymph nodes, including sentinel nodes plus the subsequent dissection, must be removed for the patient to be eligible; of all the lymph nodes removed from both the sentinel node procedure and the axillary dissection, 1-3 must be positive for the patient to be eligible as a node-positive patient; if an axillary dissection is done without a sentinel node procedure, at least 6 lymph nodes must be removed and a 1-3 nodes must be positive for the patient to be considered node-positive and eligible for this study
* Determination of involvement of axillary nodes with metastatic cancer will follow the revised tumor-node-metastasis (TNM) staging system: axillary nodes with single cells with tumor clusters =\< 0.2 mm, by either H\&E or immunohistochemistry (IHC), will be considered negative axillary node; lymph nodes positive for PCR with tumor cells/clusters \< 0.2 mm will be considered negative axillary node; any axillary lymph node with clusters \> 0.2 mm will be considered to be positive
* Patients with estrogen-receptor and/or progesterone receptor negative, positive, or unknown tumors are eligible; estrogen-receptor (ER) and progesterone receptor (PgR) assays should be performed by immunohistochemical methods according to the local institution's standard protocol
* Patients with human epidermal growth factor receptor 2 (HER2) positive, negative or unknown disease are eligible for this trial; patients whose tumors are HER2 positive by either immunohistochemistry 3+ staining or demonstrate gene amplification by fluorescence in situ hybridization (FISH) may receive trastuzumab
* There must be negative tumor margins for invasive cancer and ductal carcinoma in situ (DCIS) in the case of mastectomy or lumpectomy; lobular carcinoma in situ (LCIS) is acceptable at the margin
* Patients with multi-centric breast cancer are eligible as long as all known disease is resected with negative margins, and have 0-3 positive axillary lymph nodes
* Patients must be registered within 84 days of the last breast surgery; patients must have undergone either modified radical mastectomy or lumpectomy; for patients undergoing sentinel node sampling or axillary dissection a simple mastectomy is acceptable; lumpectomy patients must receive radiation therapy; for patients treated with radiation therapy prior to chemotherapy, the patients should be registered on this study after the conclusion of radiation, with chemotherapy administration beginning within 7 days of registration

  \* All primary breast and axillary node surgery must be completed prior to enrollment on study
* No previous trastuzumab, chemotherapy or hormonal therapy for this malignancy, except for tamoxifen therapy
* No previous anthracycline chemotherapy for any disease
* Patients with locally advanced breast cancer, inflammatory breast cancer or metastatic breast cancer are not eligible; patients with involvement of dermal lymphatics on pathology are not eligible, even if there are no clinical signs of inflammatory cancer
* Patients with bilateral, synchronous invasive breast cancer are eligible as long as both primary tumors; if a patient has an invasive cancer on one side that meets the eligibility criteria, and DCIS or LCIS on the contralateral side, the patient is eligible; DCIS or LCIS should be managed according to institutional guidelines
* Patients must be disease free from prior malignancies for \> 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma-in-situ of the cervix; patients with a history of invasive breast cancer, or DCIS are eligible if they have been disease free for \> 5 years; patients with a history of LCIS are eligible regardless of the interval from diagnosis
* Common Toxicity Criteria (CTC) performance status 0-1
* Women must not be pregnant or nursing
* Concomitant exogenous hormone therapy, including oral contraceptives, post-menopausal hormone replacement therapy, and raloxifene must be stopped before patients can be enrolled
* Patients may have received up to 4 weeks of tamoxifen therapy for this malignancy and still be eligible for this study; patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or for other indicators (e.g. osteoporosis) are eligible; tamoxifen therapy or other SERMs must be discontinued before the patient is enrolled on this study

  \* The use of bisphosphonates for the treatment of osteoporosis is permitted; the use of raloxifene is not permitted are enrollment on this study
* Patients must have adequate organ function including no active congestive heart failure, and no myocardial infarction \< 6 months from time of registration
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* Platelet count \>= 100,00/mm\^3
* Creatinine =\< 2.0 mg/dl
* Bilirubin =\< 1.5 x upper limits of institutional normal
* Patients may be enrolled on adjuvant bisphosphonate studies; patients may be enrolled concurrently or sequentially on 40101 and bisphosphonate trials
* Patients may be enrolled on adjuvant hormonal studies approved by CALGB or Cancer Trials Support Unit (CTSU), such as the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT) trials

Answer: D