Please select the eligibility criteria that correspond to the clinical trial below.
Title: Phase III Study of Doxorubicin/Cyclophosphamide (AC) Followed by Ixabepilone vs. AC Followed by Paclitaxel in Patients With Triple-Negative Early-Stage Breast Cancer
Brief Summary: This is a randomized, Phase III, open-label, multicenter study.


Options:
A: 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
B: DISEASE CHARACTERISTICS:

* Histologically confirmed operable stage IIA, IIB, or IIIA adenocarcinoma of the breast with histologically involved lymph nodes (T1, 2, or 3; N1 or 2; M0) OR high-risk node-negative disease (T2 or 3; N0)

  * Primary tumor at least 2.1 cm in diameter for node-negative disease
  * Bilateral breast disease allowed if at least 1 primary tumor meets the criteria above
* Must have had at least 6 axillary lymph nodes removed at dissection and at least one node positive for metastasis OR
* Sentinel node biopsy negative for metastasis (sentinel node biopsy positive allowed if enrolled on American College of Surgery Trial Z0011 and have beenrandomized to receive no axillary dissection)

  * Additional axillary nodes may be obtained provided they are also negative for metastasis
* Complete tumor removal by either a modified radical mastectomy or local excision plus axillary lymph node dissection (i.e., breast conservation therapy) or sentinel node biopsy

  * Tumor-free margins at least 1 mm for both invasive and noninvasive carcinoma except for lobular carcinoma in situ (less than 1 mm allowed)
* Concurrent enrollment on American College of Surgery Trial Z0010, Z0011, or NSABP B-32 allowed
* Hormone receptor status:

  * Estrogen receptor status positive, negative, or unknown

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Sex:

* Female

Menopausal status:

* Not specified

Performance status:

* Not specified

Life expectancy:

* Not specified

Hematopoietic:

* Neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* SGOT no greater than 2 times upper limit of normal

Renal:

* Creatinine no greater than 1.5 mg/dL

Cardiovascular:

* No history of myocardial infarction
* No congestive heart failure
* No significant ischemic or valvular heart disease

Other:

* No other prior invasive malignancies within the past 5 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
* No hypersensitivity to paclitaxel or docetaxel or other similarly formulated drugs (with Cremophor or polysorbate)
* Not pregnant or nursing
* Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy for breast cancer

Endocrine therapy:

* Prior tamoxifen of no more than 4 weeks duration for breast cancer allowed
* Prior tamoxifen or other selective estrogen receptor modulator (SERM) for chemoprevention (e.g., Breast Cancer Prevention Trial) or for other indications (e.g., osteoporosis) allowed
* No concurrent tamoxifen or other SERMs

Radiotherapy:

* No prior radiotherapy for this malignancy
* At least 2 weeks since prior radiotherapy to the breast for ductal carcinoma in situ

Surgery:

* See Disease Characteristics
* Less than 84 days since prior surgical procedure to adequately treat primary tumor
C: 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
D: Inclusion Criteria:

1. Female patients greater than or equal to18 years of age.
2. Histologically confirmed invasive unilateral breast cancer (regardless of

   histology).
3. Early-stage breast cancer, defined as:

   * Node-positive disease: \>0.2-mm metastasis in at least one lymph node (pN1mipN2b)OR
   * Node-negative, with primary tumor \>1.0 cm (T1c-T3).
4. Definitive loco-regional surgery must have been completed as specified

   below:
   * Patients must have undergone either breast conservation surgery

     (i.e., lumpectomy) or total mastectomy.
   * Surgical margins of the resected section must be histologically free of

   invasive adenocarcinoma and ductal carcinoma in situ.
   * Surgical margins involved with lobular carcinoma in situ (LCIS) will not

   be considered as a positive margin; therefore, such patients will be eligible for this study without additional resection.
   * Patients must have completed axillary lymph node sampling for the pathologic evaluation of axillary lymph nodes as specified below:

   Sentinel node biopsy and/or either lymph node sampling procedure or axillary dissection.
5. Multicentric and multifocal invasive breast cancer is eligible if loco-regional surgery has been completed as described above.
6. Patients with synchronous bilateral cancers are eligible only if:

   * All cancers are of triple-negative phenotype, defined as ER-, PR-, HER2-.
   * Eligibility based on the highest stage grouping.
7. HER2 negative tumors. HER2 negativity must be confirmed by one of the

   following:
   * FISH-negative (FISH ratio \<2.2), or
   * IHC 0-1+, or
   * IHC 2-3+ AND FISH-negative (FISH ratio \<2.2).
8. Estrogen receptor negative (\<10% staining by IHC for estrogen receptor).
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
10. Patient must be \<= 84 days from having completed definitive primary breast surgery (either lumpectomy or mastectomy).
11. MammoSite brachytherapy radiation is acceptable if it is performed

    immediately following surgery and prior to chemotherapy. It is recommended that chemotherapy be started no earlier than 2 weeks following the removal of the MammoSite balloon catheter.
12. Adequate hematologic function, defined by:

    * Absolute neutrophil count (ANC) \>1500/mm3
    * Platelet count \>=100,000/mm3
    * Hemoglobin \>9 g/dL
13. Adequate liver function, defined by:

    * AST and ALT \<=2.5 x the upper limit of normal (ULN)
    * Total bilirubin \<=1.5 x ULN (unless the patient has grade 1 bilirubin

    elevation due to Gilbert's disease or a similar syndrome involving slow

    conjugation of bilirubin).
14. Adequate renal function, defined by:

    * Serum creatinine \<=1.5 x ULN
15. Complete staging work-up \<=12 weeks prior to initiation of study treatment

    with computed tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred; abdomen accepted), and either a positron emission tomography (PET) scan or a bone scan.
16. Adequate cardiac function, defined by a left ventricular ejection fraction

    (LVEF) value of \>50% (or normal per institutional guidelines) by MUGA scan or echocardiogram (ECHO).
17. Adequate recovery from recent surgery. At least 1 week must have elapsed from the time of a minor surgery (i.e., sentinel node biopsy, port-acath (placement); at least 3 weeks must have elapsed from the time of a major surgery (i.e., lumpectomy, partial or total mastectomy, axillary lymph node dissection, breast reconstruction procedure).
18. Patients with previous history of invasive cancers (including breast cancer)

    are eligible if definitive treatment was completed more than 5 years prior to

    initiating current study treatment, and there is no evidence of recurrent disease.
19. Women of childbearing potential must have a negative serum or urine pregnancy test performed within 7 days prior to start of treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
20. Patient must be accessible for treatment and follow-up.
21. Women of childbearing potential must agree to use an acceptable method of birth control to avoid pregnancy for the duration of study treatment, and for 3 months thereafter.
22. All patients must be able to understand the investigational nature of the

study and give written informed consent prior to study entry.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.
2. History of previous diagnosis of invasive breast cancer (unless treated \>5 years previously with no recurrence). History of previously treated ductal carcinoma in situ (DCIS) is acceptable.
3. Any evidence or suspicion of metastatic disease other than ipsilateral

   axillary lymph nodes.
4. Any tumor \>=T4 (cutaneous invasion, deep adherence, inflammatory breast cancer).
5. Previous anthracycline chemotherapy.
6. Concurrent use of CYP3A4 inhibitors from 72 hours prior to initiation of

   study treatment until the end of treatment with ixabepilone.
7. Previous treatment for this breast cancer (including neoadjuvant

   chemotherapy).
8. Previous cancer (with the exception of non-melanoma skin cancer or cervical carcinoma in situ) in the past 5 years (including invasive contralateral breast cancer).
9. Peripheral neuropathy of \> grade 1 per NCI CTCAE v3.0.
10. Cardiac disease, including: congestive heart failure (CHF) \> Class II per

    New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, cardiac arrhythmia, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
11. History of hypersensitivity to CremophorEL (polyoxyethylated castor oil) or

    a drug formulated in CremophorEL such as paclitaxel.
12. Use of any investigational agent within 30 days of administration of the first dose of study drug.
13. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
14. Concurrent severe, uncontrolled infection or intercurrent illness including,

    but not limited to, ongoing or active infection, or psychiatric illness/social

    situations that would limit compliance with study requirements.
15. Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
16. Inability to comply with study and/or follow-up procedures.

Answer: D