Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer
Brief Summary: This randomized phase II trial studies how well paclitaxel with or without carboplatin and/or bevacizumab followed by doxorubicin and cyclophosphamide works in treating patients with breast cancer that can be removed by surgery. Drugs used in chemotherapy, such as paclitaxel, carboplatin, doxorubicin, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bevacizumab may stop the growth of tumor cells by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.


Options:
A: Inclusion Criteria:

* Invasive breast cancer, diagnosed by core needle or incisional biopsy (excisional biopsy not permitted)
* The invasive tumor must be hormone receptor-poor, defined as both estrogen receptor (ER) and progesterone receptor (PgR) negative or staining present in =\< 10% of invasive cancer cells by immunohistochemistry (IHC)
* The invasive tumor must be HER2-negative, defined as IHC 0-1+ or with a fluorescent in situ hybridization (FISH) ratio (HER2 gene copy/chromosome 17) of \< 2.0 if IHC 2+
* Clinical stage II-III invasive breast cancer with intent to perform surgical resection after neoadjuvant therapy; patients with inflammatory breast cancer are not eligible; staging to rule out metastatic disease is recommended for clinical stage III patients
* Patients with multicentric or bilateral disease are eligible if the target lesion meets eligibility criteria
* Patient agrees to undergo pretreatment research biopsies
* No prior chemotherapy, hormone therapy, or radiation therapy with therapeutic intent for this cancer
* The target lesion in the breast must be \>= 1 cm, clinically or radiographically; palpable or radiographically measurable axillary adenopathy will be recorded but will not serve as measurable disease for the primary endpoint; patients with axillary disease only (no identifiable tumor in the breast that is \>= 1 cm on physical exam or radiographic study) are not eligible to participate
* Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower gastrointestinal \[GI\] bleeding) within 6 months of registration are not eligible
* No serious or non-healing wound, skin ulcers or bone fracture; no abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within the past 6 months; no major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during the course of study
* The following are not considered to be major surgical procedures that would be prohibited in the 28 days prior to, or following study randomization: obtaining the required research needle biopsies; placement of a radiopaque clip to localize a tumor or tumors for subsequent surgical resection; placement of a port for central venous access; fine needle aspiration of a prominent or suspicious axillary lymph node; needle biopsy of a clinically or radiographically detected lesion to rule out metastatic disease; or pretreatment sentinel lymph node sampling
* No baseline neuropathy grade \>= 2
* Zubrod performance status 0-1
* Pregnant or nursing women are not eligible; all women of reproductive potential must have a negative pregnancy test at baseline and agree to use an effective, non-hormonal method of contraception during the entire period of treatment on the study
* Patients with congestive heart failure are not eligible, nor are patients with myocardial infarction, unstable angina pectoris, an arterial thrombotic event, stroke or transient ischemia attack (TIA) within the past 12 months, uncontrolled hypertension (systolic blood pressure \[SBP\] \> 160 or diastolic blood pressure \[DBP\] \> 90), uncontrolled or symptomatic arrhythmia, or grade II or greater peripheral vascular disease
* Patients must have a pretreatment multi gated acquisition (MUGA) scan or echocardiogram with a left ventricular ejection fraction (LVEF) above the institutional lower limit of normal
* Granulocytes \> 1,000/mcl
* Platelets \> 100,000/mcl
* Total bilirubin =\< 1.5 x upper limits of normal
* Calculated or measured \> 30 ml/min
* Urine protein =\< 1+ or urine protein to creatinine (UPC) ratio \< 1

  * Patients discovered to have \>= 2+ proteinuria at baseline must undergo a 24-hour urine collection that must demonstrate \< 1 g of protein/24 hr, or UPC ratio \< 1 to allow participation in the study
* Serum alanine aminotransferase (ALT) =\< 2.5 x upper limits of normal
* Serum beta human chorionic gonadotropin (HCG) negative (for women of child bearing potential)
* Prothrombin time (PT)/international normalized ratio (INR) =\< 1.5 x upper limit of normal (ULN)

  * Unless patient is on therapeutic doses of warfarin; if so, the patient must have an INR =\< 3 on a stable dose of warfarin, must have not active bleeding or pathologic condition that is associated with a high risk of bleeding
B: Inclusion Criteria:

* Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly)
* Histologically confirmed unilateral primary invasive carcinoma of the breast
* Clinical T1 - T4 (except inflammatory breast cancer)
* All clinical N (cN)
* No clinical evidence for distant metastasis (M0)
* Known HR status and HER2 status (local pathology) Tumor block available for central pathology review
* Performance Status ECOG ≤ 1 or KI ≥ 80%
* Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients
* Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
* The patient must be accessible for treatment and follow-up

Additional Inclusion criteria for participation in the HR-/HER2+ sub-protocol:

* Confirmed ER and PR negative and HER2+ by central pathology
* Clinical cT1c - T4a-c (participation of patients with tumors \>cT2 is strongly recommended)
* All clinical N (participation of patients with cN0, if at least cT1c is strongly recommended)
* Patients must qualify for neoadjuvant treatment
* LVEF \> 50%; LVEF within normal limits of each institution measured by echocardiography and normal ECG (within 42 days prior to induction treatment)

Exclusion Criteria:

* Known hypersensitivity reaction to the compounds or incorporated substances
* Prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
* Non-operable breast cancer including inflammatory breast cancer
* Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
* Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
* Male breast cancer
* Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
* Breast feeding woman
* Sequential breast cancer
* Reasons indicating risk of poor compliance Patient not able to consent

Additional Exclusion Criteria for participation in the HER2+/HR- sub-protocol:

* Known polyneuropathy ≥ grade 2
* Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study
* Inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.)
* Uncompensated cardiac function (current unstable ventricular arrhythmia requiring treatment, history of symptomatic CHF NYHA classes II-IV), history of myocardial infarction or unstable angina pectoris within 6 months of enrollment, history of severe hypertension, CAD - coronary artery disease)
* Severe dyspnea
* Abnormal blood values:
* Thrombocytopenia \> CTCAE grade 1
* Increases in ALT/AST \> CTCAE grade 1
* Hypokalaemia \> CTCAE grade 1
* Neutropenia \> CTCAE grade 1
* Anaemia \> CTCAE grade 1
C: Inclusion Criteria(Screening):

* Female patients, age at diagnosis 18 - 75 years
* Histological confirmed unilateral primary invasive carcinoma of the breast
* Adequate surgical treatment with complete resection of the tumor (R0) and resection of \> or = 10 axillary nodes or SLN in clinically N0 patients
* T1 - T4 (if operable, inflammatory breast cancer is excluded)
* Her-2 non-over expressing tumor confirmed by IHC/FISH
* Estrogen and/or progesterone receptor analysis performed on the primary tumor prior to randomization. Results must be known at the time of randomization
* Node positive disease or node negative disease with at least one other risk factor (tumor size \> or = 2 cm, grade \> or = 2, ER and PR negative, high uPA//PAI-1 levels)
* No evidence for distant metastasis (M0) after conventional staging
* Performance Status ECOG \< or = 1 or KI \> or = 80 %
* The patient must be accessible for treatment and follow-up
* Written informed consent for central pathology review and evaluation of Recurrence Score (HR positive) and participation in the planB trial prior to beginning specific protocol procedures

HR positive patients:

* Patient willingness to participate in adjuvant chemotherapy planB trial if RS \> 11
* Indication for chemotherapy given provided either \> 4 involved lymph nodes or RS \> 11 in 1-3 lymph nodes or N0 disease

Additional Inclusion Criteria (Randomisation to chemotherapy):

* Laboratory requirements (within 21 days prior to randomization):

  * Leucocytes \> or = 3.5 109/L
  * platelets \> or = 100 109/L
  * haemoglobin \> or = 10 g/dL
  * total bilirubin \< or = 1 ULN
  * ASAT (SGOT) and ALAT (SGPT) \< or = 2.5 UNL
  * creatinine \< 175 ymol/L (2 mg/dL)
* Negative pregnancy test (urine or serum) within 7 days prior to randomization in premenopausal patients
* LVEF within normal limits of each institution measured by echocardiography or MUGA scan and

Exclusion Criteria(Screening):

* HER2 over expression confirmed by IHC/FISH/CISH
* Known hypersensitivity reaction to the compounds or incorporated substances
* Known polyneuropathy \> or = grade 2
* Severe and relevant comorbidity that would interact with the application of cytotoxic agents or the participation in the study including acute cystitis and ischuria and chronic kidney disease.
* Prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri or ipsilateral ductal carcinoma in-situ (DCISpTis of the breast)
* Non-operable breast cancer including inflammatory breast cancer
* Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
* Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry
* Male breast cancer
* Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less then 1% failure rate) non-hormonal contraceptive measures during the study treatment
* Breast feeding woman
* Sequential breast cancer
* Lack of patient compliance

Additional Exclusion Criteria (Randomisation):

* Inadequate organ function including:

  * Leucocytes \< 3,5 G/l
  * platelets \< 100 G/l
  * creatinine or bilirubin above normal limits
  * alkaline phosphatise \> 5 UNL
  * ASAT and/or ALAT associated with AP \> 2.5 UNL
  * uncompensated cardiac function
* Time since axillary dissection \> 42 days
D: Inclusion Criteria:

* Female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for ADAPT Elderly)
* Histologically confirmed unilateral primary invasive carcinoma of the breast
* Clinical T1 - T4 (except inflammatory breast cancer)
* All clinical N (cN)
* No clinical evidence for distant metastasis (M0)
* Known HR status and HER2 status (local pathology)
* Tumor block available for central pathology review
* Performance Status ECOG \<= 1 or KI \>= 80%
* Negative pregnancy test (urine or serum) within 7 days prior to start of induction treatment in premenopausal patients
* Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
* The patient must be accessible for treatment and follow-up

Exclusion Criteria:

* Known hypersensitivity reaction to the compounds or incorporated substances
* Prior malignancy with a disease-free survival of \< 10 years, except curatively treated basalioma of the skin or pTis of the cervix uteri
* Non-operable breast cancer including inflammatory breast cancer
* Previous or concurrent treatment with cytotoxic agents for any reason after consultation with the sponsor
* Concurrent treatment with other experimental drugs. Participation in another interventional clinical trial with or without any investigational not marketed drug within 30 days prior to study entry
* Male breast cancer
* Concurrent pregnancy; patients of childbearing potential must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment
* Breast feeding woman
* Sequential breast cancer
* Reasons indicating risk of poor compliance
* Patients not able to consent

Answer: A