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SCREENING PRIOR TO INITIATING CHEMOTHERAPY |
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Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 |
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The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle |
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biopsy |
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The primary breast tumor must be palpable and measure greater than or equal 2.0 cm on |
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physical exam |
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The regional lymph nodes can be cN0, cN1, or cN2a |
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Histological grade II or III tumor |
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Ipsilateral axillary lymph nodes must be evaluated by imaging (mammogram, ultrasound |
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and/or MRI) within 6 weeks prior to initiating chemotherapy. If suspicious or abnormal, FNA |
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or core biopsy is recommended, also within 6 weeks prior to initiating chemotherapy |
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Findings of these evaluations will be used to determine the nodal status prior to |
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initiating chemotherapy |
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Nodal status - negative: Imaging of the axilla is negative; Imaging is suspicious or |
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abnormal but the FNA or core biopsy of the questionable node(s) on imaging is |
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negative |
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Nodal status - positive: FNA or core biopsy of the node(s) is cytologically or |
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histologically suspicious or positive. Imaging is suspicious or abnormal but FNA or |
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core biopsy was not performed |
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Tumor specimen obtained at the time of diagnosis must have ER and progesterone receptor |
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(PgR) analysis assessed by current ASCO/CAP Guidelines. Patients are eligible with either |
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Immunohistochemistry (IHC) 0-1+; or |
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hormone receptor-positive or hormone receptor-negative tumors |
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Tumor specimen obtained at the time of diagnosis must have been determined to be |
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HER2-negative as follows |
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IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to |
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absolute neutrophil count (ANC) must be greater than or equal 1200/mm3 |
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chromosome enumeration probe 17 (CEP17) less than 2.0, and if reported, average HER2 |
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platelet count must be greater than or equal 100,000/mm3; and |
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gene copy number less than 4 signals/cells; or |
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hemoglobin must be greater than or equal 10 g/dL |
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ISH non-amplified with a ratio of HER2 to CEP17 less than 2.0, and if reported |
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average HER2 gene copy number less than 4 signals/cells |
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Blood counts performed within 6 weeks prior to initiating chemotherapy must meet the |
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following criteria |
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alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab; and |
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aspartate aminotransferase (AST) must be less than or equal to 1.5 x ULN for the lab |
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The following criteria for evidence of adequate hepatic function performed within 6 weeks |
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prior to initiating chemotherapy must be met |
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total bilirubin must be less than or equal to upper limit of normal (ULN) for the lab |
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unless the patient has a bilirubin elevation greater than ULN to 1.5 x ULN due to |
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Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and |
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Alkaline phosphatase and AST may not both be greater than the ULN. For example, if the |
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alkaline phosphatase is greater than the ULN but less than or equal to 2.5 x ULN, the |
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AST must be less than or equal to the ULN. If the AST is greater than the ULN but less |
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than or equal to 1.5 x ULN, the alkaline phosphatase must be less than or equal to |
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ULN. Note: If alanine aminotransferase (ALT) is performed instead of AST (per |
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institution's standard practice), the ALT value must be less than or equal to 1.5 x |
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ULN; if both were performed, the AST must be less than or equal to 1.5 x ULN |
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Patients with AST or alkaline phosphatase greater than ULN are eligible for inclusion in |
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the study if liver imaging (CT, MRI, PET-CT, or PET scan) performed within 6 weeks prior to |
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initiating chemotherapy does not demonstrate metastatic disease and the requirements in |
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next criteria are met |
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MAIN STUDY ENROLLMENT |
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Patients with alkaline phosphatase that is greater than ULN but less than or equal to 2.5 x |
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ULN or unexplained bone pain are eligible for inclusion in the study if a bone scan, PET-CT |
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scan, or positron emission tomography (PET) scan performed within 6 weeks prior to |
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initiating chemotherapy does not demonstrate metastatic disease |
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Serum creatinine performed within 6 weeks prior to initiating chemotherapy must be less |
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than or equal to 1.5 x ULN for the lab |
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The left ventricular ejection fraction (LVEF) assessment by echocardiogram or multi-gated |
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acquisition (MUGA) scan performed within 90 days prior to initiating chemotherapy must be |
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greater than or equal 55 percent regardless of the facility's lower limit of normal (LLN) |
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Patients with reproductive potential must agree to use an effective non-hormonal method of |
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contraception during therapy and for at least 7 months after the last dose of study |
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Tumor determined to have abnormal HER2-driven signaling activity based on the CELx HSF |
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test |
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______________ |
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T4 tumors including inflammatory breast cancer
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FNA alone to diagnose the breast cancer
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Excisional biopsy or lumpectomy performed prior to initiating chemotherapy
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Surgical axillary staging procedure prior to initiating chemotherapy. Pre-neoadjuvant
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therapy sentinel node biopsy is not permitted. (FNA or core biopsy is acceptable.)
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Definitive clinical or radiologic evidence of metastatic disease. Required imaging studies
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must have been performed within 6 weeks prior to initiating chemotherapy
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Synchronous bilateral invasive breast cancer. (Patients with synchronous and/or previous
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contralateral ductal carcinoma in situ [DCIS] or lobular carcinoma in situ [LCIS] are
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eligible.)
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Any previous history of ipsilateral invasive breast cancer or ipsilateral DCIS. (Patients
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with synchronous or previous ipsilateral LCIS are eligible.)
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Previous therapy with anthracycline, taxanes, trastuzumab, or other HER2 targeted therapies
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for any malignancy
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Any sex hormonal therapy, e.g., birth control pills, ovarian hormone replacement therapy
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etc. (These patients are eligible if this therapy is discontinued prior to initiating
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chemotherapy.)
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History of non-breast malignancies (except for in situ cancers treated only by local
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excision and basal cell and squamous cell carcinomas of the skin) within 2 years prior to
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initiating chemotherapy
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Cardiac disease (history of and/or active disease) that would preclude the use of the drugs
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Poorly controlled diabetes mellitus
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included in the treatment regimens. This includes but is not confined to
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Active cardiac disease: angina pectoris that requires the use of anti-anginal
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medication; ventricular arrhythmias except for benign premature ventricular
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Patients known to be HIV positive
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contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not
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controlled with medication; conduction abnormality requiring a pacemaker; valvular
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disease with documented compromise in cardiac function; and symptomatic pericarditis
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History of cardiac disease: myocardial infarction documented by elevated cardiac
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enzymes or persistent regional wall abnormalities on assessment of left ventricular
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(LV) function; history of documented congestive heart failure (CHF); and documented
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cardiomyopathy
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Uncontrolled hypertension defined as sustained systolic BP greater than 150 mmHg or
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Conditions that would prohibit administration of corticosteroids
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diastolic BP greater than 90 mmHg. (Patients with initial BP elevations are eligible prior
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to initiating chemotherapy if initiation or adjustment of BP medication lowers pressure.)
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Active hepatitis B or hepatitis C with abnormal liver function tests. Intrinsic lung
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disease resulting in dyspnea
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Active infection or chronic infection requiring chronic suppressive antibiotics
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Nervous system disorder (paresthesia, peripheral motor neuropathy, or peripheral sensory
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neuropathy) greater than or equal to grade 2, per the CTCAE v4.0
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Malabsorption syndrome, ulcerative colitis, resection of the stomach or small bowel, or
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other disease significantly affecting gastrointestinal function
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Other non-malignant systemic disease that would preclude treatment with any of the
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treatment regimens or would prevent required follow-up
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Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10
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mg/day methylprednisolone equivalent (excluding inhaled steroids)
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Known hypersensitivity to any of the study drugs or any of the ingredients or excipients of
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these drugs (e.g., Cremophor EL), including sensitivity to benzyl alcohol
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Pregnancy or lactation at the initiation of chemotherapy. (Note: Pregnancy testing must be
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performed within 2 weeks prior to initiating chemotherapy according to institutional
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standards for women of childbearing potential.)
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Psychiatric or addictive disorders or other conditions that, in the opinion of the
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investigator, would preclude the patient from meeting the study requirements
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