Use of PRO Onc Assay to Assess HER2 in Patients With Metastatic Breast Cancer

Inclusion Criteria

Part I

• Women with HER2-negative breast cancer, as defined by FISH testing. (FISH testing may have been performed on the primary tumor, or subsequently on a biopsy of a metastatic lesion.)
• Patients should be currently receiving chemotherapy, or scheduled to start chemotherapy (second-line or subsequent), for HER2-negative metastatic breast cancer.
• To begin protocol treatment, patients must have progressed after at least 1 previous chemotherapy regimen for metastatic breast cancer.
• Patients who are ER/PR positive or negative are eligible. ER/PR positive patients should be refractory to hormonal therapy, or not good candidates for hormonal therapy due to clinical features.
• ECOG performance status of 0, 1 or 2.
• Adequate recovery from recent surgery; ≥ 1 week must have elapsed from the time of a minor surgery; ≥ 4 weeks must have elapsed from the time of a major surgery.
• Patients must have measurable disease per RECIST criteria.
• Laboratory values as follows: Absolute neutrophil count (ANC) ≥1500/μL Hemoglobin (Hgb) ≥10 g/dL Platelets ≥100,000/L AST or ALT and alkaline phosphatase (ALP) must be <2.5 x ULN, or <5 x ULN in patients with liver metastases. Total bilirubin <1.5 x the institutional ULN Serum creatinine <1.5 x institutional ULN or calculated creatinine clearance ≥45 mL/min

Patients from Part 1 who have HER2 overexpression/activation identified by the PRO Onc Assay may enter the treatment portion of Part 2, if they meet all Part 2 eligibility criteria.

• Life expectancy of ≥ 12 weeks.
• Patient must be accessible for treatment and follow-up.
• Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.

Part II

• Women with HER2-negative breast cancer, as defined by FISH testing. (FISH testing may have been performed on the primary tumor, or subsequently on a biopsy of a metastatic lesion.)
• Patients should be currently receiving chemotherapy, or scheduled to start chemotherapy, for HER2-negative metastatic breast cancer.
• Patients who are ER/PR positive or negative are eligible. ER/PR positive patients should be refractory to hormonal therapy, or not good candidates for hormonal therapy due to clinical features.
• ECOG performance status of 0, 1 or 2.
• Adequate recovery from recent surgery; ≥ 1 week must have elapsed from the time of a minor surgery; ≥ 4 weeks must have elapsed from the time of a major surgery.
• Patients must have measurable disease per RECIST criteria.
• Laboratory values as follows:
• Absolute neutrophil count (ANC) ≥1500/μL
• Hemoglobin (Hgb) ≥10 g/dL
• Platelets ≥100,000/uL
• AST or ALT and alkaline phosphatase (ALP) must be <2.5 x ULN, or <5 x ULN in patients with liver metastases.
• Total bilirubin <1.5 x the institutional ULN
• Serum creatinine <1.5 x institutional ULN or calculated creatinine clearance ≥45 mL/min
• Life expectancy of ≥ 12 weeks.
• Patient must be accessible for treatment and follow-up.
• Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.
• Patients who are eligible for HER2-targeted treatment will begin this treatment at the first time a treatment change is necessary (i.e. at the next progression of metastatic breast cancer). This may occur immediately after PRO Onc assay results are received, or may be several months later, for patients responding well to their current chemotherapy.
• Patients must continue to meet all inclusion and exclusion criteria for the Part 2 screening population at the time they are ready to start HER2-targeted treatment.
• Ejection fraction ≥ 50%, as measured by echocardiogram (ECHO) or MUGA.

Exclusion Criteria

Part I:

• Patients currently responding to hormonal therapy.
• Previous treatment with any HER2-targeted agent.
• Patients with meningeal metastases.
• Patients who are not considered likely candidates for subseque