{
    "info": {
        "nct_id": "NCT00432172",
        "official_title": "\"A Randomized Multicenter Phase II Trial to Evaluate the Effectiveness of Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients\"",
        "inclusion_criteria": "* Written informed consent.\n* Breast cancer with histological diagnosis.\n* Negative Human Epidermal Growth Factor Receptor 2 (HER2) tumours defined as immunohistochemistry (IHQ) 0,1+.\n* No evidence of suspicion of metastatic disease.\n* Age >= 18 years old.\n* Performance status (Karnofsky index) >= 80 (ECOG 0,1).\n* Adequate cardiac function by ECG in the previous 12 weeks.\n* Hematology: neutrophils >= 1,5 x10^9/l; platelets >= 100 x10^9/l; hemoglobin >= 10 g/dl.\n* Adequate hepatic function: total bilirubin <= 1x Upper Normal Limit (UNL); Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) <= 2.5 x UNL; alkaline phosphatase <= 2.5 x UNL.\n* Adequate renal function: creatinine <= 1 x UNL; creatinine clearance >= 60 ml/min.\n* Patients able to comply with study treatment and follow-up.\n* Negative pregnancy test in the previous 14 days.\nHealthy volunteers allowed\nMust be FEMALE\nMust have minimum age of 18 Years",
        "exclusion_criteria": "* HER2 positive tumours (defined as IHQ 3+ or positive fluorescence in situ hybridization [FISH]).\n* Prior systemic therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).\n* Prior treatment with anthracyclines or taxanes (paclitaxel, docetaxel) for any previous malignancy.\n* Prior radiotherapy for breast cancer.\n* Bilateral invasive breast cancer.\n* Pregnant or lactating women.\n* Previous grade >= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria [NCICTC]).\n* Other serious comorbidities: congestive heart failure or unstable angina; prior history of myocardial infarction in previous year; uncontrolled hypertension (HT); high risk arrhythmias; history of significant neurological or psychiatric disorders; uncontrolled active infection; active peptic ulcer; unstable diabetes mellitus; dyspnea at rest; or chronic therapy with oxygen.\n* Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.\n* Chronic treatment with corticosteroids.\n* Contraindications for administration of corticosteroids.\n* Concomitant treatment with other therapy for cancer.\n* Males.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "* Written informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Written informed consent.",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Breast cancer with histological diagnosis.",
            "criterions": [
                {
                    "exact_snippets": "Breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "histological diagnosis",
                    "criterion": "histological diagnosis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Negative Human Epidermal Growth Factor Receptor 2 (HER2) tumours defined as immunohistochemistry (IHQ) 0,1+.",
            "criterions": [
                {
                    "exact_snippets": "Negative Human Epidermal Growth Factor Receptor 2 (HER2) tumours",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "defined as immunohistochemistry (IHQ) 0,1+",
                    "criterion": "immunohistochemistry (IHQ) score",
                    "requirements": [
                        {
                            "requirement_type": "score",
                            "expected_value": [
                                "0",
                                "1+"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* No evidence of suspicion of metastatic disease.",
            "criterions": [
                {
                    "exact_snippets": "No evidence of suspicion of metastatic disease",
                    "criterion": "metastatic disease",
                    "requirements": [
                        {
                            "requirement_type": "suspicion",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Age >= 18 years old.",
            "criterions": [
                {
                    "exact_snippets": "Age >= 18 years old",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Performance status (Karnofsky index) >= 80 (ECOG 0,1).",
            "criterions": [
                {
                    "exact_snippets": "Performance status (Karnofsky index) >= 80",
                    "criterion": "Karnofsky index",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 80,
                                "unit": "N/A"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ECOG 0,1",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "value",
                            "expected_value": [
                                "0",
                                "1"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate cardiac function by ECG in the previous 12 weeks.",
            "criterions": [
                {
                    "exact_snippets": "Adequate cardiac function by ECG",
                    "criterion": "cardiac function",
                    "requirements": [
                        {
                            "requirement_type": "assessment method",
                            "expected_value": "ECG"
                        },
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "in the previous 12 weeks",
                    "criterion": "cardiac function assessment timing",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "weeks"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Hematology: neutrophils >= 1,5 x10^9/l; platelets >= 100 x10^9/l; hemoglobin >= 10 g/dl.",
            "criterions": [
                {
                    "exact_snippets": "neutrophils >= 1,5 x10^9/l",
                    "criterion": "neutrophils",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1.5,
                                "unit": "x10^9/l"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "platelets >= 100 x10^9/l",
                    "criterion": "platelets",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 100,
                                "unit": "x10^9/l"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hemoglobin >= 10 g/dl",
                    "criterion": "hemoglobin",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 10,
                                "unit": "g/dl"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate hepatic function: total bilirubin <= 1x Upper Normal Limit (UNL); Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) <= 2.5 x UNL; alkaline phosphatase <= 2.5 x UNL.",
            "criterions": [
                {
                    "exact_snippets": "total bilirubin <= 1x Upper Normal Limit (UNL)",
                    "criterion": "total bilirubin",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "x UNL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Aspartate aminotransferase (AST) (SGOT) ... <= 2.5 x UNL",
                    "criterion": "Aspartate aminotransferase (AST) (SGOT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x UNL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Alanine aminotransferase (ALT) (SGPT) <= 2.5 x UNL",
                    "criterion": "Alanine aminotransferase (ALT) (SGPT)",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x UNL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "alkaline phosphatase <= 2.5 x UNL",
                    "criterion": "alkaline phosphatase",
                    "requirements": [
                        {
                            "requirement_type": "level",
                            "expected_value": {
                                "operator": "<=",
                                "value": 2.5,
                                "unit": "x UNL"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Adequate renal function: creatinine <= 1 x UNL; creatinine clearance >= 60 ml/min.",
            "criterions": [
                {
                    "exact_snippets": "Adequate renal function: creatinine <= 1 x UNL",
                    "criterion": "creatinine level",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "x UNL"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate renal function: ... creatinine clearance >= 60 ml/min.",
                    "criterion": "creatinine clearance",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": {
                                "operator": ">=",
                                "value": 60,
                                "unit": "ml/min"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Patients able to comply with study treatment and follow-up.",
            "criterions": [
                {
                    "exact_snippets": "Patients able to comply with study treatment",
                    "criterion": "compliance with study treatment",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients able to comply with ... follow-up",
                    "criterion": "compliance with follow-up",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Negative pregnancy test in the previous 14 days.",
            "criterions": [
                {
                    "exact_snippets": "Negative pregnancy test",
                    "criterion": "pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "in the previous 14 days",
                    "criterion": "pregnancy test timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<=",
                                "value": 14,
                                "unit": "days"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must be FEMALE",
            "criterions": [
                {
                    "exact_snippets": "Must be FEMALE",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "female"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Must have minimum age of 18 Years",
            "criterions": [
                {
                    "exact_snippets": "minimum age of 18 Years",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "Years"
                            }
                        }
                    ]
                }
            ]
        }
    ],
    "exclusion_lines": [
        {
            "line": "* HER2 positive tumours (defined as IHQ 3+ or positive fluorescence in situ hybridization [FISH]).",
            "criterions": [
                {
                    "exact_snippets": "HER2 positive tumours (defined as IHQ 3+ or positive fluorescence in situ hybridization [FISH])",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "positive"
                        },
                        {
                            "requirement_type": "definition",
                            "expected_value": [
                                "IHQ 3+",
                                "positive fluorescence in situ hybridization [FISH]"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior systemic therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).",
            "criterions": [
                {
                    "exact_snippets": "Prior systemic therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy)",
                    "criterion": "prior systemic therapy for breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "immunotherapy",
                                "hormonotherapy",
                                "chemotherapy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior treatment with anthracyclines or taxanes (paclitaxel, docetaxel) for any previous malignancy.",
            "criterions": [
                {
                    "exact_snippets": "Prior treatment with anthracyclines",
                    "criterion": "prior treatment with anthracyclines",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior treatment with ... taxanes (paclitaxel, docetaxel)",
                    "criterion": "prior treatment with taxanes",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Prior radiotherapy for breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Prior radiotherapy for breast cancer.",
                    "criterion": "radiotherapy",
                    "requirements": [
                        {
                            "requirement_type": "prior treatment",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Prior radiotherapy for breast cancer.",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Bilateral invasive breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Bilateral invasive breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "laterality",
                            "expected_value": "bilateral"
                        },
                        {
                            "requirement_type": "invasiveness",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Pregnant or lactating women.",
            "criterions": [
                {
                    "exact_snippets": "Pregnant",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "lactating",
                    "criterion": "lactation",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous grade >= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria [NCICTC]).",
            "criterions": [
                {
                    "exact_snippets": "Previous grade >= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria [NCICTC])",
                    "criterion": "motor or sensorial neurotoxicity",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 2,
                                "unit": "grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Other serious comorbidities: congestive heart failure or unstable angina; prior history of myocardial infarction in previous year; uncontrolled hypertension (HT); high risk arrhythmias; history of significant neurological or psychiatric disorders; uncontrolled active infection; active peptic ulcer; unstable diabetes mellitus; dyspnea at rest; or chronic therapy with oxygen.",
            "criterions": [
                {
                    "exact_snippets": "congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable angina",
                    "criterion": "unstable angina",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "prior history of myocardial infarction in previous year",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 1,
                                "unit": "year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled hypertension (HT)",
                    "criterion": "hypertension",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "high risk arrhythmias",
                    "criterion": "high risk arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "history of significant neurological or psychiatric disorders",
                    "criterion": "neurological or psychiatric disorders",
                    "requirements": [
                        {
                            "requirement_type": "significance",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "uncontrolled active infection",
                    "criterion": "active infection",
                    "requirements": [
                        {
                            "requirement_type": "control",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "active peptic ulcer",
                    "criterion": "peptic ulcer",
                    "requirements": [
                        {
                            "requirement_type": "activity",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "unstable diabetes mellitus",
                    "criterion": "diabetes mellitus",
                    "requirements": [
                        {
                            "requirement_type": "stability",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "dyspnea at rest",
                    "criterion": "dyspnea at rest",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "chronic therapy with oxygen",
                    "criterion": "chronic therapy with oxygen",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.",
            "criterions": [
                {
                    "exact_snippets": "Previous or current history of neoplasms different from breast cancer",
                    "criterion": "history of neoplasms",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "different from breast cancer"
                        }
                    ]
                },
                {
                    "exact_snippets": "except for skin carcinoma",
                    "criterion": "history of neoplasms",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "skin carcinoma"
                        }
                    ]
                },
                {
                    "exact_snippets": "except for ... cervical in situ carcinoma",
                    "criterion": "history of neoplasms",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": "cervical in situ carcinoma"
                        }
                    ]
                },
                {
                    "exact_snippets": "except for ... any other tumor curatively treated and without recurrence in the last 10 years",
                    "criterion": "history of neoplasms",
                    "requirements": [
                        {
                            "requirement_type": "treatment status",
                            "expected_value": "curatively treated"
                        },
                        {
                            "requirement_type": "recurrence",
                            "expected_value": {
                                "operator": "<",
                                "value": 10,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "ductal in situ carcinoma in the same breast",
                    "criterion": "ductal in situ carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "location",
                            "expected_value": "same breast"
                        }
                    ]
                },
                {
                    "exact_snippets": "lobular in situ carcinoma",
                    "criterion": "lobular in situ carcinoma",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Chronic treatment with corticosteroids.",
            "criterions": [
                {
                    "exact_snippets": "Chronic treatment with corticosteroids",
                    "criterion": "corticosteroid treatment",
                    "requirements": [
                        {
                            "requirement_type": "duration",
                            "expected_value": "chronic"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Contraindications for administration of corticosteroids.",
            "criterions": [
                {
                    "exact_snippets": "Contraindications for administration of corticosteroids",
                    "criterion": "corticosteroid administration",
                    "requirements": [
                        {
                            "requirement_type": "contraindications",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Concomitant treatment with other therapy for cancer.",
            "criterions": [
                {
                    "exact_snippets": "Concomitant treatment with other therapy for cancer.",
                    "criterion": "concomitant treatment",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Males.",
            "criterions": [
                {
                    "exact_snippets": "Males",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "expected_value",
                            "expected_value": "male"
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}