{
    "info": {
        "nct_id": "NCT06446882",
        "official_title": "Diagnostic HER2DX-guided Treatment for patIents wIth Early-stage HER2-positive Breast Cancer",
        "inclusion_criteria": "1. Signed informed consent must be obtained prior to any trial-specific procedure. Note: Candidate patients in France must be affiliated to a Social Security System (or equivalent).\n2. Male/female patients who are at least 18 years of age on the day of signing informed consent.\n3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.\n4. Eligible for any of the following drugs: taxane, carboplatin, trastuzumab, pertuzumab and T-DM1 therapy.\n5. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast untreated and recently diagnosed.\n6. Stage at presentation: cT1 cN1-2 or cT2-3 cN0-2 as determined by AJCC staging system, 8th edition (specifically in accordance with Anatomic Stage group rules).\n\n   Note: Axillary lymph node status must be assessed by fine needle biopsy or core biopsy. This procedure at screening will be omitted if there is no suspicion for positive axillary lymph node(s) radiographically or if a pathological report of suspicious lymph nodes of the results of a fine needle biopsy or core biopsy is available prior to the screening period.\n7. Absence of distant metastasis (i.e., cM0).\n8. Patients with multifocal tumors (more than one mass confined to the same quadrant as primary tumor) are eligible provided at least one focus is sampled and locally confirmed as HER2-positive.\n9. Patients with multicentric tumors (multiple tumors involving more than one quadrant) are eligible provided all discrete lesions are sampled and locally confirmed as HER2-positive.\n\n   Note: In patients with multifocal or multicentric breast cancer, the largest lesion should be measured to determine T stage and to performe the HER2DX test.\n10. HER2 positivity defined as either of the following: IHC 3+ or HER2 2+/ ISH positive as per most recent ASCO- CAP guideline according to the local laboratory as determined on the most recently analyzed tissue sample.\n11. ER/PR status determined local based on pretreatment breast biopsy material according to the most recent ASCO/CAP guidelines.\n12. Candidates for neoadjuvant treatment.\n13. Patient agreement to undergo appropriate surgical management, including axillary lymph node surgery and partial or total mastectomy, after completion of neoadjuvant treatment\n14. Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans.\n15. Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary tumor in the breast for diagnostic HER2DX test. The tumor tissue should be of good quality based on total and viable tumor content and must be evaluated centrally for quality prior to enrollment. Archival tumor tissue or ex professo biopsy are acceptable.\n16. Adequate hematologic and end-organ function.\n17. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:\n\n    * Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last. Women must refrain from donating eggs during this same period.\n    * A woman is of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (> 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.\n    * Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, copper intrauterine devices, hormonal contraceptives that inhibit ovulation, and hormone-releasing intrauterine devices in women with hormone receptor-negative tumors only; the use of hormonal contraceptives and hormone releasing intrauterine devices are prohibited in women with hormone receptor-positive tumors.\n    * The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\n18. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:\n\n    * With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last. Men must refrain from donating sperm during this same period. Male patients are encouraged to seek advice regarding cryoconservation of sperm prior to commencing study treatment because of the possibility of infertility with CT.\n    * With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last to avoid exposing the embryo.\n    * The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
        "exclusion_criteria": "1. Stage IV (metastatic) breast cancer.\n2. Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, carboplatin, T-DM1, docetaxel or paclitaxel.\n3. Patients with synchronous bilateral invasive breast cancer.\n4. Prior systemic therapy for treatment of breast cancer.\n5. Ulcerating or inflammatory breast cancer.\n6. Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes.\n7. Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy.\n8. Patients with a history of previous breast cancer are excluded. Patients with a history of any other cancers (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years are excluded. For patients with a history of other non-breast cancerscancerscancers within 3 years and considered of low risk of recurrence per investigator's judgment (for example, papillary thyroid cancer treated with surgery), eligibility is to be discussed with the Sponsor.\n9. Cardiopulmonary dysfunction as defined by any of the following prior to randomization:\n\n   * History of congestive heart failure of any classification.\n   * Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease.\n   * High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block]).\n   * Significant symptoms (Grade > 1) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia.\n   * Myocardial infarction within 12 months prior to randomization.\n   * Evidence of transmural infarction on ECG.\n   * Requirement for oxygen therapy.\n   * Dyspnea at rest.\n10. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the Study.\n11. Severe infection within 4 weeks prior to initiation of Study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.\n12. History of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the Study, the evaluation of response, or with consent procedure.\n13. Pregnancy or breastfeeding, or intention of becoming pregnant during Study treatment or within 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last.\n\n    Note: Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of Study treatment.\n14. Persons deprived of their liberty or under protective custody or guardianship.\n15. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.",
        "miscellaneous_criteria": ""
    },
    "inclusion_lines": [
        {
            "line": "1. Signed informed consent must be obtained prior to any trial-specific procedure. Note: Candidate patients in France must be affiliated to a Social Security System (or equivalent).",
            "criterions": [
                {
                    "exact_snippets": "Signed informed consent must be obtained",
                    "criterion": "informed consent",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Candidate patients in France must be affiliated to a Social Security System (or equivalent)",
                    "criterion": "affiliation to a Social Security System",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Male/female patients who are at least 18 years of age on the day of signing informed consent.",
            "criterions": [
                {
                    "exact_snippets": "Male/female patients",
                    "criterion": "gender",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": [
                                "male",
                                "female"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "at least 18 years of age",
                    "criterion": "age",
                    "requirements": [
                        {
                            "requirement_type": "minimum age",
                            "expected_value": {
                                "operator": ">=",
                                "value": 18,
                                "unit": "years"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.",
            "criterions": [
                {
                    "exact_snippets": "Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2",
                    "criterion": "ECOG performance status",
                    "requirements": [
                        {
                            "requirement_type": "range",
                            "expected_value": {
                                "comparisons": [
                                    {
                                        "operator": ">=",
                                        "value": 0,
                                        "unit": "N/A"
                                    },
                                    {
                                        "operator": "<=",
                                        "value": 2,
                                        "unit": "N/A"
                                    }
                                ]
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Eligible for any of the following drugs: taxane, carboplatin, trastuzumab, pertuzumab and T-DM1 therapy.",
            "criterions": [
                {
                    "exact_snippets": "Eligible for any of the following drugs: taxane, carboplatin, trastuzumab, pertuzumab and T-DM1 therapy.",
                    "criterion": "drug eligibility",
                    "requirements": [
                        {
                            "requirement_type": "eligibility",
                            "expected_value": [
                                "taxane",
                                "carboplatin",
                                "trastuzumab",
                                "pertuzumab",
                                "T-DM1 therapy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Histologically confirmed non-metastatic primary invasive adenocarcinoma of the breast untreated and recently diagnosed.",
            "criterions": [
                {
                    "exact_snippets": "Histologically confirmed",
                    "criterion": "histological confirmation",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "non-metastatic",
                    "criterion": "metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "primary invasive adenocarcinoma of the breast",
                    "criterion": "primary invasive adenocarcinoma of the breast",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "untreated",
                    "criterion": "treatment status",
                    "requirements": [
                        {
                            "requirement_type": "treatment",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "recently diagnosed",
                    "criterion": "diagnosis timing",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "recent"
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Stage at presentation: cT1 cN1-2 or cT2-3 cN0-2 as determined by AJCC staging system, 8th edition (specifically in accordance with Anatomic Stage group rules).",
            "criterions": [
                {
                    "exact_snippets": "Stage at presentation: cT1 cN1-2 or cT2-3 cN0-2 ... AJCC staging system, 8th edition",
                    "criterion": "stage at presentation",
                    "requirements": [
                        {
                            "requirement_type": "AJCC stage",
                            "expected_value": [
                                "cT1 cN1-2",
                                "cT2-3 cN0-2"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "Note: Axillary lymph node status must be assessed by fine needle biopsy or core biopsy. This procedure at screening will be omitted if there is no suspicion for positive axillary lymph node(s) radiographically or if a pathological report of suspicious lymph nodes of the results of a fine needle biopsy or core biopsy is available prior to the screening period.",
            "criterions": [
                {
                    "exact_snippets": "Axillary lymph node status must be assessed by fine needle biopsy or core biopsy.",
                    "criterion": "axillary lymph node status",
                    "requirements": [
                        {
                            "requirement_type": "assessment method",
                            "expected_value": [
                                "fine needle biopsy",
                                "core biopsy"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "This procedure at screening will be omitted if there is no suspicion for positive axillary lymph node(s) radiographically",
                    "criterion": "suspicion for positive axillary lymph node(s)",
                    "requirements": [
                        {
                            "requirement_type": "radiographic suspicion",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "if a pathological report of suspicious lymph nodes of the results of a fine needle biopsy or core biopsy is available prior to the screening period.",
                    "criterion": "pathological report of suspicious lymph nodes",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Absence of distant metastasis (i.e., cM0).",
            "criterions": [
                {
                    "exact_snippets": "Absence of distant metastasis (i.e., cM0)",
                    "criterion": "distant metastasis",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients with multifocal tumors (more than one mass confined to the same quadrant as primary tumor) are eligible provided at least one focus is sampled and locally confirmed as HER2-positive.",
            "criterions": [
                {
                    "exact_snippets": "multifocal tumors (more than one mass confined to the same quadrant as primary tumor)",
                    "criterion": "multifocal tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "at least one focus is sampled",
                    "criterion": "focus sampling",
                    "requirements": [
                        {
                            "requirement_type": "quantity",
                            "expected_value": {
                                "operator": ">=",
                                "value": 1,
                                "unit": "focus"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "locally confirmed as HER2-positive",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "HER2-positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Patients with multicentric tumors (multiple tumors involving more than one quadrant) are eligible provided all discrete lesions are sampled and locally confirmed as HER2-positive.",
            "criterions": [
                {
                    "exact_snippets": "multicentric tumors (multiple tumors involving more than one quadrant)",
                    "criterion": "multicentric tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "all discrete lesions are sampled",
                    "criterion": "discrete lesions",
                    "requirements": [
                        {
                            "requirement_type": "sampling",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "locally confirmed as HER2-positive",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "confirmation",
                            "expected_value": "HER2-positive"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. HER2 positivity defined as either of the following: IHC 3+ or HER2 2+/ ISH positive as per most recent ASCO- CAP guideline according to the local laboratory as determined on the most recently analyzed tissue sample.",
            "criterions": [
                {
                    "exact_snippets": "HER2 positivity defined as either of the following: IHC 3+ or HER2 2+/ ISH positive",
                    "criterion": "HER2 status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": [
                                "IHC 3+",
                                "HER2 2+/ ISH positive"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "as per most recent ASCO- CAP guideline",
                    "criterion": "guideline adherence",
                    "requirements": [
                        {
                            "requirement_type": "adherence",
                            "expected_value": "most recent ASCO- CAP guideline"
                        }
                    ]
                },
                {
                    "exact_snippets": "according to the local laboratory",
                    "criterion": "local laboratory determination",
                    "requirements": [
                        {
                            "requirement_type": "determination",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "as determined on the most recently analyzed tissue sample",
                    "criterion": "tissue sample analysis",
                    "requirements": [
                        {
                            "requirement_type": "recency",
                            "expected_value": "most recently analyzed"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. ER/PR status determined local based on pretreatment breast biopsy material according to the most recent ASCO/CAP guidelines.",
            "criterions": [
                {
                    "exact_snippets": "ER/PR status determined local based on pretreatment breast biopsy material",
                    "criterion": "ER/PR status",
                    "requirements": [
                        {
                            "requirement_type": "determination",
                            "expected_value": "local based on pretreatment breast biopsy material"
                        }
                    ]
                },
                {
                    "exact_snippets": "according to the most recent ASCO/CAP guidelines",
                    "criterion": "ASCO/CAP guidelines",
                    "requirements": [
                        {
                            "requirement_type": "adherence",
                            "expected_value": "most recent"
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. Candidates for neoadjuvant treatment.",
            "criterions": [
                {
                    "exact_snippets": "Candidates for neoadjuvant treatment.",
                    "criterion": "neoadjuvant treatment candidacy",
                    "requirements": [
                        {
                            "requirement_type": "candidacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Patient agreement to undergo appropriate surgical management, including axillary lymph node surgery and partial or total mastectomy, after completion of neoadjuvant treatment",
            "criterions": [
                {
                    "exact_snippets": "Patient agreement to undergo appropriate surgical management",
                    "criterion": "surgical management agreement",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "axillary lymph node surgery",
                    "criterion": "axillary lymph node surgery",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": "axillary lymph node surgery"
                        }
                    ]
                },
                {
                    "exact_snippets": "partial or total mastectomy",
                    "criterion": "mastectomy",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": [
                                "partial mastectomy",
                                "total mastectomy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Baseline left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans.",
            "criterions": [
                {
                    "exact_snippets": "Baseline left ventricular ejection fraction (LVEF) ≥ 50%",
                    "criterion": "left ventricular ejection fraction (LVEF)",
                    "requirements": [
                        {
                            "requirement_type": "baseline measurement",
                            "expected_value": true
                        },
                        {
                            "requirement_type": "value",
                            "expected_value": {
                                "operator": ">=",
                                "value": 50,
                                "unit": "%"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "measured by echocardiogram (ECHO)",
                    "criterion": "echocardiogram (ECHO)",
                    "requirements": [
                        {
                            "requirement_type": "measurement method",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "measured by ... multiple-gated acquisition (MUGA) scans",
                    "criterion": "multiple-gated acquisition (MUGA) scans",
                    "requirements": [
                        {
                            "requirement_type": "measurement method",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary tumor in the breast for diagnostic HER2DX test. The tumor tissue should be of good quality based on total and viable tumor content and must be evaluated centrally for quality prior to enrollment. Archival tumor tissue or ex professo biopsy are acceptable.",
            "criterions": [
                {
                    "exact_snippets": "Availability of pre-treatment tumor tissue sample of FFPE tumor block from primary tumor in the breast",
                    "criterion": "pre-treatment tumor tissue sample",
                    "requirements": [
                        {
                            "requirement_type": "availability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "The tumor tissue should be of good quality based on total and viable tumor content",
                    "criterion": "tumor tissue quality",
                    "requirements": [
                        {
                            "requirement_type": "quality",
                            "expected_value": "good"
                        }
                    ]
                },
                {
                    "exact_snippets": "must be evaluated centrally for quality prior to enrollment",
                    "criterion": "central evaluation for quality",
                    "requirements": [
                        {
                            "requirement_type": "evaluation",
                            "expected_value": "central"
                        }
                    ]
                },
                {
                    "exact_snippets": "Archival tumor tissue or ex professo biopsy are acceptable",
                    "criterion": "source of tumor tissue",
                    "requirements": [
                        {
                            "requirement_type": "source",
                            "expected_value": [
                                "archival tumor tissue",
                                "ex professo biopsy"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "16. Adequate hematologic and end-organ function.",
            "criterions": [
                {
                    "exact_snippets": "Adequate hematologic ... function.",
                    "criterion": "hematologic function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Adequate ... end-organ function.",
                    "criterion": "end-organ function",
                    "requirements": [
                        {
                            "requirement_type": "adequacy",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "17. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:",
            "criterions": [
                {
                    "exact_snippets": "women of childbearing potential",
                    "criterion": "childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "agreement to remain abstinent (refrain from heterosexual intercourse)",
                    "criterion": "abstinence from heterosexual intercourse",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "use contraceptive methods",
                    "criterion": "contraceptive methods",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "agreement to refrain from donating eggs",
                    "criterion": "egg donation",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last. Women must refrain from donating eggs during this same period.",
            "criterions": [
                {
                    "exact_snippets": "Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last.",
                    "criterion": "contraceptive methods",
                    "requirements": [
                        {
                            "requirement_type": "failure rate",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "% per year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Women must refrain from donating eggs during this same period.",
                    "criterion": "egg donation",
                    "requirements": [
                        {
                            "requirement_type": "refrain",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* A woman is of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (> 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.",
            "criterions": [
                {
                    "exact_snippets": "postmenarcheal",
                    "criterion": "postmenarcheal status",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "postmenopausal state (> 12 continuous months of amenorrhea with no identified cause other than menopause)",
                    "criterion": "postmenopausal state",
                    "requirements": [
                        {
                            "requirement_type": "absence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "surgical sterilization (removal of ovaries and/or uterus)",
                    "criterion": "surgical sterilization",
                    "requirements": [
                        {
                            "requirement_type": "absence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, copper intrauterine devices, hormonal contraceptives that inhibit ovulation, and hormone-releasing intrauterine devices in women with hormone receptor-negative tumors only; the use of hormonal contraceptives and hormone releasing intrauterine devices are prohibited in women with hormone receptor-positive tumors.",
            "criterions": [
                {
                    "exact_snippets": "contraceptive methods with a failure rate of < 1% per year",
                    "criterion": "contraceptive method failure rate",
                    "requirements": [
                        {
                            "requirement_type": "failure rate",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "% per year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "hormonal contraceptives and hormone releasing intrauterine devices are prohibited in women with hormone receptor-positive tumors",
                    "criterion": "hormonal contraceptives and hormone releasing intrauterine devices",
                    "requirements": [
                        {
                            "requirement_type": "prohibition",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "hormonal contraceptives and hormone releasing intrauterine devices are prohibited in women with hormone receptor-positive tumors",
                    "criterion": "hormone receptor-positive tumors",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.",
            "criterions": [
                {
                    "exact_snippets": "reliability of sexual abstinence should be evaluated",
                    "criterion": "sexual abstinence",
                    "requirements": [
                        {
                            "requirement_type": "reliability",
                            "expected_value": "evaluated"
                        }
                    ]
                },
                {
                    "exact_snippets": "Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception",
                    "criterion": "contraception methods",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": [
                                "calendar",
                                "ovulation",
                                "symptothermal",
                                "postovulation",
                                "withdrawal"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "18. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below:",
            "criterions": [
                {
                    "exact_snippets": "For men: agreement to remain abstinent (refrain from heterosexual intercourse)",
                    "criterion": "abstinence from heterosexual intercourse",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "For men: ... use contraceptive measures",
                    "criterion": "use of contraceptive measures",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "For men: ... agreement to refrain from donating sperm",
                    "criterion": "refrain from donating sperm",
                    "requirements": [
                        {
                            "requirement_type": "agreement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last. Men must refrain from donating sperm during this same period. Male patients are encouraged to seek advice regarding cryoconservation of sperm prior to commencing study treatment because of the possibility of infertility with CT.",
            "criterions": [
                {
                    "exact_snippets": "female partner of childbearing potential who is not pregnant",
                    "criterion": "female partner's pregnancy status",
                    "requirements": [
                        {
                            "requirement_type": "pregnancy status",
                            "expected_value": "not pregnant"
                        }
                    ]
                },
                {
                    "exact_snippets": "men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year",
                    "criterion": "contraceptive method effectiveness",
                    "requirements": [
                        {
                            "requirement_type": "failure rate",
                            "expected_value": {
                                "operator": "<",
                                "value": 1,
                                "unit": "% per year"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method",
                    "criterion": "contraceptive method",
                    "requirements": [
                        {
                            "requirement_type": "use",
                            "expected_value": [
                                "abstinence",
                                "condom",
                                "additional contraceptive method"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "Men must refrain from donating sperm during this same period",
                    "criterion": "sperm donation",
                    "requirements": [
                        {
                            "requirement_type": "refrain from",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "Male patients are encouraged to seek advice regarding cryoconservation of sperm prior to commencing study treatment",
                    "criterion": "cryoconservation of sperm",
                    "requirements": [
                        {
                            "requirement_type": "advice",
                            "expected_value": "encouraged"
                        }
                    ]
                },
                {
                    "exact_snippets": "possibility of infertility with CT",
                    "criterion": "infertility risk",
                    "requirements": [
                        {
                            "requirement_type": "risk",
                            "expected_value": "possibility"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last to avoid exposing the embryo.",
            "criterions": [
                {
                    "exact_snippets": "With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last to avoid exposing the embryo.",
                    "criterion": "men with a pregnant female partner",
                    "requirements": [
                        {
                            "requirement_type": "behavior",
                            "expected_value": "remain abstinent or use a condom during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last"
                        }
                    ]
                }
            ]
        },
        {
            "line": "* The reliability of sexual abstinence should be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.",
            "criterions": [
                {
                    "exact_snippets": "reliability of sexual abstinence should be evaluated",
                    "criterion": "sexual abstinence",
                    "requirements": [
                        {
                            "requirement_type": "reliability",
                            "expected_value": "evaluated"
                        }
                    ]
                },
                {
                    "exact_snippets": "Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception",
                    "criterion": "contraception methods",
                    "requirements": [
                        {
                            "requirement_type": "acceptability",
                            "expected_value": [
                                "periodic abstinence",
                                "withdrawal"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "Healthy volunteers allowed",
            "criterions": [
                {
                    "exact_snippets": "Healthy volunteers allowed",
                    "criterion": "volunteer health status",
                    "requirements": [
                        {
                            "requirement_type": "status",
                            "expected_value": "healthy"
                        }
                    ]
                }
            ]
        },
        {
            "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": "1. Stage IV (metastatic) breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Stage IV (metastatic) breast cancer",
                    "criterion": "breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "stage",
                            "expected_value": "IV"
                        },
                        {
                            "requirement_type": "metastasis",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "2. Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, carboplatin, T-DM1, docetaxel or paclitaxel.",
            "criterions": [
                {
                    "exact_snippets": "Known hypersensitivity to any of the excipients of trastuzumab, pertuzumab, carboplatin, T-DM1, docetaxel or paclitaxel.",
                    "criterion": "hypersensitivity to excipients",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "3. Patients with synchronous bilateral invasive breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "synchronous bilateral invasive breast cancer",
                    "criterion": "synchronous bilateral invasive breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "4. Prior systemic therapy for treatment of breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Prior systemic therapy for treatment of breast cancer.",
                    "criterion": "prior systemic therapy",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "treatment of breast cancer"
                        }
                    ]
                }
            ]
        },
        {
            "line": "5. Ulcerating or inflammatory breast cancer.",
            "criterions": [
                {
                    "exact_snippets": "Ulcerating ... breast cancer",
                    "criterion": "ulcerating breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "inflammatory breast cancer",
                    "criterion": "inflammatory breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "6. Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes.",
            "criterions": [
                {
                    "exact_snippets": "Undergone incisional and/or excisional biopsy of primary tumor",
                    "criterion": "biopsy of primary tumor",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": "incisional and/or excisional"
                        }
                    ]
                },
                {
                    "exact_snippets": "Undergone incisional and/or excisional biopsy of ... axillary lymph nodes",
                    "criterion": "biopsy of axillary lymph nodes",
                    "requirements": [
                        {
                            "requirement_type": "procedure",
                            "expected_value": "incisional and/or excisional"
                        }
                    ]
                }
            ]
        },
        {
            "line": "7. Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy.",
            "criterions": [
                {
                    "exact_snippets": "Sentinel lymph node procedure",
                    "criterion": "sentinel lymph node procedure",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "prior to initiation of neoadjuvant therapy"
                        }
                    ]
                },
                {
                    "exact_snippets": "axillary lymph node dissection",
                    "criterion": "axillary lymph node dissection",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "prior to initiation of neoadjuvant therapy"
                        }
                    ]
                }
            ]
        },
        {
            "line": "8. Patients with a history of previous breast cancer are excluded. Patients with a history of any other cancers (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years are excluded. For patients with a history of other non-breast cancerscancerscancers within 3 years and considered of low risk of recurrence per investigator's judgment (for example, papillary thyroid cancer treated with surgery), eligibility is to be discussed with the Sponsor.",
            "criterions": [
                {
                    "exact_snippets": "Patients with a history of previous breast cancer are excluded.",
                    "criterion": "history of previous breast cancer",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "Patients with a history of any other cancers (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years are excluded.",
                    "criterion": "history of other cancers",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        },
                        {
                            "requirement_type": "remission status",
                            "expected_value": "complete remission"
                        },
                        {
                            "requirement_type": "therapy duration",
                            "expected_value": {
                                "operator": ">=",
                                "value": 3,
                                "unit": "years"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "patients with a history of other non-breast cancerscancerscancers within 3 years and considered of low risk of recurrence per investigator's judgment",
                    "criterion": "history of other non-breast cancers",
                    "requirements": [
                        {
                            "requirement_type": "time since diagnosis",
                            "expected_value": {
                                "operator": "<=",
                                "value": 3,
                                "unit": "years"
                            }
                        },
                        {
                            "requirement_type": "risk of recurrence",
                            "expected_value": "low risk per investigator's judgment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "9. Cardiopulmonary dysfunction as defined by any of the following prior to randomization:",
            "criterions": [
                {
                    "exact_snippets": "Cardiopulmonary dysfunction",
                    "criterion": "cardiopulmonary dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* History of congestive heart failure of any classification.",
            "criterions": [
                {
                    "exact_snippets": "History of congestive heart failure",
                    "criterion": "congestive heart failure",
                    "requirements": [
                        {
                            "requirement_type": "history",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Angina pectoris requiring anti-anginal medication, serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality, or clinically significant valvular disease.",
            "criterions": [
                {
                    "exact_snippets": "Angina pectoris requiring anti-anginal medication",
                    "criterion": "angina pectoris",
                    "requirements": [
                        {
                            "requirement_type": "medication requirement",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "serious cardiac arrhythmia not controlled by adequate medication",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "control by medication",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "severe conduction abnormality",
                    "criterion": "conduction abnormality",
                    "requirements": [
                        {
                            "requirement_type": "severity",
                            "expected_value": "severe"
                        }
                    ]
                },
                {
                    "exact_snippets": "clinically significant valvular disease",
                    "criterion": "valvular disease",
                    "requirements": [
                        {
                            "requirement_type": "clinical significance",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate > 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block]).",
            "criterions": [
                {
                    "exact_snippets": "High-risk uncontrolled arrhythmias",
                    "criterion": "uncontrolled arrhythmias",
                    "requirements": [
                        {
                            "requirement_type": "risk level",
                            "expected_value": "high-risk"
                        }
                    ]
                },
                {
                    "exact_snippets": "atrial tachycardia with a heart rate > 100/min at rest",
                    "criterion": "atrial tachycardia",
                    "requirements": [
                        {
                            "requirement_type": "heart rate",
                            "expected_value": {
                                "operator": ">",
                                "value": 100,
                                "unit": "min"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "significant ventricular arrhythmia [ventricular tachycardia]",
                    "criterion": "ventricular arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "significance",
                            "expected_value": "significant"
                        }
                    ]
                },
                {
                    "exact_snippets": "higher-grade atrioventricular [AV]-block [second degree AV-block Type 2 [Mobitz 2] or third-degree AV-block]",
                    "criterion": "atrioventricular block",
                    "requirements": [
                        {
                            "requirement_type": "grade",
                            "expected_value": [
                                "second degree AV-block Type 2 [Mobitz 2]",
                                "third-degree AV-block"
                            ]
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Significant symptoms (Grade > 1) relating to left ventricular dysfunction, cardiac arrhythmia, or cardiac ischemia.",
            "criterions": [
                {
                    "exact_snippets": "Significant symptoms (Grade > 1) relating to left ventricular dysfunction",
                    "criterion": "left ventricular dysfunction",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Significant symptoms (Grade > 1) relating to ... cardiac arrhythmia",
                    "criterion": "cardiac arrhythmia",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "Grade"
                            }
                        }
                    ]
                },
                {
                    "exact_snippets": "Significant symptoms (Grade > 1) relating to ... cardiac ischemia",
                    "criterion": "cardiac ischemia",
                    "requirements": [
                        {
                            "requirement_type": "symptoms",
                            "expected_value": {
                                "operator": ">",
                                "value": 1,
                                "unit": "Grade"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Myocardial infarction within 12 months prior to randomization.",
            "criterions": [
                {
                    "exact_snippets": "Myocardial infarction within 12 months prior to randomization.",
                    "criterion": "myocardial infarction",
                    "requirements": [
                        {
                            "requirement_type": "time since event",
                            "expected_value": {
                                "operator": "<=",
                                "value": 12,
                                "unit": "months"
                            }
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Evidence of transmural infarction on ECG.",
            "criterions": [
                {
                    "exact_snippets": "Evidence of transmural infarction on ECG",
                    "criterion": "transmural infarction",
                    "requirements": [
                        {
                            "requirement_type": "evidence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Requirement for oxygen therapy.",
            "criterions": [
                {
                    "exact_snippets": "Requirement for oxygen therapy.",
                    "criterion": "oxygen therapy",
                    "requirements": [
                        {
                            "requirement_type": "requirement",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "* Dyspnea at rest.",
            "criterions": [
                {
                    "exact_snippets": "Dyspnea at rest",
                    "criterion": "dyspnea",
                    "requirements": [
                        {
                            "requirement_type": "condition",
                            "expected_value": "at rest"
                        }
                    ]
                }
            ]
        },
        {
            "line": "10. Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the Study.",
            "criterions": [
                {
                    "exact_snippets": "Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment",
                    "criterion": "major surgical procedure",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": {
                                "operator": "<",
                                "value": 4,
                                "unit": "weeks"
                            }
                        },
                        {
                            "requirement_type": "purpose",
                            "expected_value": "other than for diagnosis"
                        }
                    ]
                },
                {
                    "exact_snippets": "anticipation of need for a major surgical procedure during the Study",
                    "criterion": "anticipation of need for a major surgical procedure",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "during the Study"
                        }
                    ]
                }
            ]
        },
        {
            "line": "11. Severe infection within 4 weeks prior to initiation of Study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.",
            "criterions": [
                {
                    "exact_snippets": "Severe infection within 4 weeks prior to initiation of Study treatment",
                    "criterion": "severe infection",
                    "requirements": [
                        {
                            "requirement_type": "time frame",
                            "expected_value": "within 4 weeks prior to initiation of Study treatment"
                        }
                    ]
                },
                {
                    "exact_snippets": "hospitalization for complications of infection",
                    "criterion": "hospitalization for complications of infection",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "bacteremia",
                    "criterion": "bacteremia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "severe pneumonia",
                    "criterion": "severe pneumonia",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "12. History of significant co-morbidities that, in the judgment of the investigator, may interfere with the conduction of the Study, the evaluation of response, or with consent procedure.",
            "criterions": [
                {
                    "exact_snippets": "History of significant co-morbidities",
                    "criterion": "significant co-morbidities",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                }
            ]
        },
        {
            "line": "13. Pregnancy or breastfeeding, or intention of becoming pregnant during Study treatment or within 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last.",
            "criterions": [
                {
                    "exact_snippets": "Pregnancy",
                    "criterion": "pregnancy",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "breastfeeding",
                    "criterion": "breastfeeding",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": false
                        }
                    ]
                },
                {
                    "exact_snippets": "intention of becoming pregnant during Study treatment or within 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last",
                    "criterion": "intention of becoming pregnant",
                    "requirements": [
                        {
                            "requirement_type": "timeframe",
                            "expected_value": "during Study treatment or within 6 months after the final dose of paclitaxel, or 7 months after the final dose of trastuzumab, pertuzumab, or T-DM1, whichever occurs last"
                        }
                    ]
                }
            ]
        },
        {
            "line": "Note: Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to initiation of Study treatment.",
            "criterions": [
                {
                    "exact_snippets": "Women of childbearing potential",
                    "criterion": "women of childbearing potential",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "negative serum pregnancy test result",
                    "criterion": "serum pregnancy test result",
                    "requirements": [
                        {
                            "requirement_type": "result",
                            "expected_value": "negative"
                        }
                    ]
                },
                {
                    "exact_snippets": "within 7 days prior to initiation of Study treatment",
                    "criterion": "timing of serum pregnancy test",
                    "requirements": [
                        {
                            "requirement_type": "timing",
                            "expected_value": "within 7 days prior to initiation of Study treatment"
                        }
                    ]
                }
            ]
        },
        {
            "line": "14. Persons deprived of their liberty or under protective custody or guardianship.",
            "criterions": [
                {
                    "exact_snippets": "Persons deprived of their liberty",
                    "criterion": "deprivation of liberty",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "under protective custody",
                    "criterion": "protective custody",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "under ... guardianship",
                    "criterion": "guardianship",
                    "requirements": [
                        {
                            "requirement_type": "presence",
                            "expected_value": true
                        }
                    ]
                }
            ]
        },
        {
            "line": "15. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.",
            "criterions": [
                {
                    "exact_snippets": "unwilling or unable to comply with the medical follow-up",
                    "criterion": "compliance with medical follow-up",
                    "requirements": [
                        {
                            "requirement_type": "ability",
                            "expected_value": true
                        }
                    ]
                },
                {
                    "exact_snippets": "because of geographic, familial, social, or psychological reasons",
                    "criterion": "reasons for non-compliance",
                    "requirements": [
                        {
                            "requirement_type": "types",
                            "expected_value": [
                                "geographic",
                                "familial",
                                "social",
                                "psychological"
                            ]
                        }
                    ]
                }
            ]
        }
    ],
    "miscellaneous_lines": [],
    "failed_inclusion": [
        {
            "line": "Note: In patients with multifocal or multicentric breast cancer, the largest lesion should be measured to determine T stage and to performe the HER2DX test.",
            "criterions": [
                {
                    "exact_snippets": "multifocal or multicentric breast cancer",
                    "criterion": "breast cancer type",
                    "requirements": [
                        {
                            "requirement_type": "type",
                            "expected_value": [
                                "multifocal",
                                "multicentric"
                            ]
                        }
                    ]
                },
                {
                    "exact_snippets": "largest lesion should be measured",
                    "criterion": "lesion size",
                    "requirements": [
                        {
                            "requirement_type": "measurement",
                            "expected_value": "largest lesion"
                        }
                    ]
                },
                {
                    "exact_snippets": "determine T stage",
                    "criterion": "T stage determination",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "determine T stage"
                        }
                    ]
                },
                {
                    "exact_snippets": "perform the HER2DX test",
                    "criterion": "HER2DX test",
                    "requirements": [
                        {
                            "requirement_type": "purpose",
                            "expected_value": "perform the HER2DX test"
                        }
                    ]
                }
            ]
        }
    ],
    "failed_exclusion": [],
    "failed_miscellaneous": []
}