Ensayos clínicos

Inclusion Criteria:

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patient must have histologically confirmed HER2-positive primary invasive breast carcinoma, as defined by the 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) HER2 testing guideline focused update (Wolff et al, 2018) and determined by local testing.
• Patients hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) status must be known and will be determined by local testing. Patients with either hormone receptor-positive or hormone receptor-negative HER2-positive breast cancer are eligible.
• Patients must have clinical stage II and IIIa (T2-3/N0-2/M0) at diagnosis.
• Patients without nodal involvement (cN0) are eligible if T size ≥ 2.0 cm. 
• Patients with nodal involvement (cN1-2) are eligible if T size ≥ 1.5 cm.
• Patient must be willing and able (i.e., have no contraindication) to receive standard adjuvant therapy, consisting of HER2-directed therapy, radiation (if indicated) and endocrine therapy (if ER+) if achieving pCR at surgery.
• Patient with two separate invasive breast cancers (ipsilateral or bilateral) are eligible if both cancers are HER2-positive and at least one meets protocol eligibility (i.e., ≥ 1.5 cm if cN1-2; ≥ 2 cm if cN0) (neither tumor can be T4 or N3).
• Patients with multifocal or multicentric disease are eligible as long as all tumor foci that were tested for HER2 status at the local institution are HER2-positive, and at least one tumor focus meets eligibility criteria. 
• Patients with a history of other non-breast malignancies are eligible if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy.
• Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, and localized papillary or follicular thyroid cancer who have completed recommended treatment including surgery. Patients with any other cancers within the last 5 years are ineligible.
• Patents must have a left ventricular ejection fraction (LVEF) within normal institutional parameters (or > 50%).
• Patients must have a bilateral mammogram and diagnostic breast ultrasound (with or without breast magnetic resonance imaging [MRI]) performed at screening (within 42 days of registration).
• Baseline imaging of the ipsilateral axilla by ultrasound is mandatory. For subjects with axillary lymph node(s) suspicious on clinical exam or imaging, patient must be willing to have a needle aspiration or core biopsy to determine the presence of metastatic disease in the lymph nodes. A clip must be placed in the involved axillary lymph node.
• Women of childbearing potential and sexually active males must use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for 7 months after the last dose of study treatment.
• Patient must be willing and able to sign informed consent.
• Leukocytes ≥ 3,000/mcL (obtained ≤ 28 days prior to protocol registration).
• Absolute neutrophil count ≥ 1,500/mcL (obtained ≤ 28 days prior to protocol registration).
• Platelets ≥ 100,000/mcL (obtained ≤ 28 days prior to protocol registration).
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (obtained ≤ 28 days prior to protocol registration).
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional ULN (obtained ≤ 28 days prior to protocol registration).
• Creatinine ≤ 1.5 x institutional ULN (obtained ≤ 28 days prior to protocol registration).
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

Exclusion Criteria:

• Patient must not have a history of any prior (ipsilateral or contralateral) invasive breast cancer.
• One exception: a patient with a history of T1N0 triple negative breast cancer diagnosed more than 10 years earlier, who remains disease free is eligible.
• Patient must not have prior ipsilateral ductal breast carcinoma in situ (DCIS). Patients with prior lobular breast carcinoma in situ (LCIS), atypical hyperplasia, other high risk benign lesions or contralateral DCIS (without evidence of microinvasion) are eligible.
  • NOTE: Patients currently receiving endocrine therapy for prior contralateral DCIS are eligible.
  • Patient must not have stage IV (metastatic) breast cancer. 
• Staging studies (computed tomography [CT] chest/abdomen/pelvis and a bone scan or positron emission tomography [PET]-CT scan) are required for stage III disease or those with abnormal baseline liver function tests (LFTs), symptoms (e.g., new bone pain) or abnormal physical exam findings (National Comprehensive Cancer Network [NCCN] guidelines version [V]1.2019). 
• Patient must not have T4 and/or N3 disease, including inflammatory breast cancer.
• Patient must not have any prior treatment for the current breast cancer, including surgery, chemotherapy, hormonal therapy, radiation or experimental therapy.
• Patients must not have > grade 1 peripheral neuropathy of any etiology.
• Patient must not have a concurrent serious medical condition that would preclude completion of study therapy. For example, uncontrolled hypertension (systolic > 180 mm Hg and/or diastolic > 100 mm Hg) or clinically significant (i.e., active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to registration, unstable angina, congestive heart failure (CHF) or serious cardiac arrhythmia requiring medication and other concurrent serious diseases that may interfere with planned treatment.
• Women must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. Patients must also not expect to conceive from the time of registration, while on study treatment, and until at least 7 months after the last dose of study treatment. All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy.
• A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria:
  • has achieved menarche at some point;
  • has not undergone a hysterectomy or bilateral oophorectomy;
  • has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).