Trastuzumab Emtansine or Paclitaxel and Trastuzumab in Treating Patients with Stage I HER2-Positive Breast Cancer

Inclusion Criteria

• Patients must have HER2-positive stage I histologically confirmed invasive carcinoma of the breast; patients must have node-negative (N0) or micrometastases (N1mi) breast cancer according to the American Joint Committee on Cancer (AJCC) 7th edition * If the patient has had a negative sentinel node biopsy, then no further axillary dissection is required, and the patient is determined to be node-negative; if an axillary dissection, without sentinel lymph node biopsy is performed to determine nodal status, at least 6 axillary lymph nodes must be removed and analyzed and negative for the patient to be considered node-negative; axillary nodes with single cells or tumor clusters =< 0.2 mm by either hematoxylin and eosin (H&E) or immunohistochemistry (IHC) will be considered node-negative * Any axillary lymph node with tumor clusters between 0.02 and 0.2 cm is considered a micrometastasis; patients with a micrometastasis are eligible; an axillary dissection is not required to be performed in patients with a micrometastasis found by sentinel node evaluation; in cases where the specific pathologic size of lymph node involvement is subject to interpretation, the principal investigator will make the final determination as to eligibility; the investigator must document approval in the patient medical record * Patients who have an area of a T1aN0, estrogen receptor positive (ER+), HER2 negative cancer in addition to their primary Her2 positive tumor are eligible
• ER/progesterone receptor (PR) determination is required; ER- and PR-assays should be performed by immunohistochemical methods according to the local institution standard protocol
• HER-2 positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) 2013 guidelines, confirmed by central testing (Clarient laboratories [labs]): * IHC 3+ based on circumferential membrane staining that is complete, intense OR * Fluorescence in situ hybridization (FISH) positive based on one of the three following criteria: ** Single-probe average HER2 copy number >= 6.0 signals/cell; OR ** Dual-probe HER2/chromosome 17 centromere (CEP17) ratio < 2.0 with an average HER2 copy number >= 6.0 signals/cell; OR ** Dual-probe HER2/CEP17 ratio >= 2.0 * NOTE: ductal carcinoma in situ (DCIS) components should not be counted in the determination of HER2 status * NOTE: HER-2 status must be confirmed to be positive by central review prior to patient starting protocol therapy; patients previously having had HER2 testing at Clarient Laboratories do not need to undergo retesting for central confirmation of HER2 status; a pathology report documenting testing at Clarient should be provided at time of patient registration
• Bilateral breast cancers that individually meet eligibility criteria are allowed
• Patients with multifocal or multicentric disease are eligible as long as each tumor individually meets eligibility criteria; central confirmation is needed for any site of disease that is tested to be HER2-positive by local testing (unless testing was done by Clarient)
• Patients with a history of ipsilateral DCIS are eligible if they were treated with wide-excision alone, without radiation therapy; patients with a history of contralateral DCIS are not eligible
• Patients should have tumor tissue available, and a tissue block of sufficient size to make 15 slides, which must be sent to Dana-Farber Cancer Institute (DFCI) for correlative research; if a tissue block is unavailable, sites may send one H&E stained slide and 15 unstained sections of paraffin-embedded tissue on uncharged slides; slide sections should be 4-5 microns in thickness; it is also acceptable to submit 2 cores from a block of invasive tissue using a 1.2 mm diameter coring tool; if tumor is not available, the investigator must document why tissue is not available in the patient medical record, and that efforts have been made to obtain tissue
• =< 90 days between the planned treatment start date and the patient’s most recent breast surgery for this breast cancer
• All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy), with either a sentinel node biopsy or axillary dissection * All margins should be clear of invasive cancer or DCIS (i.e. no tumor on ink); the local pathologist must document negative margins of resection in the pathology report; if all other margins are clear, a positive posterior (deep) margin is permitted, provided the surgeon documents that the excision was performed down to the pectoral fascia and all tumor has been removed; likewise, if all other margins are clear, a positive anterior (superficial; abutting skin) margin is permitted provided the surgeon documents that all tumor has been removed; radiation therapy to the conserved breast is required
• Endocrine therapy * May have received up to 4 weeks of tamoxifen therapy, or other hormonal therapy, for adjuvant therapy for this cancer; patients cannot receive adjuvant hormonal therapy during protocol treatment for the first 12 weeks
• Prior oophorectomy for cancer prevention is allowed
• Patients who have undergone partial breast radiation (duration =< 7 days) prior to registration are eligible; partial breast radiation must be completed prior to 2 weeks before starting protocol therapy; patients who have undergone whole breast radiation are not eligible
• Patients who have participated in a window study (treatment with an investigational agent prior to surgery for =< 2 weeks) are eligible; patients must have discontinued the investigational agent at least 14 days before participation
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Hemoglobin >= 9 g/dL
• Platelets >= 100,000/mm^3
• Total bilirubin =< 1.2 mg/dL; for patients with Gilbert syndrome, the direct bilirubin should be within the institutional normal range
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 1.5 x institutional upper limit of normal (ULN)
• Serum alkaline phosphatase should be =< 1.5 x institutional ULN
• Patients who have not been tested within 3 months prior to starting adjuvant therapy must be tested for hepatitis B and hepatitis C serologies during study screening * Patients with positive hepatitis B or C serologies without known active disease must meet the eligibility requirements for ALT, AST, total bilirubin, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and alkaline phosphatase on at least two consecutive occasions, separated by at least 1 week, within the 30 day screening period
• Left ventricular ejection fraction (LVEF) >= 50%
• Willingness to discontinue sex hormonal therapy, e.g. birth control pills, prior to registration and while on study
• Premenopausal patients must have a negative serum or urine pregnancy test, including women who have had a tubal ligation and for women less than 12 months after the onset of menopause
• Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form on nonhormonal contraception or two effective forms of nonhormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 7 months after the last dose of study treatment
• Potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors, such as ketoconazole and erythromycin, should be avoided during the study treatment period with trastuzumab emtansine
• Excessive alcohol intake (more than 3 alcoholic beverages per day) should be avoided (occasional use is permitted)
• Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy
• Willing and able to sign informed consent
• Willing to provide tissue for research purposes
• Must be able to read and understand English in order to participate in the quality of life surveys; if patient does not read and understand English, the patient is still eligible, but cannot participate in the quality of life surveys

Exclusion Criteria

• Any of the following: * Pregnant women * Nursing women * Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, intrauterine devices [IUDS], surgical sterilization, abstinence, etc); hormonal birth control methods are not permitted * Men who are unwilling to employ adequate contraception (condoms, surgical sterilization, abstinence, etc)
• Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peau d’orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawny cutaneous induration with an erysipeloid edge)
• Patients with a history of previous invasive breast cancer
• History of prior chemotherapy in the past 5 years
• History of prior paclitaxel therapy
• Active, unresolved infection
• Patients with active liver disease, for example, due to hepatitis B virus, hepatitis C virus, autoimmune hepatic disorder, or sclerosing cholangitis
• Individuals with a history of a different malignancy are ineligible except for the following circumstances; individuals with a history of other 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; in addition, individuals with the following cancer are eligible regardless of when they were diagnosed and treated: cervical cancer in situ, basal cell or squamous cell carcinoma of the skin
• Active cardiac disease * Any prior myocardial infarction (asymptomatic changes on electrocardiogram [EKG] suggestive of old myocardial infarction [MI] is not an exclusion) * Documented congestive heart failure (CHF) * Current use of any therapy specifically for CHF * Current uncontrolled hypertension (diastolic > 100 mmHg or systolic > 200 mmHg) * Clinically significant pericardial effusion
• Significant intercurrent illness including, but not limited to ongoing or active systemic infection, renal failure requiring dialysis, active cardiac disease, psychiatric illness/social situations, or other conditions that in the opinion of the investigator limit compliance with study requirements