ATEMPT 2.0: Adjuvant T-DM1 vs TH

• Patients must have HER2-positive Stage I histologically confirmed invasive carcinomahe breast. Patients must have node-negative (N0) or micrometastases (N1mic) breastding to the AJCC 8th edition anatomic staging table.
  • If the patient has had a negative sentinel node biopsy, then no further axillarydissection is required, and the patient is determined to be node-negative. If any dissection without sentinel lymph node biopsy is performed to determinedal status, at least six axillary lymph nodes must be removed and analyzed, anddetermined to be negative, for the patient to be considered node-negative.Axillary nodes with single cells or tumor clusters ≤ 0.2 mm by either H&E orunohistochemistry (IHC) will be considered node-negative.
  • Any axillary lymph node with tumor clusters between 0.02 and 0.2 cm is considered. Patients with a micrometastasis are eligible. An axillarydissection is not required to be performed in patients with a micrometastasisund by sentinel node evaluation. In cases where the specific pathologic size ofymph node involvement is subject to interpretation, the principal investigatorwill make the final determination as to eligibility. The investigator mustdocument approval in the patient medical record.
  • Patients who have an area of a T1aN0, ER+ (defined as >10%), HER2-negative cancerddition to their primary HER2-positive tumor are eligible.
• HER2-positive: defined as 3+ by immunohistochemistry. FISH results will not be
  considered for eligibility.

        NOTE: HER-2 status must be confirmed to be positive by central review by NeoGenomics priorg protocol therapy. Patients previously having had HER2unohistochemical testing by NeoGenomics do not need to undergo retesting for centralHER2 status.TE: DCIS components will not be counted in the determination of HER2 statusR/PR determination is required. ER and PR assays should be performed byunohistochemical methods according to the local institution standard protocol.Bilateral breast cancers that individually meet eligibility criteria are allowed.Patients with multifocal or multicentric disease are eligible, as long as each tumordividually meets eligibility criteria. Central confirmation is needed for any sitedisease that is tested to be HER2-positive by local testing (unless testing wasviously done by NeoGenomics).Patients with a history of ipsilateral DCIS are eligible if they were treated withwide excision alone, without radiation therapy. Patients with a history ofDCIS are not eligible.≤ 90 days between the planned treatment start date and the patient's most recentbreast surgery for this breast cancer≥ 18 years of age with any menopausal status.COG Performance Status 0 or 1All tumor should be removed by either a modified radical mastectomy or a segmentaly (lumpectomy), with either a sentinel node biopsy or axillary dissectionAll 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 thehology report. If all other margins are clear, a positive posterior (deep)gin is permitted, provided the surgeon documents that the excision wasd down to the pectoral fascia and all tumor has been removed. Likewise,her margins are clear, a positive anterior (superficial; abutting skin)gin is permitted provided the surgeon documents that all tumor has beenved.Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have anydications to radiation therapy. Radiation to the conserved breast is required.Patients may have received up to 4 weeks of tamoxifen therapy, or other hormonalherapy, for adjuvant therapy for this cancer. Patients cannot receive adjuvanthormonal 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 togistration are eligible. Partial breast radiation must be completed prior to 2 weeksbefore starting protocol therapy. Patients who have undergone whole breast radiationgible.Patients who have participated in a window study (treatment with an investigationalgent prior to surgery for ≤ 2 weeks) are eligible. Patients must have discontinuedhe investigational agent at least 14 days before participation.Adequate bone marrow function:ANC ≥ 1000/mm3,Hemoglobin ≥ 9 g/dlPlatelets ≥ 100,000/mm3Adequate hepatic function:Total bilirubin ≤ 1.2mg/dLAST and ALT ≤ 1.5x Institutional ULNFor patients with Gilbert syndrome, the direct bilirubin should be within theutional normal range. Serum alkaline phosphatase should be ≤ 1.5xutional ULN.Left ventricular ejection fraction (LVEF) ≥ 50%Premenopausal patients must have a negative serum or urine pregnancy test, includingwomen who have had a tubal ligation and for women less than 12 months after the onsetuse.Women of childbearing potential and men with partners of childbearing potential mustbe willing to use one highly effective form of nonhormonal contraception or twove forms of nonhormonal contraception by the patient and/or partner.Contraceptive use must be continued for the duration of the study treatment and for 7hs after the last dose of study treatment. Hormonal birth control methods are notd.Patients should have tumor tissue available, and a tissue block of sufficient size toke 15 slides, which must be sent to DFCI for correlative research. If a tissue blockunavailable, sites may send one H&E-stained slide and 15 unstained sections ofbedded tissue on uncharged slides. Slide sections should be 4-5 microns inhickness. It is also acceptable to submit 2 cores from a block of invasive tissueusing a 1.2 mm diameter coring tool. If tumor is not available, the investigator mustdocument why tissue is not available in the patient medical record, and that effortshave been made to obtain tissue.Willing and able to sign informed consentust be able to read and understand English in order to participate in the quality ofurveys. If patient does not read and understand English, the patient is stillgible, but cannot participate in the quality of life surveys.usion Criteria:Any of the following due to teratogenic potential of the study drugs:Pregnant womenursing womenWomen of childbearing potential who are unwilling to employ adequate(condoms, diaphragms, IUDs, surgical sterilization, abstinence,.).who are unwilling to employ adequate contraception (condoms, surgicalzation, abstinence, etc.).Locally advanced tumors at diagnosis, including tumors fixed to the chest wall, peaud'orange, skin ulcerations/nodules, or clinical inflammatory changes (diffuse brawnyutaneous 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 paclitaxel therapyPatients with active liver disease, for example due to hepatitis B virus, hepatitis Cvirus, autoimmune hepatic disorder, or sclerosing cholangitisdividuals with a history of a different malignancy are ineligible except for thewing circumstances:dividuals with a history of other malignancies are eligible if they have beendisease-free for at least 5 years and are deemed by the investigator to be at lowk for recurrence of that malignancy.dividuals with the following cancer are eligible regardless of when they werediagnosed and treated: cervical cancer in situ, and non-melanoma cancer of thekin.urrent illness including, but not limited to: ongoing or active, unresolvedystemic infection, renal failure requiring dialysis, active cardiac disease, prioryocardial infarction (asymptomatic changes on EKG suggestive of old MI is not anusion), history of CHF, current use of any therapy specifically for CHF,uncontrolled hypertension, significant psychiatric illness, or other conditions thathe opinion of the investigator limit compliance with study requirements.