ShortStop-HER2: 12 Months vs. 6 Months of HER2-targeted Medications for People With HER2+ Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Trastuzumab

Inclusion Criteria:

• Patients (females and males) with clinical stage T1c-T3 (or Tx) and nodal stageN0-N1 (except T3N1 tumors, which are not eligible)

• Patients must have no residual invasive disease in the breast or lymph nodes afterthe completion of neoadjuvant therapy. Residual ductal carcinoma in situ (DCIS) isallowed. Patients with residual isolated tumor cells at surgery are considerednode-positive and are not eligible

• HER2+ by American Society of Clinical Oncology (ASCO)/College of AmericanPathologists (CAP) guidelines. Central pathology review is not required. In caseswhere there were multiple tumor sites in breast/nodes that had HER2 testing atdiagnosis, at least one site must have been HER2+ AND the treating investigator mustfeel it is in the patient's best interest to be treated as having HER2+ breastcancer

• Known hormone receptor status as defined by ASCO/CAP guidelines. Estrogen receptor (ER) and progesterone receptor (PR) of any values are allowed. Hormone receptorpositive status can be determined by either known positive ER or known positive PRstatus; hormone receptor negative status must be determined by both known negativeER and known negative PR

• If invasive disease was present in both breasts, participation in the study ispermitted as long as the eligibility criteria are met for both tumors/breasts (including the requirement that at least one biopsied site on each side must havebeen HER2+)

• Age ≥ 18 years

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Patients must have received neoadjuvant chemotherapy in combination with trastuzumabwith or without pertuzumab for a minimum of 12 weeks. All chemotherapy must havebeen completed preoperatively

• Patient must complete a minimum of 12 weeks of coverage with trastuzumab and amaximum of 24 weeks in the combined neoadjuvant and adjuvant setting prior totrial registration. Trastuzumab may have been administered either weekly oronce every 3 weeks (q3weeks). (For purposes of this eligibility criterion, asingle dose of q3week trastuzumab would provide 3 weeks of coverage; a singledose of once a week (q1week) trastuzumab would provide 1 week of coverage. If aq3week dose of trastuzumab were administered and then the subsequent dose wasdelayed for any period of time, that would still count as 3 weeks of coverage.)

• Administration of endocrine therapy for treatment of this breast cancer isallowed prior to trial registration. If a patient received prior breast cancerendocrine therapy (eg tamoxifen or aromatase inhibitor) for DCIS or preventiveindication, and endocrine therapy is indicated for treatment of their currentbreast cancer, then prior endocrine therapy must have been stopped > 12 monthsprior to registration on this protocol

• No use of investigational anti-cancer agents at time of registration

• Patient must register within 14 weeks of final surgery

• Adequate excision: Surgical removal of all clinically evident disease in the breastand lymph nodes as follows:

• Breast surgery: Total mastectomy with grossly negative margins (in the opinionof the surgeon there is no disease grossly at the margins) or breast-conservingsurgery with histologically negative margins (no ink on tumor, including DCIS)unless those margins are anterior at the skin or posterior at the chest walland no additional margin re-excision can be performed

• Lymph node surgery: Lymph node surgery must have been performed and can includesentinel lymph node biopsy, targeted axillary dissection, or axillarydissection, at the discretion of the breast surgeon

• Adequate radiation: Patients who completed breast-conserving surgery (i.e.lumpectomy) must have received or plan to receive adjuvant radiation. Ifbreast-conserving surgery was performed but patient will not be receiving breastradiation, the patient is not eligible. Patients for whom radiotherapy would berecommended for breast cancer treatment but for whom it is contraindicated becauseof medical reasons (e.g., connective tissue disorder or prior ipsilateral breastradiation) are not eligible

• Adjuvant radiation can be given on study, and in this case is encouraged to begiven concurrently with adjuvant HER2-directed therapy, per investigatordiscretion

• Targeting of the regional nodal basins will be at treating investigatordiscretion

• Not pregnant and not nursing, because this study involves agents with knownteratogenic potential. Therefore, for women of childbearing potential only, anegative serum or urine pregnancy test should be performed prior to receivingHER2-directed therapy according to local standard practice

• Adequate hepatic, renal and bone marrow function to receive adjuvant HER2-directedtherapy in the opinion of the treating investigator. There are no specific requiredlaboratory values for eligibility

• No stage IV (metastatic) breast cancer

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial

• No history of any prior (ipsilateral [ipsi-] or contralateral) invasive breastcancer. Prior DCIS is allowed

• No evidence of recurrent disease following preoperative therapy and surgery

• Patients living with HIV who are healthy and deemed by their medical team to have alow risk of AIDS-related illnesses are included in this trial. Patients withHepatitis B or Hepatitis C virus who are healthy and deemed by their medical team tomeet all other enrollment criteria are included in this trial.

• Patients with inadequate cardiac function on most recent assessment of leftventricular ejection fraction (LVEF) are not eligible for this trial. Inadequatecardiac function is defined as LVEF < 50% on echocardiogram (echo) or multiple-gatedacquisition (MUGA)

• No history of grade 3 or 4 toxicity related to trastuzumab. If pertuzumab is plannedto be given on trial, patient must also have no history of grade 3-4 toxicityrelated to pertuzumab

• No contraindication to receipt of further HER2-directed therapy

• No patients with severe, uncontrolled systemic disease that may interfere withplanned trial therapy.

Exclusion Criteria: