A Single Arm Phase II Study of ADjuvant Endocrine Therapy, Pertuzumab, and Trastuzumab for Patients With Anatomic Stage I Hormone Receptor-positive, HER2-positive Breast Cancer

Exclusion Criteria

• •≤ 95 days between the date of protocol registration and the patient's most recent breast surgery for this breast cancer
• •Patients must have undergone definitive breast surgery for the current malignancy. 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.
• •Patients may have received up to 8 weeks of hormonal therapy as adjuvant treatment for this cancer. Patients should otherwise not have received prior hormonal therapy with the exception that hormonal therapy administered for less than 8-week duration at least 15 years ago is allowed.
• •Prior oophorectomy (including for cancer therapy) is allowed.
• •Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy.
• •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 in this study.
• •Men and women with any menopausal status ≥18 years of age
• •ECOG Performance Status 0 or 1
• •Participants must have normal organ and marrow function as defined below:
• •* ANC ≥ 1000/mm3
• •* hemoglobin ≥8 g/dl
• •* platelets ≥ 75,000/mm3
• •* AST and ALT both \<5x institutional ULN
• •* Total bilirubin ≤ 1.5 mg/dL. For patients with Gilbert syndrome, the direct bilirubin should be \<institutional ULN
• •* Serum creatinine ≤ 2.0 mg/dL OR calculated GFR ≥ 30mL/min
• •Left ventricular ejection fraction (LVEF) ≥ 50%
• •Post-menopausal patients must meet one of the following criteria:
• •* Prior bilateral ovariectomy/oophorectomy
• •* Age ≥ 60 years
• •* Age \< 60 years with intact uterus and amenorrhoeic for ≥ 12 consecutive months prior to chemotherapy and/or endocrine therapy exposure (medication-induced amenorrhea is not acceptable to meet this criterion)
• •* Age \< 60 years hysterectomized and FSH and plasma estradiol levels in the postmenopausal range according to local policies prior to chemotherapy and/or endocrine therapy exposure.
• •Willingness to discontinue contraceptive hormonal therapy, e.g. birth control pills, prior to registration and while on study
• •Premenopausal patients with intact uterus must have a negative serum or urine pregnancy test, including women who have had a tubal ligation and women less than 12 months from their last menstrual period.
• •Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of 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 antibody treatment and 3 months after the last dose of hormonal treatment.
• •Patients must be willing and able to sign informed consent.
• •Patients must be willing to provide archival tissue for research purposes.
• •If patient is English-speaking, must be willing to fill out patient questionnaires.
• •Neoadjuvant or adjuvant chemotherapy for this breast cancer prior to enrollment is prohibited.
• •Any of the following due to teratogenic potential of the study drugs:
• •* Pregnant women
• •* Nursing women
• •* Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, 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).
• •Participants who are receiving any other investigational agents for treatment of breast cancer, unless specific approval is obtained from the Sponsor-Investigator.
• •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.
• •Individuals with a history of a different malignancy are ineligible except for the following circumstances: