(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer

Inclusion Criteria:

Premenopausal women 18 years or older
Not lactating, pregnant, or planning to become pregnant in the next year
Agree to use one non-hormonal highly effective method of contraception for the entire duration of study participation. .
ER+/HER2-: [ER] ≥ 67% or Allred Score 6-8) / HER2- (histologically confirmed) using American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
Clinical Stage IIA or IIB invasive breast cancer (per American Joint Committee on Cancer [AJCC] 8th edition clinical staging)
Nottingham Grade 1 or 2
Largest tumor diameter > 2.0 cm either by imaging or clinical examination
ECOG Performance Status (ECOG PS) of 0 to 2

Exclusion Criteria:

Inflammatory breast cancer
Prior diagnosis or treatment for breast cancer, including carcinoma in situ, or history of any other active malignancy within the past 2 years prior to study entry
Uncontrolled intercurrent illness including, but not limited to:
Ongoing or active infection requiring systemic treatment with strong inhibitors/inducers of CYP450 enzymes (including bacterial infection, fungal infection, or detectable viral infection).
Symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmias
Uncontrolled hypertension (defined as blood pressure > 160/90 mm Hg)
Uncontrolled diabetes (Hemoglobin A1c [HbA1c] >50 mmol/mol)
Marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 470 milliseconds [msec]) using Fridericia's QT correction formula seen ≤ 28 days of registration
Known cataracts or retinopathy
History of deep vein thrombosis (DVT)/pulmonary embolism (PE)
Known activated protein C (APC) resistance, an inherited coagulation disorder
Creatine clearance < 60 ml/hr by the Cockcroft-Gault equation
Total bilirubin ≥ 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) or alanine amino transferase (ALT) ≥ 2.5 x ULN
Platelet count (PLT) ≤ 75,000/mm3
Hemoglobin (Hb) ≤ 10 g/dL
Hormonal therapies including birth control and hormone replacement therapy during the study or within 1 week of registration
Allergy to endoxifen, goserelin, or exemestane or any of their components
Participation in another investigational clinical trial ≤ 6 months of registration