Inclusion criteria:

          1. Subjects must have a histologically confirmed diagnosis of HR+/HER2+ locally advanced
             unresectable or metastatic breast cancer. Estrogen or progesterone receptor positivity
             is defined by IHC according to the most recent ASCO/CAP guidelines [29]. HER2
             positivity is defined by standard of care fluorescence in situ hybridization (FISH)
             and/or 3+ staining by IHC according to the most recent ASCO/CAP guidelines [30].

          2. Measurable and/or evaluable disease per RECIST 1.1 criteria and/or RANO-BM criteria
             (Appendix C). Bone only disease is allowed.

          3. CNS inclusion criteria:

               -  Subjects without CNS metastases are eligible. Note: brain imaging is not required
                  for asymptomatic subjects without known brain metastatic disease prior to
                  enrollment into the study

               -  Subjects with untreated asymptomatic CNS metastases not needing immediate local
                  therapy in the opinion of investigator are eligible. For subjects with untreated
                  asymptomatic CNS lesions > 2.0 cm by contrast-enhanced MRI, discussion with and
                  approval from the Lead PI is required prior to enrollment

               -  Subjects with stable brain metastases previously treated with radiation therapy
                  or surgery are allowed to enroll, provided that they are off corticosteroids or
                  on stable/tapering dose of corticosteroids and stability of CNS metastatic
                  disease for at least 4 weeks has been demonstrated, with the last MRI taken
                  within 2 weeks prior to cycle 1 day 1 of the study. Relevant records of any CNS
                  treatment must be available to allow for classification of target and non-target
                  lesions

          4. Age ≥ 18 years

          5. ECOG performance status 0-1

          6. Life expectancy of more than 6 months, in the opinion of the investigator

          7. Study subjects should be post-menopausal women; premenopausal women are eligible if on
             ovarian suppression, or agreeable to mandatory ovarian suppression. Women of
             childbearing potential, defined as premenopausal women who are not permanently sterile
             (i.e., due to hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or
             bilateral tubal occlusion) are required to have negative pregnancy tests prior to
             initiation of treatment.

          8. Prior treatments:

               -  Subjects should have received at least two approved HER2-targeted agents
                  (trastuzumab, pertuzumab, or TDM-1) in the course of their disease

               -  Subjects should have had at least 1 line of prior HER2-targeted therapy in the
                  metastatic setting, with the exception of asymptomatic subjects with
                  oligometastatic or bone / soft tissue only disease who, on investigator opinion,
                  are appropriate for a single agent anti-endocrine therapy per NCCN guidelines

               -  Subjects who have had up to 2 lines of prior endocrine therapy in the metastatic
                  setting are allowed. Prior adjuvant and/or neoadjuvant endocrine regimens are
                  allowed and not counted towards this limit

          9. Adequate organ and marrow function as defined below:

               -  Absolute neutrophil count ≥ 1,500/mm3

               -  Platelets ≥ 75,000/mm3

               -  Hemoglobin ≥ 9.0 mg/dL without red blood cell transfusion ≤ 7 days prior to Cycle
                  1 Day 1 of therapy

               -  Total serum bilirubin ≤ 1.5 X upper limit of normal (ULN) except for subjects
                  with known Gilbert's disease, who may enroll if the conjugated bilirubin is ≤ 1.5
                  ULN

               -  AST (SGOT)/ALT (SGPT) ≤2.5 X ULN;

               -  Serum creatinine ≤ 1.5 mg/dL

               -  International normalized ratio (INR) and activated partial thromboplastin time
                  (aPTT) ≤ 1.5 X ULN unless on medication known to alter INR and aPTT

               -  Left ventricular ejection fraction (LVEF) ≥ 50% (as assessed by ECHO or MUGA)
                  documented within 4 weeks prior to first dose of study treatment

               -  Serum or urine pregnancy test (for women of childbearing potential) negative ≤ 7
                  days of starting treatment

         10. Ability to understand and the willingness to sign a written informed consent and
             comply with the study scheduled visits, treatment plans, laboratory tests and other
             procedures.

         11. Subject or legally authorized representative of a subject must provide signed informed
             consent per a consent document that has been approved by an institutional review board
             or independent ethics committee (IRB/IEC) prior to initiation of any study-related
             tests or procedures that are not part of standard-of-care for the subject's disease.

        Exclusion criteria:

          1. Subjects with previously treated progressing brain metastases are excluded from the
             study

          2. Subjects with known brain metastases and contraindications to undergo contrast MRI
             imaging of the brain are excluded from the study

          3. Pregnancy or breast feeding

          4. Current active treatment with an investigational agent

          5. Known history of hypersensitivity to aromatase-inhibitor drugs

          6. Any toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1,
             with the exception of peripheral neuropathy, which must have resolved to ≤ Grade 2,
             and alopecia

          7. Previous treatment with lapatinib, neratinib, afatinib, or other investigational
             EGFR-family receptor tyrosine kinase inhibitor or HER2 tyrosine kinase inhibitor

          8. Previous treatment with palbociclib, abemaciclib, ribociclib or other investigational
             CDK4/6 inhibitors

          9. Any systemic anti-cancer therapy (including hormonal therapy), radiation, or
             experimental agent ≤ 2 weeks of first dose of study treatment

         10. Active bacterial, fungal or viral infections requiring treatment with IV antibiotic,
             IV anti-fungal, or IV anti-viral drugs

         11. Known hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV)
             infections. Note: pretesting is not required.

         12. Inability to swallow pills or any significant gastrointestinal disease which would
             preclude the adequate oral absorption of medications

         13. Use of prohibited medications listed in Appendix D within 3 elimination half-lives
             prior to first dose of the study treatment

         14. Known myocardial infarction, severe/unstable angina, percutaneous transluminal
             coronary angioplasty/stenting (PTCA), or coronary artery bypass graft (CABG) within 6
             month of the first dose of the study treatment

         15. Clinically significant cardio-vascular disease, such as ventricular arrhythmia
             requiring therapy, uncontrolled hypertension (defined as persistent systolic blood
             pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive
             medications), or any history of symptomatic congestive heart failure (CHF)

         16. Other severe acute or chronic medical or psychiatric conditions or laboratory
             abnormalities that may increase the risk associated with study participation or study
             drug administration, or may interfere with the interpretation of study results, or in
             the judgment of the investigator would make the subject inappropriate for entry into
             the study.