ERB-B4 After Treatment With HDAC Inhibitor in ER+ Tamoxifen Refractory Breast Cancer

Exclusion Criteria

• •1. Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
• •2. Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
• •3. Impaired cardiac function including any one of the following:
• •* Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (\<50 beats per minute), QTcF \> 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block)
• •* Presence of atrial fibrillation (ventricular heart rate \>100 bpm)
• •* Previous history angina pectoris or acute MI within 6 months
• •* Congestive heart failure (New York Heart Association functional classification III-IV) or baseline MUGA/Echo shows LVEF \< 45%
• •4. Uncontrolled hypertension
• •5. Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1)
• •6. Concomitant use of CYP3A4 inhibitors (See Appendix 1.-2)
• •7. Patients with unresolved diarrhea ≥ grade 2
• •8. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
• •9. Other concurrent severe and/or uncontrolled medical conditions
• •10. Patients who have received chemotherapy, any investigational drug or undergone major surgery \< 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
• •11. Concomitant use of any anti-cancer therapy or radiation therapy.
• •12. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral panobinostat.
• •13. Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
• •14. Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
• •15. Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
• •16. Unable to tolerate phlebotomy
• •17. Unable to tolerate biopsy
• •18. On any other hormonal or biological treatment drugs at the time of the study