High-doses of Vitamin D (VD) may be used as targeted therapy against breast cancer. The investigators will assess the effect of high dose VD on the following biomarkers in the breast cancer cells: VDR, estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 2 (Her2/neu), androgen receptor (AR), as well as epidermal growth factor receptor 1 (EGFR) and Ki-67, as markers of proliferation, and E-cadherin, a marker of invasion and metastasis.
This is a phase I/II open-label, non-randomized study. In phase I, a fixed weekly course of oral high-dose Vitamin D (VD) is planned for either 3, 4 or 5 weeks; patients will be sequentially enrolled into 3 groups (A, B or C respectively) in a manner such that no more than two patients may have treatment-limiting toxicities (TLTs). After the group with the optimal duration of VD therapy to achieve a "favorable response" is determined, phase II will begin enrollment. Patients must be scheduled to have surgery performed within 2- weeks of the last dose of VD.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Weekly oral dose of Vitamin D3 per protocol.
Phase 1 - Rate of Treatment-Related Toxicity in Subjects
Rate of treatment-related adverse events and other toxicities in subjects.
Time frame: From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months
Phase 2 - Rate of Favorable Treatment Response in Subjects Receiving Protocol Therapy Given Within the Optimal Duration Determined in Phase 1.
Rate of subjects achieving a "favorable treatment response" to protocol therapy given within the optimal duration determined in Phase 1. The effect of VD therapy will be assessed in terms of change in expression of VDR, ER, PR, HER2/neu, AR, Ki-67, E-cadherin and EGFR comparing surgical specimen (post-VD treatment) and baseline biopsy specimen (pre-VD treatment). The effect of VD will be described as increased expression, decreased expression or no change in expression of each marker/receptor measured. The expression of nuclear receptors/proteins (VDR, Ki-67, ER, PR, AR,) will be scored based on the percentage of positively staining nuclei as follows: * 0 (Negative) if \<1% * +1 (Weak) if \>1-10% * +2 (Moderate) if \>10-50% * +3 (Strong) if \>50% A decrease in the expression of Ki-67 by ≥+1 after treatment is considered a "favorable treatment response".
Time frame: Up to 7 Weeks
Phase 1 - Optimal Duration of Once-Weekly Protocol Therapy
The determination of the optimal duration of once-weekly protocol therapy, 3, 4 or 5 weeks, as preoperative treatment to achieve a "favorable" treatment response in subjects with the study disease. The effect of VD therapy will be assessed in terms of change in expression of VDR, ER, PR, HER2/neu, AR, Ki-67, E-cadherin and EGFR comparing surgical specimen (post-VD treatment) and baseline biopsy specimen (pre-VD treatment). The effect of VD will be described as increased expression, decreased expression or no change in expression of each marker/receptor measured. The expression of nuclear receptors/proteins (VDR, Ki-67, ER, PR, AR,) will be scored based on the percentage of positively staining nuclei as follows: * 0 (Negative) if \<1% * +1 (Weak) if \>1-10% * +2 (Moderate) if \>10-50% * +3 (Strong) if \>50% A decrease in the expression of Ki-67 by ≥+1 after treatment is considered a "favorable treatment response".
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Time frame: Up to 7 Weeks
Phase 2 - Rate of Treatment-Related Toxicity in Subjects
Rate of treatment-related adverse events and other toxicities in subjects.
Time frame: From Baseline to 30 days (+ 5 days) After Last Dose of Protocol Therapy, About 3 Months