Randomized Controlled Trial of Neo-adjuvant Progesterone and Vitamin D3 in Women With Large Operable Breast Cancer and Locally Advanced Breast Cancer

Randomized Controlled Trial of Neoadjuvant Progesterone and Vitamin D3 in women with Large Operable Breast Cancer and Locally Advanced Breast Cancer - A Feasibility Study Primary Progesterone Timing of surgery during the menstrual cycle and its impact on survival in premenopausal women with operable breast cancer has been extensively researched and reinvestigated by Badwe et al in the randomized clinical trial of 'Primary Progesterone Therapy for Operable Breast Cancer' at Tata Memorial Hospital. The underlying assumption was that the presence of unopposed estrogen (in follicular phase) at the time surgery may be deleterious for survival and that circulating progesterone might counteract this deleterious effect. Vitamin D3 The most prominent physiological role of hormonally active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3 or calcitriol), is regulation of calcium and phosphorous homeostasis and bone metabolism via an intracellular receptor (VDR) which is a member of steroid thyroid hormone super-family of receptors. The VDR receptors are also found in other tissues like breast and prostate. Vitamin D compounds have also been implicated in promotion of apoptosis in breast cancer cells and evidence suggests that 1,25(OH)2D3 and its synthetic analogues may potentiate responsiveness of breast cancer cells to conventional cytotoxic agents. Objectives 1. To see the effect of primary progesterone on survival in women with high risk breast cancer (large operable and locally advanced breast cancer) 2. To see the effect of Vitamin D3 as an antiproliferative, cytotoxic and apoptotic agent (negative growth regulator) by evaluation of surrogate markers of proliferation and apoptosis. Inclusion Criteria: * Unilateral breast cancer * Large operable breast cancer/LOBC (T3N0M0 or T3N1M0) and Locally advanced breast cancer/LABC (T3N1-2M0; T2N2M0) * Age \<70 years * Fit for CT Exclusion Criteria: * Prior Incision Biopsy or Excision Biopsy * Metastatic breast ca