A Phase III Randomized Controlled study of Inj. Proluton (Hydroxyprogesterone caproate) as single dose preoperative therapy in patients with high risk operable breast cancer.â€

The retrospective analysis of 324 patients3 that showed that as compared to surgery performed during the follicular phase (unopposed estrogen), those who received surgery in the luteal phase (estrogenic effect opposed by progesterone) resulted in a better overall survival.  In this study, the presence of high levels of progesterone was associated with an improvement in overall survival in the lymph node positive subvgroup.

A randomized prospective trial was thus initiated in 1997 at the Tata Memorial Hospital, Mumbai, India to compare effects of primary progesterone prior to surgery versus standard care in women with early breast cancer with disease-free survival as the primary end-point.

At a median follow up of 65 months6 among 976 eligible patients, 273 recurrences and 202 deaths were recorded. In progesterone versus control groups, 5-year DFS and OS were 73.9% versus 70.2% (HR=0.87, 95%ci=0.68-1.09, p=0.23) and 80.2% versus 78.4% (HR=0.92, 95%ci=0.69-1.21, p=0.53) respectively.  In 471 node positive patients, the 5-year DFS and OS in progesterone versus control groups were 65.3%versus 54.7% (HR=0.72, 95%CI=0.54-0.97, p=0.02) and 75.7% versus 66.8% (HR=0.70, 95%CI=0.49-0.99, p=0.04) respectively. In multivariate analysis DFS was significantly improved with progesterone in node positive patients (adjusted HR=0.71, 95%CI=0.53-0.95, p=0.02) while there was no significant effect in node negative patients (interaction p=0.04 for DFS and p=0.02 for OS).

Based on the above results, and the fact that the study was carried out in a single institution, it requires to be replicated at other centres as well. It is, therefore, being proposed to carry out the study as a multicentre study in different geographical areas in women with high risk (and node positive) operable breast cancer.