title: Single-injection depot progesterone before surgery and survival in women with operable breast cancer: a randomized controlled trial.
abstract: OBJECTIVE
  Many nonrandomized studies have suggested better outcome for patients with breast cancer who undergo surgery during the luteal (progestogenic) phase of their menstrual cycle, but this is controversial. We investigated the effect of a single preoperative injection of hydroxyprogesterone in women with operable breast cancer (OBC) in a randomized controlled trial (ClinicalTrials.gov identifier, NCT00123669).
  
  
  METHODS
  One thousand patients with OBC were randomly assigned to receive surgery or an intramuscular injection of depot hydroxyprogesterone 500 mg 5 to 14 days before surgery. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), respectively. An analysis by axillary lymph node status was preplanned.
  
  
  RESULTS
  At a median follow-up of 65 months among 976 eligible patients, 273 recurrences and 202 deaths were recorded. In the progesterone group versus control group, 5-year DFS and OS rates were 73.9% v 70.2% (hazard ratio [HR], 0.87; 95% CI, 0.68 to 1.09; P = .23) and 80.2% v 78.4% (HR, 0.92; 95% CI, 0.69 to 1.21; P = .53), respectively. In 471 node-positive patients, the 5-year DFS and OS rates in the progesterone group versus control group were 65.3% v 54.7% (HR, 0.72; 95% CI, 0.54 to 0.97; P = .02) and 75.7% v 66.8% (HR, 0.70; 95% CI, 0.49 to 0.99; P = .04), respectively. In multivariate analysis, DFS was significantly improved with progesterone in node-positive patients (adjusted HR, 0.71; 95% CI, 0.53 to 0.95; P = .02), whereas there was no significant effect in node-negative patients (P for interaction = .04).
  
  
  CONCLUSIONS
  A single injection of hydroxyprogesterone before surgery did not improve outcomes in all women with OBC. This intervention showed significant improvement in node-positive women that may be considered hypothesis generating. If replicated in other studies, this could be a simple and inexpensive intervention, especially in developing countries where the incidence of lymph node metastasis is high.
authors.affiliation: Tata Memorial Hospital, Mumbai, India. badwera@gmail.com
authors.forename: Rajendra
authors.initials: R
authors.lastname: Badwe
authors.forename: Rohini
authors.initials: R
authors.lastname: Hawaldar
authors.forename: Vani
authors.initials: V
authors.lastname: Parmar
authors.forename: Mandar
authors.initials: M
authors.lastname: Nadkarni
authors.forename: Tanuja
authors.initials: T
authors.lastname: Shet
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Desai
authors.forename: Sudeep
authors.initials: S
authors.lastname: Gupta
authors.forename: Rakesh
authors.initials: R
authors.lastname: Jalali
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Vanmali
authors.forename: Rajesh
authors.initials: R
authors.lastname: Dikshit
authors.forename: Indraneel
authors.initials: I
authors.lastname: Mittra
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003692:Delayed-Action Preparations; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000008:administration & dosage*; D007194:India; D007273:Injections, Intramuscular; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008408:Mastectomy / Q000401:mortality*; D008597:Menstrual Cycle / Q000187:drug effects*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D018579:Patient Selection; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D003692:Delayed-Action Preparations; D006908:Hydroxyprogesterones