title: Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer.
abstract: OBJECTIVE
  Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting.
  
  
  METHODS
  To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later.
  
  
  RESULTS
  By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone.
  
  
  CONCLUSIONS
  This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results.
authors.affiliation: From the 1Millennium Wellness Center, Dayton, OH; 2Department of Surgery, Wright State University Boonshoft School of Medicine, Dayton, OH; 3First Department of Ob/Gyn, Athens University Medical School, Athens, Greece; and 4Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Glaser
authors.forename: Constantine
authors.initials: C
authors.lastname: Dimitrakakis
mesh_terms: D000369:Aged, 80 and over; D000077384:Anastrozole; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004343:Drug Implants; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human; D020360:Neoadjuvant Therapy; D009570:Nitriles / Q000008:administration & dosage; D013739:Testosterone / Q000008:administration & dosage; D014230:Triazoles / Q000008:administration & dosage; D014463:Ultrasonography
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004343:Drug Implants; D009570:Nitriles; D014230:Triazoles; D000077384:Anastrozole; D013739:Testosterone