title: Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic Breast Cancer.
abstract: OBJECTIVE
  Patients with hormone receptor-negative breast cancer generally do not benefit from endocrine-targeted therapies. However, a subset with androgen receptor (AR) expression is predicted to respond to antiandrogen therapies. This phase II study explored bicalutamide in AR-positive, estrogen receptor (ER), and progesterone receptor (PgR)-negative metastatic breast cancer.
  
  
  METHODS
  Tumors from patients with ER/PgR-negative advanced breast cancer were tested centrally for AR [immunohistochemistry (IHC) > 10% nuclear staining considered positive]. If either the primary or a metastatic site was positive, patients were eligible to receive the AR antagonist bicalutamide at a dose of 150 mg daily. Clinical benefit rate (CBR), the primary endpoint, was defined as the total number of patients who show a complete response (CR), partial response (PR), or stable disease (SD) > 6 months; secondary endpoints included progression-free survival (PFS) and toxicity. Correlative studies included measurement of circulating endocrine markers and IHC surrogates for basal-like breast cancer.
  
  
  RESULTS
  Of 424 patients with ER/PgR-negative breast cancer, 12% tested AR-positive. The 6-month CBR was 19% [95% confidence interval (CI), 7%-39%] for bicalutamide. The median PFS was 12 weeks (95% CI, 11-22 weeks). Bicalutamide was well-tolerated with no grade 4/5 treatment-related adverse events observed.
  
  
  CONCLUSIONS
  AR was expressed in 12% of patients with ER/PgR-negative breast cancer screened for this trial. The CBR of 19% observed with bicalutamide shows proof of principle for the efficacy of minimally toxic androgen blockade in a select group of patients with ER/PgR-negative, AR-positive breast cancer.
authors: Authors' Affiliations: Breast Cancer Medicine Service, Departments of Pathology, Biostatistics, and Radiology, Memorial Sloan-Kettering Cancer Center; Weill Medical College of Cornell University, New York; Dana-Farber Cancer Institute; Massachusetts General Hospital, Boston, Massachusetts; Mayo Clinic, Rochester, Minnesota; Georgetown Lombardi Comprehensive Cancer Center, Washington, District of Columbia; University of North Carolina at Chapel Hill, Chapel Hill; Duke University Medical Center, Durham, North Carolina; University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, California; University of Alabama at Birmingham, Birmingham, Alabama; and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland.
authors: Ayca
authors: A
authors: Gucalp
authors: Sara
authors: S
authors: Tolaney
authors: Steven J
authors: SJ
authors: Isakoff
authors: James N
authors: JN
authors: Ingle
authors: Minetta C
authors: MC
authors: Liu
authors: Lisa A
authors: LA
authors: Carey
authors: Kimberly
authors: K
authors: Blackwell
authors: Hope
authors: H
authors: Rugo
authors: Lisle
authors: L
authors: Nabell
authors: Andres
authors: A
authors: Forero
authors: Vered
authors: V
authors: Stearns
authors: Ashley S
authors: AS
authors: Doane
authors: Michael
authors: M
authors: Danso
authors: Mary Ellen
authors: ME
authors: Moynahan
authors: Lamia F
authors: LF
authors: Momen
authors: Joseph M
authors: JM
authors: Gonzalez
authors: Arooj
authors: A
authors: Akhtar
authors: Dilip D
authors: DD
authors: Giri
authors: Sujata
authors: S
authors: Patil
authors: Kimberly N
authors: KN
authors: Feigin
authors: Clifford A
authors: CA
authors: Hudis
authors: Tiffany A
authors: TA
authors: Traina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011944:Receptors, Androgen / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D000970:Antineoplastic Agents; D006728:Hormones; D009570:Nitriles; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D014105:Tosyl Compounds; C053541:bicalutamide
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