title: A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1).
abstract: Several expression array studies identified molecular apocrine breast cancer (BC) as a subtype that expresses androgen receptor (AR) but not estrogen receptor α. We carried out a multicentre single-arm phase II trial in women with AR-positive, estrogen, progesterone receptor and HER2-negative (triple-negative) metastatic or inoperable locally advanced BC to assess the efficacy and safety of abiraterone acetate (AA) plus prednisone.
  
  
  
  Patients with a metastatic or locally advanced, centrally reviewed, triple-negative and AR-positive (≥10% by immunohistochemistry, IHC) BC were eligible. Any number of previous lines of chemotherapy was allowed. AA (1000 mg) was administered once a day with prednisone (5 mg) twice a day until disease progression or intolerance. The primary end point was clinical benefit rate (CBR) at 6 months defined as the proportion of patients presenting a complete response (CR), partial response (PR) or stable disease (SD) ≥6 months. Secondary end points were objective response rate (ORR), progression-free survival (PFS) and safety.
  
  
  
  One hundred and forty-six patients from 27 centres consented for IHC central review. Of the 138 patients with sufficient tissue available, 53 (37.6%) were AR-positive and triple-negative, and 34 of them were included from July 2013 to December 2014. Thirty patients were eligible and evaluable for the primary end point. The 6-month CBR was 20.0% [95% confidence interval (CI) 7.7%-38.6%], including 1 CR and 5 SD ≥6 months, 5 of them still being under treatment at the time of analysis (6.4+, 9.2+, 14.5+, 17.6+, 23.4+ months). The ORR was 6.7% (95% CI 0.8%-22.1%). The median PFS was 2.8 months (95% CI 1.7%-5.4%). Fatigue, hypertension, hypokalaemia and nausea were the most common drug-related adverse events; the majority of them being grade 1 or 2.
  
  
  
  AA plus prednisone treatment is beneficial for some patients with molecular apocrine tumours and five patients are still on treatment.
  
  
  
  NCT01842321.
authors.affiliation: Department of Medical Oncology, Institut Bergonié Unicancer, Univ. Bordeaux, INSERM U916, INSERM CIC1401, Bordeaux h.bonnefoi@bordeaux.unicancer.fr.
authors.forename: H
authors.initials: H
authors.lastname: Bonnefoi
authors.affiliation: Department of Medical Oncology, Institut Bergonié Unicancer, Univ. Bordeaux, INSERM U916, INSERM CIC1401, Bordeaux.
authors.forename: T
authors.initials: T
authors.lastname: Grellety
authors.affiliation: Department of Medical Oncology, Centre Léon Bérard, Lyon.
authors.forename: O
authors.initials: O
authors.lastname: Tredan
authors.affiliation: Department of Medical Oncology, Breast Cancer Unit, Gustave Roussy, Villejuif.
authors.forename: M
authors.initials: M
authors.lastname: Saghatchian
authors.affiliation: Department of Medical Oncology, Institut Claudius Regaud, IUCT-Oncopole, Toulouse.
authors.forename: F
authors.initials: F
authors.lastname: Dalenc
authors.affiliation: Department of Breast Cancer, Centre Oscar Lambret, Lille.
authors.forename: A
authors.initials: A
authors.lastname: Mailliez
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Départemental Vendée, La Roche sur Yon.
authors.forename: T
authors.initials: T
authors.lastname: L'Haridon
authors.affiliation: Department of Medical Oncology, Institut Curie, PSL Research University, Paris.
authors.forename: P
authors.initials: P
authors.lastname: Cottu
authors.affiliation: Department of Medical Oncology, Centre Paul Papin, Angers.
authors.forename: S
authors.initials: S
authors.lastname: Abadie-Lacourtoisie
authors.affiliation: Department of Medical Oncology, Teaching Hospital, Lyon-Sud University, Lyon.
authors.forename: B
authors.initials: B
authors.lastname: You
authors.affiliation: Department of Medical Oncology, CHU Grenoble, Grenoble.
authors.forename: M
authors.initials: M
authors.lastname: Mousseau
authors.affiliation: Department of Medical Oncology, Centre Hospitalier Layné, Mont-de-Marsan.
authors.forename: J
authors.initials: J
authors.lastname: Dauba
authors.affiliation: Department of Gynecologic Surgery, Hôpital du Leman, Thonon-Les-Bains.
authors.forename: F
authors.initials: F
authors.lastname: Del Piano
authors.affiliation: Department of Medical Oncology, Centre GF Leclerc, Dijon.
authors.forename: I
authors.initials: I
authors.lastname: Desmoulins
authors.affiliation: Department of Medical Oncology, Institut Curie, St Cloud.
authors.forename: F
authors.initials: F
authors.lastname: Coussy
authors.affiliation: Department of Medical Oncology, Institut Bergonié Unicancer, Univ. Bordeaux, INSERM U916, INSERM CIC1401, Bordeaux.
authors.forename: N
authors.initials: N
authors.lastname: Madranges
authors.affiliation: Department of Medical Oncology, Institut Sainte-Catherine, Avignon.
authors.forename: J
authors.initials: J
authors.lastname: Grenier
authors.affiliation: Department of Medical Oncology, Institut Curie, PSL Research University, Paris.
authors.forename: F C
authors.initials: FC
authors.lastname: Bidard
authors.affiliation: Department of Medical Oncology, Institut Curie, PSL Research University, Paris.
authors.forename: C
authors.initials: C
authors.lastname: Proudhon
authors.affiliation: Department of Pathology, Institut Bergonié, INSERM U916, Bordeaux.
authors.forename: G
authors.initials: G
authors.lastname: MacGrogan
authors.affiliation: UNICANCER R&D, Paris.
authors.forename: C
authors.initials: C
authors.lastname: Orsini
authors.affiliation: Clinical and Epidemiological Research Unit, Institut Bergonié, INSERM CIC1401, Bordeaux.
authors.forename: M
authors.initials: M
authors.lastname: Pulido
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, Cancer Research Center of Marseille, INSERM U7258, CNRS U1068, Aix-Marseille Université, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Gonçalves
mesh_terms: D000069501:Abiraterone Acetate / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000069501:Abiraterone Acetate; D011241:Prednisone; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; C410798:AR protein, human; C508053:ERBB2 protein, human
keywords: abiraterone acetate; androgen receptor; breast cancer; molecular apocrine; triple-negative