title: Prognostic factors of brain metastases from breast cancer: impact of targeted therapies.
abstract: BACKGROUND
  Brain metastases (BM) from breast cancer are associated with poor prognosis. This study was made to determine the prognostic influence of breast cancer biological subtypes, and to define the best therapeutic options in this setting, with a special focus on the HER2-positive population.
  
  
  METHODS
  Breast cancer patients with known hormone receptors (HR) and HER2 status presenting with BM treated between 1995 and 2010 in our two institutions were considered for this retrospective study.
  
  
  RESULTS
  250 patients were included. The study population consisted of 25.6% patients categorized as triple-negative (HR-/HER2-), 30.8% as HR+/HER2- and 43.6% as HER2+ breast cancer. Median overall survival (OS) was 8.9 months (95% CI, 6.9-10.3 months). Cerebral progression remained the most frequent cause of death (57.1%). On multivariate analysis, HER2 positivity and the RPA score were the two most important prognostic factors. Local treatment (surgery or stereotactic radiotherapy) and chemotherapy were significantly associated with an increased survival. On multivariate analysis of the RPA1-2 population, local treatment and chemotherapy were independent prognostic factors in addition to biological subtypes, RPA class, liver metastases and clinical signs of intra-cranial hypertension. Anti-HER2 therapies administered after BM diagnosis significantly and independently increased OS. Median OS in patients receiving both trastuzumab and lapatinib after BM diagnosis was significantly better than that the one of patients receiving only one of the 2 targeted therapies (25.7 vs. 9.6 months, p < 0.001).
  
  
  CONCLUSIONS
  Biological subtypes are independent prognostic determinants. Chemotherapy and targeted therapies positively affect the prognosis after first BM.
authors.affiliation: Department of Radiation Oncology, Val d'Aurelle Cancer Institute, 208 rue des Apothicaires, 34298 Montpellier, France. Electronic address: antoine.braccini@montpellier.unicancer.fr.
authors.forename: Antoine Laurent
authors.initials: AL
authors.lastname: Braccini
authors.forename: David
authors.initials: D
authors.lastname: Azria
authors.forename: Simon
authors.initials: S
authors.lastname: Thezenas
authors.forename: Gilles
authors.initials: G
authors.lastname: Romieu
authors.forename: Jean Marc
authors.initials: JM
authors.lastname: Ferrero
authors.forename: William
authors.initials: W
authors.lastname: Jacot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000737:chemistry / Q000556:secondary / Q000628:therapy*; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000556:secondary / Q000628:therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019586:Intracranial Hypertension / Q000209:etiology; D053208:Kaplan-Meier Estimate; D000077341:Lapatinib; D008113:Liver Neoplasms / Q000556:secondary*; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D011799:Quinazolines / Q000627:therapeutic use*; D016634:Radiosurgery; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D015996:Survival Rate; D000068878:Trastuzumab; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Brain metastases; Breast cancer; HER2; Prognostic factors; Targeted therapies