title: Metastatic breast cancer subtypes and central nervous system metastases.
abstract: BACKGROUND
  Breast cancer (BC) subtypes have different survival and response to therapy. We studied predictors of central nervous system metastases (CNS-M) and outcome after CNS-M diagnosis according to tumor subtype.
  
  
  METHODS
  488 patients with diagnosis of metastatic BC were retrospectively evaluated. According to the combination of hormone receptors (HR) and HER2 status, tumors were grouped in: Luminal (Lum), Luminal/HER2+, pure HER2-positive (pHER2+) and triple negative (TN). Time to CNS progression, CNS-M free interval and Overall Survival (OS) after CNS-M occurrence were compared by the log-rank test. Cox-proportional hazard models were used to study predictor factors associated with CNS progression, including tumor subtype and all potentially clinical relevant variables.
  
  
  RESULTS
  115 patients (pts) developed CNS-M with a median time to CNS progression of 31 months. The rate of CNS-M by subtype was: Lum 14%, Lum/HER2+ 35%, pHER2+ 49%, TN 22% (p < 0.001). Compared with Lum tumors, Lum/HER2+ (HR 2.514, p < 0.001), pHER2+ (HR 6.799, p < 0.0001) and TN (HR = 3.179, p < 0.001) subtypes were at higher risk of CNS-M. Median OS in months after CNS-M was: Lum 7.4, Lum/HER2+ 19.2, pHER2+ 7, TN 4.9 (p < 0.002). Belonging to the Lum/HER2+ subtype (HR 0.48, p < 0.037) and having isolated CNS (HR 0.37, p < 0.004) predicted significantly reduced risk of death.
  
  
  CONCLUSIONS
  After CNS-M, the Lum/HER2+ subtype appears associated with the longest OS. Prospective clinical trials would be required for evaluating the potential role of screening for asymptomatic CNS lesions and of more aggressive CNS-M treatment in Lum/HER2+ subtype.
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy; Department of Oncology, University of Torino Medical School, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Aversa
authors.affiliation: Unit of Investigative Clinical Oncology (INCO), Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy. Electronic address: valentina.rossi@ircc.it.
authors.forename: V
authors.initials: V
authors.lastname: Rossi
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy; Department of Oncology, University of Torino Medical School, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Geuna
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy; Department of Oncology, University of Torino Medical School, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Martinello
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy; Department of Oncology, University of Torino Medical School, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Milani
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Redana
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy; Department of Oncology, University of Torino Medical School, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Valabrega
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy; Department of Oncology, University of Torino Medical School, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Aglietta
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy; Department of Oncology, University of Torino Medical School, Italy; Unit of Investigative Clinical Oncology (INCO), Fondazione del Piemonte per l'Oncologia (FPO)-Candiolo Cancer Center (IRCCs), Turin, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Montemurro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor
keywords: BC subtypes; Brain metastases; Breast neoplasms; Survival outcome