title: Disease progression pattern in metastatic breast cancer patients treated with anti-HER2 therapies.
abstract: OBJECTIVE
  Over the last decade a dramatic improvement in the treatment and prognosis of human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer (MBC) has been achieved. This study aimed to describe pattern, timing of metastases, and time to progression (TTP) of MBC patients (pts) treated with multiple lines of therapy with trastuzumab and/or lapatinib.
  
  
  METHODS
  Clinical-pathologic features, treatment-lines and metastatic sites were collected from the institutional database; TTP was evaluated for each treatment-line. A meta-analysis of treatment-line estimates was performed; Q test and I (2)-index were used to detect and estimate heterogeneity. Cox's proportional hazards model and Fine and Gray's proportional subhazards model in a competing risks setting were used to detect differences in hazard rate and to estimate relative risks.
  
  
  RESULTS
  112 pts were analyzed. The median number of treatment-lines administered was 6 (range 1-17) and 524 (86 %) disease progression events were observed (median follow up 4.2 years). Distribution of metastases at baseline remained consistent across all lines. Having a given site affected by metastasis was a major risk factor of progression in that site. Hormone-receptor-positive pts resulted more likely to progress on bone (HR = 1.88). Elderly pts were less likely to progress on CNS (HR = 0.73). Median TTP resulted superior to 5 months up to the 6th line of treatment, reaching a plateau at the 9th treatment-line.
  
  
  CONCLUSIONS
  These data suggest that risk factors for progression in HER2 positive MBC do not significantly differ between various distributions of metastases, and that MBC pts benefit from anti-HER2 therapy even in late treatment-lines.
authors.affiliation: Division of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Serpico
authors.forename: L
authors.initials: L
authors.lastname: Porcu
authors.forename: A
authors.initials: A
authors.lastname: Tessari
authors.forename: A
authors.initials: A
authors.lastname: Gevorgyan
authors.forename: G
authors.initials: G
authors.lastname: Bregni
authors.forename: G
authors.initials: G
authors.lastname: Galli
authors.forename: F
authors.initials: F
authors.lastname: de Braud
authors.forename: V
authors.initials: V
authors.lastname: Torri
authors.forename: S
authors.initials: S
authors.lastname: Di Cosimo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000556:secondary; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077341:Lapatinib; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012189:Retrospective Studies; D013997:Time Factors; D000068878:Trastuzumab / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human