title: Clinical outcome in women with HER2-positive de novo or recurring stage IV breast cancer receiving trastuzumab-based therapy.
abstract: BACKGROUND
  Five to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation.
  
  
  METHODS
  Retrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation.
  
  
  RESULTS
  Seventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary ("de novo/surgery"). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with "recurring", "de novo/surgery" and "de novo" without surgery ("de novo/no surgery) stage IV breast cancer. However, women with "de novo/surgery" stage IV breast cancer had the longest median OS (60 months), and those with "de novo/no surgery" stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p < 0.01). Multivariate analysis confirmed these findings.
  
  
  CONCLUSIONS
  Our analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias.
authors.affiliation: Unit of Investigative Clinical Oncology (INCO), Fondazione del Piemonte per l'Oncologia, Institute for Cancer Research and Treatment (IRCCs), Candiolo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rossi
authors.affiliation: Division of Medical Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Nolè
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia, Institute for Cancer Research and Treatment (IRCCs), Candiolo, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Redana
authors.affiliation: Division of Medical Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Adamoli
authors.affiliation: Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia, Institute for Cancer Research and Treatment (IRCCs), Candiolo, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Martinello
authors.affiliation: Division of Medical Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Aurilio
authors.affiliation: Division of Medical Oncology, European Institute of Oncology, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Verri
authors.affiliation: University of Turin, Department of Biomedical Sciences and Human Oncology, Turin, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sapino
authors.affiliation: Department of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Viale
authors.affiliation: Department of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.affiliation: Unit of Investigative Clinical Oncology (INCO), Fondazione del Piemonte per l'Oncologia, Institute for Cancer Research and Treatment (IRCCs), Candiolo, Italy; Division of Medical Oncology, Fondazione del Piemonte per l'Oncologia, Institute for Cancer Research and Treatment (IRCCs), Candiolo, Italy. Electronic address: filippo.montemurro@ircc.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Montemurro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases; D012189:Retrospective Studies; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Breast cancer; De novo; HER2; Metastases; Recurring; Trastuzumab