title: Stage IV breast cancer in the era of targeted therapy: does surgery of the primary tumor matter?
abstract: BACKGROUND
  Multiple studies have suggested that resection of the primary tumor improves survival in patients with stage IV breast cancer, yet in the era of targeted therapy, the relation between surgery and tumor molecular subtype is unknown. The objective of the current study was to identify subsets of patients who may benefit from primary tumor treatment and assess the frequency of local disease progression.
  
  
  METHODS
  Patients presenting with stage IV breast cancer and intact primary tumors (n = 186) were identified from a prospectively maintained clinical database (2000-2004) and clinical data were abstracted (grading determined according to the American Joint Committee on Cancer staging system).
  
  
  RESULTS
  Surgery was performed in 69 (37%) patients: 34 (49%) patients with unknown metastatic disease at the time of surgery, 15 (22%) patients for local control, 14 (20%) patients for palliation, and in 6 (9%) patients to obtain tissue. Surgical patients were more likely to be HER-2/neu negative (P = .001), and to have smaller tumors (P = .05) and solitary metastasis (P <.001). Local therapy included axillary lymph node clearance in 33 (48%) patients and postoperative radiotherapy in 9 (13%) patients. The median survival was 35 months. Cox regression analysis identified estrogen receptor (ER) positivity (hazard ratio [HR], 0.47; 95% confidence interval [95% CI], 0.29-0.76), progesterone receptor (PR) positivity (HR, 0.57; 95% CI, 0.36-0.90), and HER-2/neu amplification (HR, 0.51; 95% CI, 0.34-0.77) as being predictive of improved survival. There was a trend toward improved survival with surgery (HR, 0.71; 95% CI, 0.47-1.06). On exploratory analyses, surgery was found to be associated with improved survival in patients with ER/PR positive or HER-2/neu-amplified disease (P = .004). No survival benefit was observed in patients with triple-negative disease.
  
  
  CONCLUSIONS
  Although a trend toward improved survival with surgery was observed, it was noted most strongly in patients with ER/PR positive and/or HER-2/neu-amplified disease. This suggests that the impact of local control is greatest in the presence of effective targeted therapy, and supports the need for further study to define patient subsets that will benefit most.
authors.affiliation: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Neuman
authors.forename: Mary
authors.initials: M
authors.lastname: Morrogh
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Van Zee
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.forename: Tari A
authors.initials: TA
authors.lastname: King
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018579:Patient Selection