title: Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients.
abstract: OBJECTIVE
  To assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy.
  
  
  METHODS
  Prospective nationwide population based study.
  
  
  METHODS
  Nationwide Netherlands Cancer Registry.
  
  
  METHODS
  Female patients with primary breast cancer diagnosed between 1999 and 2012 (n=173,797), subdivided into two time cohorts on the basis of breast cancer diagnosis: 1999-2005 (n=80,228) and 2006-12 (n=93,569).
  
  
  METHODS
  Relative survival was compared between the two cohorts. Influence of traditional prognostic factors on overall mortality was analysed with Cox regression for each cohort separately.
  
  
  RESULTS
  Compared with 1999-2005, patients from 2006-12 had smaller (≤ T1 65% (n=60,570) v 60% (n=48,031); P<0.001), more often lymph node negative (N0 68% (n=63,544) v 65% (n=52,238); P<0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60% (n=56,402) v 53% (n=42,185); P<0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-12. The relative five year survival rate in 2006-12 was 96%, improved in all tumour and nodal stages compared with 1999-2005, and 100% in tumours ≤ 1 cm. In multivariable analyses adjusted for age and tumour type, overall mortality was decreased by surgery (especially breast conserving), radiotherapy, and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-12 T1c v T1a: hazard ratio 1.54, 95% confidence interval 1.33 to 1.78), but without a significant difference in invasive breast cancers until 1 cm (2006-12 T1b v T1a: hazard ratio 1.04, 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-12 N1 v N0: 1.25, 1.17 to 1.32).
  
  
  CONCLUSIONS
  Tumour stage at diagnosis of breast cancer still influences overall survival significantly in the current era of effective systemic therapy. Diagnosis of breast cancer at an early tumour stage remains vital.
authors.affiliation: Department of Surgery, Erasmus University Medical Centre - Cancer Institute, 3075 EA, Rotterdam, Netherlands.
authors.forename: Sepideh
authors.initials: S
authors.lastname: Saadatmand
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organization, 3511 DT, Utrecht, Netherlands.
authors.forename: Reini
authors.initials: R
authors.lastname: Bretveld
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organization, 3511 DT, Utrecht, Netherlands Department of Health Technology and Services Research, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, 7500 AE, Enschede, Netherlands.
authors.forename: Sabine
authors.initials: S
authors.lastname: Siesling
authors.affiliation: Department of Surgery, Erasmus University Medical Centre - Cancer Institute, 3075 EA, Rotterdam, Netherlands m.tilanus-linthorst@erasmusmc.nl.
authors.forename: Madeleine M A
authors.initials: MM
authors.lastname: Tilanus-Linthorst
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D055088:Early Detection of Cancer; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D009426:Netherlands; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents