• Sepideh Saadatmand, Reini Bretveld, Sabine Siesling, and Madeleine M A Tilanus-Linthorst.
• Department of Surgery, Erasmus University Medical Centre - Cancer Institute, 3075 EA, Rotterdam, Netherlands.
• BMJ. 2015 Oct 6; 351: h4901.

ObjectivesTo assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy.DesignProspective nationwide population based study.SettingNationwide Netherlands Cancer Registry.ParticipantsFemale 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).Main Outcome MeasuresRelative survival was compared between the two cohorts. Influence of traditional prognostic factors on overall mortality was analysed with Cox regression for each cohort separately.ResultsCompared 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).ConclusionsTumour 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.© Saadatmand et al 2015.

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