title: Progression of breast cancer following locoregional ipsilateral recurrence: importance of interval time.
abstract: Studies comparing prognosis of breast cancer (BC) patients with and without locoregional recurrence (LR) present conflicting results. We aimed to improve our understanding of the impact of LR on prognosis by examining a large cohort of patients treated at Guy's and St Thomas' NHS Foundation Trust.
  
  
  
  Risk factors associated with BC-specific death were investigated using Cox proportional hazards regression in 5199 women diagnosed between 1975 and 2007. Breast cancer-specific death following LR was assessed with Poisson regression.
  
  
  
  Overall, 552 women (11%) developed LR, with a median follow-up time of 4.28 years. Known factors associated with BC-specific death (tumour stage, grade, and nodal status) were of significance in our data. Women with a shorter disease-free interval had a worse prognosis. For instance, the HR for BC-specific death among women undergoing mastectomy with an LR 0.5-1 year after diagnosis of their primary tumour was 6.67 (95% CI: 3.71-11.99), when compared with women who did not experience LR.
  
  
  
  It often remains difficult to distinguish between a genuine LR and a new primary. The HRs for risk of BC-specific death following a second lesion suggest that they may act as a marker of systemic disease, large tumour burden, or depleted host defence. The clinically highly relevant impairment in prognosis calls for further research into the underlying mechanisms. We showed that for at least 15 years of follow-up, the prognosis in women following the occurrence of an LR may benefit from careful diagnostic and therapeutic management.
authors.affiliation: King's College London, Division of Cancer Studies, Cancer Epidemiology Group, Guy's Hospital, 3rd Floor, Bermondsey Wing, London SE1 9RT, UK.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Melvin
authors.affiliation: King's College London, Division of Cancer Studies, Section of Research Oncology, London, UK.|Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Arnie D
authors.initials: AD
authors.lastname: Purushotham
authors.affiliation: King's College London, Division of Cancer Studies, Cancer Epidemiology Group, Guy's Hospital, 3rd Floor, Bermondsey Wing, London SE1 9RT, UK.|King's College London, Division of Cancer Studies, Section of Cancer Epidemiology and Population Health, London, UK.
authors.forename: Hans
authors.initials: H
authors.lastname: Garmo
authors.affiliation: King's College London, Division of Cancer Studies, Section of Research Oncology, London, UK.|Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Pinder
authors.affiliation: King's College London, Division of Cancer Studies, Section of Research Oncology, London, UK.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Fentiman
authors.affiliation: King's College London, Division of Cancer Studies, Section of Research Oncology, London, UK.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Gillett
authors.affiliation: King's College London, Division of Cancer Studies, Cancer Epidemiology Group, Guy's Hospital, 3rd Floor, Bermondsey Wing, London SE1 9RT, UK.
authors.forename: Anca
authors.initials: A
authors.lastname: Mera
authors.affiliation: King's College London, Division of Cancer Studies, Section of Cancer Epidemiology and Population Health, London, UK.
authors.forename: Margreet
authors.initials: M
authors.lastname: Lüchtenborg
authors.affiliation: King's College London, Division of Cancer Studies, Cancer Epidemiology Group, Guy's Hospital, 3rd Floor, Bermondsey Wing, London SE1 9RT, UK.|King's College London, Division of Cancer Studies, Section of Cancer Epidemiology and Population Health, London, UK.|Regional Cancer Centre, Uppsala/Örebro, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Holmberg
authors.affiliation: King's College London, Division of Cancer Studies, Cancer Epidemiology Group, Guy's Hospital, 3rd Floor, Bermondsey Wing, London SE1 9RT, UK.
authors.forename: Mieke
authors.initials: M
authors.lastname: Van Hemelrijck
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000401:mortality*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D016016:Proportional Hazards Models; D013997:Time Factors