Mortality after breast cancer as a function of time since diagnosis by estrogen receptor status and age at diagnosis

Int J Cancer. 2019 Dec 15;145(12):3207-3217. doi: 10.1002/ijc.32214. Epub 2019 Mar 5.


Our aim was to estimate how long-term mortality following breast cancer diagnosis depends on age at diagnosis, tumor estrogen receptor (ER) status, and the time already survived. We used the population-based Australian Breast Cancer Family Study which followed-up 1,196 women enrolled during 1992-1999 when aged <60 years at diagnosis with a first primary invasive breast cancer, over-sampled for younger ages at diagnosis, for whom tumor pathology features and ER status were measured. There were 375 deaths (median follow-up = 15.7; range = 0.8-21.4, years). We estimated the mortality hazard as a function of time since diagnosis using a flexible parametric survival analysis with ER status a time-dependent covariate. For women with ER-negative tumors compared with those with ER-positive tumors, 5-year mortality was initially higher (p < 0.001), similar if they survived to 5 years (p = 0.4), and lower if they survived to 10 years (p = 0.02). The estimated mortality hazard for ER-negative disease peaked at ~3 years post-diagnosis, thereafter declined with time, and at 7 years post-diagnosis became lower than that for ER-positive disease. This pattern was more pronounced for women diagnosed at younger ages. Mortality was also associated with lymph node count (hazard ratio (HR) per 10 nodes = 2.52 [95% CI:2.11-3.01]) and tumor grade (HR per grade = 1.62 [95% CI:1.34-1.96]). The risk of death following a breast cancer diagnosis differs substantially and qualitatively with diagnosis age, ER status and time survived. For women who survive >7 years, those with ER-negative disease will on average live longer, and more so if younger at diagnosis.

Keywords: breast cancer; cohort study; estrogen receptor; mortality; survival; time-dependent effects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Australia
  • Breast / metabolism
  • Breast / pathology
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology*
  • Case-Control Studies
  • Female
  • Humans
  • Lymph Nodes / pathology
  • Middle Aged
  • Neoplasm Grading
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Estrogen / metabolism*
  • Survival Analysis


  • Receptors, Estrogen