Real-world impact of non-breast cancer-specific death on overall survival in resectable breast cancer

Cancer. 2017 Jul 1;123(13):2432-2443. doi: 10.1002/cncr.30617. Epub 2017 Mar 7.

Abstract

Background: The real-world occurrence rate of non-breast cancer-specific death (non-BCSD) and its impact on patients with breast cancer are poorly recognized.

Methods: Women with resectable breast cancer from 1990 to 2007 in the Surveillance, Epidemiology, and End Results database (n = 199,963) were analyzed. The outcome events of breast cancer were classified as breast cancer-specific death (BCSD), non-BCSD, or survival. Binary logistics was used to estimate the occurrence rates of non-BCSD and BCSD with different clinicopathological factors. The Gray method was used to measure the cumulative incidence of non-BCSD and BCSD. The ratio of non-BCSDs to all causes of death and stacked cumulative incidence function plots were used to present the impact of non-BCSD on overall survival (OS). Models of Cox proportional hazards regression and competing risk regression were compared to highlight the suitable model.

Results: There were 12,879 non-BCSDs (6.44%) and 28,784 BCSDs (14.39%). The oldest age group (>62 years), black race, and a single or divorced marital status were associated with more non-BCSDs. With adjustments for age, a hormone receptor-positive (HoR+) status was no longer related to increased non-BCSDs. In patients with grade 1, stage I disease and an HoR+ status as well as the oldest subgroup, a great dilution of non-BCSD on all causes of death could be observed, and this led to incorrect interpretations. The inaccuracy, caused by the commonly used Cox proportional hazards model, could be corrected by a competing risk model.

Conclusions: OS was largely impaired by non-BCSD during early breast cancer. For some future clinical trial planning, especially for the oldest patients and those with HoR+ breast cancer, non-BCSD should be considered a competing risk event. Cancer 2017;123:2432-43. © 2017 American Cancer Society.

Keywords: age; breast cancer; competing risk; hormone receptor; non-breast cancer-specific death; overall survival.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Black or African American / statistics & numerical data
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / therapy
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / mortality*
  • Carcinoma, Lobular / pathology
  • Carcinoma, Lobular / therapy
  • Cause of Death
  • Ethnicity / statistics & numerical data
  • Female
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Logistic Models
  • Marital Status
  • Mastectomy
  • Middle Aged
  • Neoplasm Staging
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Retrospective Studies
  • SEER Program
  • Survival Rate*
  • United States

Substances

  • Receptors, Estrogen
  • Receptors, Progesterone