Modeling risks of cardiovascular and cancer mortality following a diagnosis of loco-regional breast cancer

Breast Cancer Res. 2021 Sep 27;23(1):91. doi: 10.1186/s13058-021-01469-w.

Abstract

Background: Many women with breast cancer also have a high likelihood of cardiovascular mortality, and while there are several cardiovascular risk prediction models, none have been validated in a cohort of breast cancer patients. We first compared the performance of commonly-used cardiovascular models, and then derived a new model where breast cancer and cardiovascular mortality were modeled simultaneously, to account for the competing risk endpoints and commonality of risk factors between the two events.

Methods: We included 20,462 women diagnosed with stage I-III breast cancer between 2000 and 2010 in Kaiser Permanente Northern California (KPNC) with follow-up through April 30, 2015, and examined the performance of the Framingham, CORE and SCOREOP cardiovascular risk models by area under the receiver operating characteristic curve (AUC), and observed-to -expected (O/E) ratio. We developed a multi-state model based on cause-specific hazards (CSH) to jointly model the causes of mortality.

Results: The extended models including breast cancer characteristics (grade, tumor size, nodal involvement) with CVD risk factors had better discrimination at 5-years with AUCs of 0.85 (95% CI 0.83, 0.86) for cardiovascular death and 0.80 (95% CI 0.78, 0.87) for breast cancer death compared with the existing cardiovascular models evaluated at 5 years AUCs ranging 0.71-0.78. Five-year calibration for breast and cardiovascular mortality from our multi-state model was also excellent (O/E = 1.01, 95% CI 0.91-1.11).

Conclusion: A model incorporating cardiovascular risk factors, breast cancer characteristics, and competing events, outperformed traditional models of cardiovascular disease by simultaneously estimating cancer and cardiovascular mortality risks.

Keywords: Breast cancer; Cardiovascular disease; Cardiovascular mortality; Risk prediction models.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Cohort Studies
  • Female
  • Humans
  • Middle Aged
  • Models, Statistical*
  • Risk Factors
  • Young Adult