Breast cancer-specific mortality in early breast cancer as defined by high-risk clinical and pathologic characteristics

PLoS One. 2022 Feb 25;17(2):e0264637. doi: 10.1371/journal.pone.0264637. eCollection 2022.

Abstract

Objectives: To investigate breast cancer-specific mortality by early breast cancer (EBC; Stages I-IIIC) subtype; incidence of high-risk indicators for recurrence (defined in monarchE trial); and mortality risk difference by those who did/did not meet these criteria.

Materials and methods: Analyses included patients with initial EBC diagnosis between 2010-2015 from Surveillance, Epidemiology, and End Results (SEER) data (n = 342,149). Cox proportional hazards models and Kaplan-Meier estimates examined mortality among 228,031 patients, by subtype (hormone receptor [HR]-positive [+], human epidermal growth factor receptor-2 [HER2] negative [-]; triple negative [TNBC]; HR+, HER2+; HR-, HER2+). Incidence and mortality among patients who did/did not meet monarchE clinicopathological high-risk criteria were examined.

Results: Among patients with HR+, HER2- EBC, histologic Grade 3 (vs. Grade 1) was the most influential factor on mortality (hazard ratio, 3.61; 95%CI, 3.27, 3.98). Among patients with TNBC, ≥4 ipsilateral axillary positive nodes (vs. node negative) was the most influential factor on mortality (hazard ratio, 3.46; 95%CI, 2.87, 4.17). For patients with HR-, HER2+ or HR+, HER2+ EBC, tumor size ≥5 cm (vs. <1 cm) and ≥4 ipsilateral axillary positive nodes were the most influential factors on mortality. The 60-month mortality rate for the 12% of patients within the HR+, HER2- EBC group meeting monarchE clinicopathological high-risk criteria was 16.5%, versus 7.0% (Stage II-III and node positive) and 2.8% (Stage I or node negative) for those not meeting criteria. The 60-month mortality rate for patients with TNBC was 18.5%.

Conclusion: Mortality risk and the relative importance of risk factors varied by subtype. monarchE clinicopathological high-risk criteria were associated with increased mortality risk among patients with HR+, HER2- EBC. Patients with HR+, HER2- EBC, and monarchE clinicopathological high-risk criteria experienced risk of mortality similar to patients with early TNBC. These data highlight a high unmet need in this select patient population who may benefit most from therapy escalation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology*
  • Breast Neoplasms, Male / drug therapy
  • Breast Neoplasms, Male / epidemiology
  • Breast Neoplasms, Male / mortality
  • Breast Neoplasms, Male / pathology
  • Female
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism
  • Risk Factors
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology
  • Young Adult

Substances

  • ERBB2 protein, human
  • Receptor, ErbB-2

Grants and funding

This study was funded by Eli Lilly and Company. Eli Lilly and Company contracted with Syneos Health for medical writing assistance. The funder provided support in the form of salaries for authors DRN, JB and MM, design of study, data analysis, decision to publish, and preparation of the manuscript. The funder did not have any role in data collection. The specific roles of these authors are articulated in the ‘author contributions’ section.