Lymph node metastases in breast cancer: investigating associations with tumor characteristics, molecular subtypes, and polygenic risk score using a continuous growth model

Gabriel Isheden* (Corresponding Author), Felix Grassmann, Kamila Czene, Keith Humphreys

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We investigate the association between rate of breast cancer lymph node spread and grade, estrogen receptor status, progesteron receptor status, decision tree derived PAM50 molecular subtype, and a polygenic risk score, using data on 10950 women included from two different data sources. Lymph node spread was analyzed using a novel continuous tumor progression model that adjusts for tumor volume in a biologically motivated way and that incorporates covariates of interest. Grade 2 and 3 tumors, respectively, were associated with 1.63 and 2.17 times faster rates of lymph node spread than grade 1 tumors (p<10-16). ER/PR negative breast cancer was associated with a 1.25/1.19 times faster spread than ER/PR positive breast cancer, respectively (p=0.0011 and p=0.0012). Among the molecular subtypes luminal A, luminal B, Her2-enriched, and basal-like, Her2-enriched breast cancer was associated with 1.53 times faster spread than luminal A cancer (p=0.00072). Polygenic risk score was not associated with the rate of lymph node spread. Continuous growth models are useful for quantifying associations between lymph node spread and tumor characteristics. These may be useful for building realistic progression models for microsimulation studies used to design individualized screening programs. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalInternational Journal of Cancer
Early online date7 Jun 2021
DOIs
Publication statusE-pub ahead of print - 7 Jun 2021

Keywords

  • Breast cancer
  • lymph node metastases
  • molecular subtype
  • polygenic risk score
  • continuous growth model

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