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

Abstract

We investigate the association between rate of breast cancer lymph node spread and grade, estrogen receptor (ER) status, progesteron receptor status, decision tree derived PAM50 molecular subtype and a polygenic risk score (PRS), using data on 10 950 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. Grades 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 À16 ). ER/PR negative breast cancer was associated with a 1.25/1.19 times faster spread than ER/PR positive breast cancer, respectively (P = .0011 and .0012). Among the molecular subtypes luminal A, luminal B, Her2-enriched and basallike, Her2-enriched breast cancer was associated with 1.53 times faster spread than luminal A cancer (P = .00072). PRS 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. K E Y W O R D Sbreast cancer, continuous growth model, lymph node metastases, molecular subtype, polygenic risk score What's new?Breast cancer aggressiveness is reflected in the tumour's propensity to spread to the lymph nodes, in many cases a precursory step of distant metastatic spread. Here, the authors apply a novel continuous tumour progression model to estimate the rate of lymph node spread during the tumour's preclinical phase based on grade, oestrogen receptor status, progesterone receptor status, molecular subtype, and polygenic risk score. Combining two datasets with a total of 10,950 women with invasive breast cancer, they show that quantifying tumour aggressiveness using continuous growth models may prove useful in the future era of individualised screening and treatment.

Estimation of age of onset and progression of breast cancer by absolute risk dependent on polygenic risk score and other risk factors

“…Cardozo et al 25 and Li et al 26 found that interval cancers were associated with lower PRS. Our results show agreement with Ishden et al 24 and Cardozo et al 25 because our results show little difference in the sojourn time between low risk and high risk based on PRS. Lower-risk cancers had shorter sojourn time than higher-risk cancers, although this difference was not significant.…”

“…However, the finding that sojourn time does not vary substantially by risk group, that is, higher risk is not associated with faster progression or more aggressive disease, is aligned with other studies. Taghipour et al 23 Isheden et al 24 found no association between the rate of lymph node spread, a measure of tumor aggressiveness, and PRS. Cardozo et al 25 and Li et al 26 found that interval cancers were associated with lower PRS.…”

A natural history and copula-based joint model for regional and distant breast cancer metastasis

“…The data on distant metastases has been used before to study the association of mammographic density and the risk of distant spread 22 ; the (marginal) natural history model of lymph node spread was also developed using CAHRES (and other) data. 14 , 23 , 24 Mammographic images and screening histories were collected from mammography screening units and radiology departments, in an extension of the original case-control study; the collection of this data has also been described previously. 25 , 26 CAHRES is an old study, which for us has several advantages: first, there is an adequate follow-up to study breast cancer spread to distant metastasis.…”

A Nomogram for Predicting Liver Metastasis of Lymph-Node Positive Luminal B HER2 Negative Subtype Breast Cancer by Analyzing the Clinicopathological Characteristics of Patients with Breast Cancer

“…A vast number of molecular subtypes of BC exist with Luminal B-like human epidermal growth factor receptor 2 negative (Luminal B [HER2−]), which accounts for more than half the cases of BC, 5 has a longer recurrence-free and metastasis-free survival rate. 6 Owing to the heterogeneity in their clinical behavior, 7 , 8 development of a special population occurs as patients evolve from BC to LM; thus, special clinicopathological characteristics can be seen within this special internal environment. 9 , 10 …”

“…A vast number of molecular subtypes of BC exist with Luminal B-like human epidermal growth factor receptor 2 negative (Luminal B [HER2−]), which accounts for more than half the cases of BC, 5 has a longer recurrence-free and metastasis-free survival rate. 6 Owing to the heterogeneity in their clinical behavior, 7,8 development of a special population occurs as patients evolve from BC to LM; thus, special clinicopathological characteristics can be seen within this special internal environment. 9,10 The clinical features of the relationship between BC and LM are poorly defined; thus, defining the high-risk clinicopathological characteristics for individuals and determining the possible treatment options may provide a reference for the inclusion criteria of new clinical trials directed toward patients with high risk of LM.…”