Intra-tumor Molecular Heterogeneity in Breast Cancer: Definitions of Measures and Association with Distant Recurrence-free Survival

Overview

Journal Breast Cancer Res Treat

Specialty Oncology

Date 2018 Jul 12

PMID 29992418

Citations 5

Authors

Ashirbani Saha

Michael R Harowicz

Elizabeth Hope Cain

Allison H Hall

Eun-Sil Shelley Hwang

Jeffrey R Marks

Paul Kelly Marcom

Maciej A Mazurowski

Affiliations

Soon will be listed here.

Abstract

Purpose: The purpose of the study was to define quantitative measures of intra-tumor heterogeneity in breast cancer based on histopathology data gathered from multiple samples on individual patients and determine their association with distant recurrence-free survival (DRFS).

Methods: We collected data from 971 invasive breast cancers, from 1st January 2000 to 23rd March 2014, that underwent repeat tumor sampling at our institution. We defined and calculated 31 measures of intra-tumor heterogeneity including ER, PR, and HER2 immunohistochemistry (IHC), proliferation, EGFR IHC, grade, and histology. For each heterogeneity measure, Cox proportional hazards models were used to determine whether patients with heterogeneous disease had different distant recurrence-free survival (DRFS) than those with homogeneous disease.

Results: The presence of heterogeneity in ER percentage staining was prognostic of reduced DRFS with a hazard ratio of 4.26 (95% CI 2.22-8.18, p < 0.00002). It remained significant after controlling for the ER status itself (p < 0.00062) and for patients that had chemotherapy (p < 0.00032). Most of the heterogeneity measures did not show any association with DRFS despite the considerable sample size.

Conclusions: Intra-tumor heterogeneity of ER receptor status may be a predictor of patient DRFS. Histopathologic data from multiple tissue samples may offer a view of tumor heterogeneity and assess recurrence risk.

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