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10.07.2018 | Epidemiology

Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival

verfasst von: Ashirbani Saha, Michael R. Harowicz, Elizabeth Hope Cain, Allison H. Hall, Eun-Sil Shelley Hwang, Jeffrey R. Marks, Paul Kelly Marcom, Maciej A. Mazurowski

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2018

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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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Titel: Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival
verfasst von: Ashirbani Saha
Michael R. Harowicz
Elizabeth Hope Cain
Allison H. Hall
Eun-Sil Shelley Hwang
Jeffrey R. Marks
Paul Kelly Marcom
Maciej A. Mazurowski
Publikationsdatum: 10.07.2018
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 1/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4879-7

Springer Medizin

Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival