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

Publication ,  Journal Article
Saha, A; Harowicz, MR; Cain, EH; Hall, AH; Hwang, E-SS; Marks, JR; Marcom, PK; Mazurowski, MA
Published in: Breast Cancer Res Treat
November 2018

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.

Duke Scholars

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Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

November 2018

Volume

172

Issue

1

Start / End Page

123 / 132

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Tumor Burden
  • Retrospective Studies
  • Receptors, Estrogen
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Proportional Hazards Models
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Staging
 

Citation

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MLA
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Saha, A., Harowicz, M. R., Cain, E. H., Hall, A. H., Hwang, E.-S., Marks, J. R., … Mazurowski, M. A. (2018). Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival. Breast Cancer Res Treat, 172(1), 123–132. https://doi.org/10.1007/s10549-018-4879-7
Saha, Ashirbani, Michael R. Harowicz, Elizabeth Hope Cain, Allison H. Hall, Eun-Sil Shelley Hwang, Jeffrey R. Marks, Paul Kelly Marcom, and Maciej A. Mazurowski. “Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival.Breast Cancer Res Treat 172, no. 1 (November 2018): 123–32. https://doi.org/10.1007/s10549-018-4879-7.
Saha A, Harowicz MR, Cain EH, Hall AH, Hwang E-SS, Marks JR, et al. Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival. Breast Cancer Res Treat. 2018 Nov;172(1):123–32.
Saha, Ashirbani, et al. “Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival.Breast Cancer Res Treat, vol. 172, no. 1, Nov. 2018, pp. 123–32. Pubmed, doi:10.1007/s10549-018-4879-7.
Saha A, Harowicz MR, Cain EH, Hall AH, Hwang E-SS, Marks JR, Marcom PK, Mazurowski MA. Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival. Breast Cancer Res Treat. 2018 Nov;172(1):123–132.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

November 2018

Volume

172

Issue

1

Start / End Page

123 / 132

Location

Netherlands

Related Subject Headings

  • Young Adult
  • Tumor Burden
  • Retrospective Studies
  • Receptors, Estrogen
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Proportional Hazards Models
  • Prognosis
  • Oncology & Carcinogenesis
  • Neoplasm Staging