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Genomic comparison of paired primary breast carcinomas and lymph node macrometastases using the Oncotype DX Breast Recurrence Score® test

  • Susan K. Boolbol
  • Manju Harshan
  • Manjeet Chadha
  • Laurie Kirstein
  • Jean-Marc Cohen
  • Paula Klein
  • Joseph Anderson
  • Deborah Davison
  • Debbie M. Jakubowski
  • Frederick L. BaehnerEmail author
  • Stephen Malamud
Preclinical study
  • 22 Downloads

Abstract

Purpose

Adjuvant therapy decisions may in part be based on results of Oncotype DX Breast Recurrence Score® (RS) testing of primary tumors. When necessary, lymph node metastases may be considered as a surrogate. Here we evaluate the concordance in gene expression between primary breast cancers and synchronous lymph node metastases, based on results from quantitative RT-PCR-based RS testing between matched primary tumors and synchronous nodal metastases.

Methods

This retrospective, exploratory study included patients (≥ 18 years old) treated at our center (2005–2009) who had ER+ , HER2-negative invasive breast cancer and synchronous nodal metastases with available tumor blocks from both sites. Paired tissue blocks underwent RS testing, and RS and single-gene results for ER, PR, and HER2 were explored between paired samples.

Results

A wide distribution of RS results in tumors and in synchronous nodal metastases were modestly correlated between 84 paired samples analyzed (Pearson correlation 0.69 [95% CI 0.55–0.78]). Overall concordance in RS group classification between samples was 63%. ER, PR, and HER2 by RT-PCR between the primary tumor and lymph node were also modestly correlated (Pearson correlation [95% CI] 0.64 [0.50–0.75], 0.64 [0.49–0.75], and 0.51 [0.33–0.65], respectively). Categorical concordance (positive or negative) was 100% for ER, 77% for PR, and 100% for HER2.

Conclusions

There is modest correlation in continuous gene expression, as measured by the RS and single-gene results for ER, PR, and HER2 between paired primary tumors and synchronous nodal metastases. RS testing for ER+ breast cancer should continue to be based on analysis of primary tumors.

Keywords

Breast cancer Genomics Lymph node Metastases Oncotype DX® Recurrence Score® 

Abbreviations

ASCO

American Society of Clinical Oncology

CI

Confidence interval

ER

Estrogen receptor

FISH

Fluorescent in situ hybridization

HER2

Human epidermal growth factor receptor 2

IHC

Immunohistochemistry

PR

Progesterone receptor

RS

Recurrence Score®

RT-PCR

Reverse transcriptase-polymerase chain reaction

transATAC

Translational study of the Arimidex, Tamoxifen, Alone or in Combination trial

Notes

Acknowledgements

The authors thank Anna Lau, PhD for editorial support.

Author contributions

SKB: made substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data; involved in drafting the manuscript or revising it critically for important intellectual content; gave final approval of the version to be published; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. MH: involved in acquisition of data and interpretation of data; gave final approval of the version to be published. MC: involved in acquisition of data; gave final approval of the version to be published. LK: involved in acquisition of data; gave final approval of the version to be published. JMC: involved in acquisition of data and interpretation of data; gave final approval of the version to be published. PK: involved in acquisition of data and interpretation of data; gave final approval of the version to be published. JA: made substantial contributions to design, acquisition of data, and interpretation of data; gave final approval of the version to be published. DD: involved in drafting the manuscript and revising it critically for important intellectual content; gave final approval of the version to be published. DMJ: made substantial contributions to data analysis and interpretation of data; involved in drafting the manuscript and revising it critically for important intellectual content; gave final approval of the version to be published. FLB: involved in revising the manuscript critically for important intellectual content; gave final approval of the version to be published. SM: made substantial contributions to conception and design, acquisition of data, and analysis and interpretation of data; involved in drafting the manuscript or revising it critically for important intellectual content; gave final approval of the version to be published.

Funding

Genomic Health provided a research grant for the analysis of the specimens and provided editorial support of manuscript development. The preparation of this study was supported in part by NIH/NCI Cancer Center Support Grant No. P30 CA008748 to Memorial Sloan Kettering Cancer Center.

Compliance with ethical standards

Conflict of interest

SKB has served on the speaker’s bureau for Genomic Health. JA was employed at Genomic Health at the time the study occurred. DD, DMJ, and FLB are currently employed at and own stock in Genomic Health. SM has served on the speaker’s bureau for and owns stock in Genomic Health. MH, MC, LK, JMC, and PK declare that they have no conflicts of interest.

Ethical approval

The study was reviewed and approved by an Institutional Review Board/Ethics Committee and appropriate Scientific Review Committees prior to initiation.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Susan K. Boolbol
    • 1
  • Manju Harshan
    • 2
  • Manjeet Chadha
    • 3
  • Laurie Kirstein
    • 4
  • Jean-Marc Cohen
    • 5
  • Paula Klein
    • 6
  • Joseph Anderson
    • 7
  • Deborah Davison
    • 7
  • Debbie M. Jakubowski
    • 7
  • Frederick L. Baehner
    • 7
    Email author
  • Stephen Malamud
    • 6
  1. 1.Department of SurgeryMount Sinai Beth IsraelNew YorkUSA
  2. 2.Department of PathologyLenox Hill HospitalNew YorkUSA
  3. 3.Department of Radiation OncologyMount Sinai Beth IsraelNew YorkUSA
  4. 4.Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkUSA
  5. 5.Department of PathologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  6. 6.Department of MedicineMount Sinai Beth IsraelNew YorkUSA
  7. 7.Genomic Health, Inc.Redwood CityUSA

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