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Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study

  • Epidemiology
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Abstract

The objective of this study is to define the survival outcomes associated with distinct molecular phenotypes defined by immunohistochemical staining of paraffin-embedded tissues among invasive breast cancer cases identified from the Nurses’ Health Study (NHS). Tissue microarrays were constructed from archived tissue blocks of women diagnosed with breast cancer in the NHS (1976–1997). Invasive non-metastatic breast cancer tumors (n = 1,945) were classified into 1 of 5 molecular phenotypes based on immunohistochemistry assays for estrogen receptor (ER), progesterone receptor (PR), HER2, cytokeratin (CK) 5/6, epidermal growth factor receptor (EGFR) and grade. Survival outcomes were estimated using the Kaplan–Meier product limit method. Cox-proportional hazards models were fitted to determine the association of molecular phenotype with survival outcomes after adjusting for covariates. 1,279 (65.8%) tumors were classified as luminal A, 279 (14.3%) as luminal B, 95 (4.9%) as HER2 type, 203 (10.4%) as basal-like and 89 (4.6%) tumors were unclassified. The 5-year breast cancer-specific survival estimates for women with luminal A, luminal B, HER2-type, basal-like and unclassified tumors were 96, 88, 81, 89 and 85%, respectively. In the multivariable model, compared to cases with luminal A tumors, cases with luminal B (HR 1.90, 95% CI 1.33–2.71), HER2-type (HR 1.36, 95% CI 0.87–2.12), basal-like (HR 1.58, 95% CI 1.05–2.39) and unclassified (HR 1.38, 95% CI 0.87–2.20) tumors had higher hazard of breast cancer death. Similar trends were observed for both overall and recurrence-free survival. In conclusion, compared to women who have luminal A tumors those with luminal B, HER2-type, basal-like and unclassified tumors had a worse prognosis, when tumor subtype was defined by immunohistochemistry. This method may provide a cost-effective means of determining prognosis in the clinical setting.

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Abbreviations

ER:

Estrogen receptor

PR:

Progesterone receptor

HER2:

Human epidermal growth factor receptor 2

CK5/6:

Cytokeratin 5/6

EGFR:

Epidermal growth factor receptor

NHS:

Nurses’ Health Study

TMA:

Tissue microarray

OS:

Overall survival

BCS:

Breast cancer specific survival

RFS:

Recurrence-free survival

BMI:

Body mass index

HR:

Hazard ratio

95% CI:

95 percent confidence interval

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Acknowledgments

We thank Dr. Yineng Fu for central pathology review of all the breast cancer cases included in this study. We are grateful to the participants of the Nurses’ Health Study for their outstanding dedication and commitment to the study. This study was supported by GlaxoSmithKline (WE234 (EPI40307)), Public Health Service Grants CA087969, and SPORE in Breast Cancer CA089393, from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services and Breast Cancer Research Fund. Dr. Graham Colditz was supported in part by an American Cancer Society Cissy Hornung Clinical Research Professorship.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, Dubai Hospital, Dubai, UAE

    Shaheenah Dawood

  2. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Rong Hu, Michelle D. Homes & Rulla M. Tamimi

  3. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Michelle D. Homes & Rulla M. Tamimi

  4. Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Laura C. Collins, Stuart J. Schnitt & James Connolly

  5. Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA

    Graham A. Colditz

Authors
  1. Shaheenah Dawood
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  2. Rong Hu
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  3. Michelle D. Homes
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  4. Laura C. Collins
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  5. Stuart J. Schnitt
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  6. James Connolly
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  7. Graham A. Colditz
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  8. Rulla M. Tamimi
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Correspondence to Rulla M. Tamimi.

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Dawood, S., Hu, R., Homes, M.D. et al. Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study. Breast Cancer Res Treat 126, 185–192 (2011). https://doi.org/10.1007/s10549-010-1113-7

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  • DOI: https://doi.org/10.1007/s10549-010-1113-7

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