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PAM50- and immunohistochemistry-based subtypes of breast cancer and their relationship with breast cancer mortality in a population-based study

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Abstract

Purpose

We evaluated the prognostic ability of immunohistochemistry (IHC)-based vs. PAM50-based subtypes for breast cancer mortality in a population-based study of breast cancer.

Methods

We included a total of 463 breast cancer cases from the population-based Long Island Breast Cancer Study Project (LIBCSP). IHC-based markers were abstracted from the medical records, while the PAM50-based intrinsic subtypes were assessed from tumor tissues using NanoString nCounter® Analysis System. Cox proportional hazards models were used to estimate hazards ratios (HRs) for breast cancer-specific mortality associated with subtypes.

Results

For IHC-based hormone receptor-positive (HR+) tumors (n = 361), 68.7% were classified as luminal subtypes by PAM50; for HR− tumors (n = 102), 95.1% were classified as non-luminal subtypes. Compared to HR+/HER2− subtype, HR− patients had significantly higher breast cancer mortality (HR−/HER2+: HR = 2.84, 95% CI = 1.58–5.11; triple-negative breast cancer: HR = 2.42, 95% CI = 1.44–4.06). Compared to luminal A, a higher mortality rate was observed for all other PAM50-based subtypes: luminal B (HR = 4.03, 95% CI = 1.97–8.22), HER2-enriched (HR = 6.82, 95% CI = 3.29–14.14) and basal-like (HR = 4.71, 95% CI = 2.24–9.93). Additional subtyping of HR+ patients by PAM50 provided future risk stratification where luminal B patients in this group had significant higher mortality than luminal A patients (HR = 3.93, 95% CI = 1.92–8.03). Similar results were also observed among 291 HR+/HER2− patients, but not among the HR− patients.

Conclusions

Our study suggests that for HR+ patients, especially HR+/HER2− patients, additional PAM50-based subtyping would provide better prognostic stratification and improve disease management.

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Acknowledgements

This work was supported by grant from the National Institutes of Health (NIH RO1 CA172460) and in part by grants (UO1 ES019451, UO1 CA/ES66572, and UO1 CA66572). We thank Dr. Marilie Gammon, Principal Investigator of the LIBCSP, for her work and contributions to the manuscript.

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Author notes

  1. Lin Wang and Qian Li contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, Box 1057, New York, NY, 10029 , USA

    Lin Wang, Qian Li, Vasily N. Aushev, Susan Teitelbaum & Jia Chen

  2. Department of Oncology, The Affiliated Geriatric Hospital of Nanjing Medical University, Nanjing, China

    Lin Wang

  3. Department of Medicine and Epidemiology, Columbia University, New York, USA

    Alfred I. Neugut

  4. Division of Environmental Health Sciences, Joseph L. Mailman School of Public Health, Columbia University, New York, USA

    Regina M. Santella

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  1. Lin Wang
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  2. Qian Li
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Correspondence to Jia Chen.

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Conflict of interest

Dr. Neugut has consulted for Otsuka, GlaxoSmithKline, Eisai, Hospira, and United Biosource Corp. He is a member of the Medical Advisory Board of EHE Intl. All the other authors declare that they have no conflict of interest.

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Wang, L., Li, Q., Aushev, V.N. et al. PAM50- and immunohistochemistry-based subtypes of breast cancer and their relationship with breast cancer mortality in a population-based study. Breast Cancer 28, 1235–1242 (2021). https://doi.org/10.1007/s12282-021-01261-w

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  • DOI: https://doi.org/10.1007/s12282-021-01261-w

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