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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

2080 - Discordance of the PAM50 intrinsic subtypes compared with IHC-based surrogate in breast cancer patients: Potential implication of genomic alterations of discordance

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Yeon Hee Park

Citation

Annals of Oncology (2018) 29 (suppl_8): viii670-viii682. 10.1093/annonc/mdy304

Authors

Y.H. Park, H.K. Kim, J.H. Cho

Author affiliations

  • Internal Medicine, Samsung Medical Center Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
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Resources

Abstract 2080

Background

In recent decades, 5 intrinsic molecular subtypes have been characterized according to variation in gene expression patterns of breast cancer. However, in real-world practice, immunohistochemistry (IHC)-based classification such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor (HER2) are routinely used. We aimed to analyze the discordance between IHC-based surrogate subtyping and PAM50 intrinsic subtypes and to assess overall survival (OS) according to discordance.

Methods

A total of 607 patients were analyzed. Hormone receptor (HR) was evaluated by IHC and HER2 by IHC and/or FISH. PAM50 intrinsic subtypes were determined according to 50 cancer genes using NanoString nCounter Analysis System. In addition, we used Ion Ampliseq Cancer Panel v2 to identify the genomic alteration related with discordance between IHC subtype and PAM50 intrinsic subtype. The Kaplan-Meier method was used for estimation of OS.

Results

The majority of patients were HR + (343/607, 56.5%) by IHC and luminal A/B (283/607, 46.6%) by PAM50. We matched concordant tumor as luminal A and HR+/HER2-, luminal B and HR+/HER2+, HR-/HER2+ and HER2-enriched, TNBC and Normal- or Basal-like. 233 patients (38.4%) were discordant between IHC-based subtypes and PAM50 intrinsic subtypes. The discordant patients were mostly HR + (176 of 234, 75.2%) and 12.4% (29 of 234) were HER2+. Using targeted sequencing with Ampliseq, we detected somatic mutation related discordant breast cancer including VHL gene in HR+/HER2- group (31% in concordant group, 0% in discordant group, P = 0.03) and IDH and RET genes (7% vs. 12%, P = 0.02, 0% vs. 25%, P = 0.02, respectively) in TNBC group. In survival analysis, among the patients with HR+, basal-like group by PAM50 showed significantly inferior OS compared with other intrinsic subtypes (p = 0.010).

Conclusions

A substantial portion of patients showed discrepancies between IHC-based subtypes and PAM50 intrinsic subtypes in our study. The survival analysis demonstrated that current IHC-based classification could misdirect treatment and result in poorer outcomes. Current guidelines of IHC for ER, PR, and HER2 would better be updated accordingly.

Clinical trial identification

Legal entity responsible for the study

Yeon Hee Park.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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