MYC amplification in subtypes of breast cancers in African American women

Tammey J Naab,Luisel Ricks-Santi,Massih Abawi,Ashwini K Esnakula,Jan K Blancato,Robert L Dewitty,Yasmine M Kanaan,Khepher H Makambi,Anita Gautam,Girmay Asgedom

doi:10.1186/s12885-018-4171-6

Abstract

BackgroundMYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics.MethodsWe analyzed 70 cases of well characterized archival breast ductal carcinoma specimens from AA women for MYC oncogene amplification. Utilizing immune histochemical analysis estrogen receptor (ER), progesterone receptor (PR), and (HER2/neu), were assessed. Cases were Luminal A (ER or PR+, Ki-67 < 14%), Luminal B (ER or PR+, Ki-67 = > 14% or ER or PR+ HER2+), HER2 (ER-, PR-, HER2+), and Triple Negative (ER-, PR-, HER2-) with basal-like phenotype. The relationship between MYC amplification and prognostic clinico-pathological characteristics was determined using chi square and logistic regression modeling.ResultsSixty-five (97%) of the tumors showed MYC gene amplification (MYC: CEP8 > 1). Statistically significant associations were found between MYC amplification and HER2-amplified BCa, and Luminal B subtypes of BCa (p < 0.0001), stage (p < 0.001), metastasis (p < 0.001), and positive lymph node status (p = 0.039). MYC amplification was associated with HER2 status (p = 0.01) and tumor size (p = 0.01). High MYC amplification was seen in grade III carcinomas (MYC: CEP8 = 2.42), pre-menopausal women (MYC: CEP8 = 2.49), PR-negative status (MYC: CEP8 = 2.42), and ER-positive status (MYC: CEP8 = 2.4).ConclusionsHER2 positive BCas in AA women are likely to exhibit MYC amplification. High amplification ratios suggest that MYC drives HER2 amplification, especially in HER2 positive, Luminal B, and subtypes of BCa.

Highlights

c-Myc gene (MYC) overexpression is associated with poor prognosis in breast tumors (BCa)
The objective of the study was to determine the prevalence of MYC amplification in breast cancer (BCa) tumors from African American (AA) women and determine the association between MYC amplification and BCa clinic-pathological characteristics
estrogen receptor (ER), progesterone receptor (PR), and HER2 were positive in 50%, 45.7%, and 18.6% of tumors, respectively

Summary

Introduction

MYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics. A significant racial disparity exists in the presentation and outcome of breast cancer (BCa) between African American (AA) women and non-Hispanic white women in the United States. On the basis of intrinsic gene-based signatures using transcriptional profiling, BCa has generally been subdivided into 4 major subtypes: luminal, HER2-enriched, basal-like, and normal breast tumors. TNBCs tend to be aggressive tumors with poor prognosis in part because no effective targeted therapies have been identified for this BCa subtype [7]

Objectives

Methods

Results

Conclusion