Association between tumor mutation profile and clinical outcomes among Hispanic Latina women with triple-negative breast cancer.

Alexander Philipovskiy,Debabrata Mukherjee,Roberto Gamez,Sumit Gaur,Zeina Nahleh,Alok K Dwivedi,Renato J Aguilera,Richard Mccallum,Nandini Dey

doi:10.1371/journal.pone.0238262

Abstract

Triple-negative breast cancer (TNBC) represents 15%-20% of all breast cancer types. It is more common among African American (AA) and Hispanic-Latina (HL) women. The biology of TNBC in HL women has been poorly characterized, but some data suggest that the molecular drivers of breast cancer might differ. There are no clinical tools to aid medical oncologists with decisions regarding appropriate individualized therapy, and no way to predict long-term outcomes. The aim of this study was to characterize individual patient gene mutation profiles and to identify the relationship with clinical outcomes. We collected formalin-fixed paraffin-embedded tumors (FFPE) from women with TNBC. We analyzed the gene mutation profiles of the collected tumors and compared the results with individual patient's clinical histories and outcomes. Of 25 patients with TNBC, 24 (96%) identified as HL. Twenty-one (84%) had stage III-IV disease. The most commonly mutated genes were TP53, NOTCH1, NOTCH2, NOTCH3, AKT, MEP3K, PIK3CA, and EGFR. Compared with other international cancer databases, our study demonstrated statistically significant higher frequencies of these genes among HL women. Additionally, a worse clinical course was observed among patients whose tumors had mutations in NOTCH genes and PIK3CA. This study is the first to identify the most common genetic alterations among HL women with TNBC. Our data strongly support the notion that molecular drivers of breast cancer could differ in HL women compared with other ethnic backgrounds. Therefore, a deeper understanding of the biological mechanisms behind NOTCH gene and PIK3CA mutations may lead to a new treatment approach.

Highlights

Triple-negative breast cancer (TNBC) is characterized by a lack of steroid hormone receptor expression, such as estrogen (ER) and progesterone (PR), and by the absence or low expression of the tyrosine kinase receptor HER2
In this study we retrospectively reviewed the clinical databases of the Texas Tech Breast Care Center and the University Medical Center in El Paso, Texas, from January 2012 to December 2019 to identify all patients with a diagnosis of stage II–IV TNBC who received treatment at our institution
Thirteen patients had a tumor proportion score (TPS) of more than 1%, and six patients received combined immunotherapy with chemotherapy at some point during their treatment

Summary

Introduction

Triple-negative breast cancer (TNBC) is characterized by a lack of steroid hormone receptor expression, such as estrogen (ER) and progesterone (PR), and by the absence or low expression of the tyrosine kinase receptor HER2. TNBC is a heterogenic disease that can be subdivided into at least four distinct subtypes based on tumor gene expression profiles. These subtypes are characterized by different clinical courses and resistance to chemotherapy [2,3,4,5]. Molecular profiling is a very promising tool to predict individual tumor response to chemotherapy Such an approach has not yet been validated in prospective clinical trials

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