An Update on Breast Cancer Multigene Prognostic Tests—Emergent Clinical Biomarkers

André Filipe Vieira,Fernando Schmitt

doi:10.3389/fmed.2018.00248

Abstract

Multigene signatures generate crucial prognostic information particularly useful for cancer patients where clinical parameters and traditional immunohistochemical markers alone lead to equivocal prognosis. Clinicians are now provided with molecular tools that assist in the outline of adjuvant therapies, namely helping decide on the extension of adjuvant endocrine therapy or on suppressing adjuvant chemotherapy in patients were toxic effects are particularly deleterious or when this treatment is fundamentally not needed. The importance of cancer multigene prognostic signatures is well elucidated in the guidelines for adjuvant systemic therapy in early-stage breast cancer and the guidelines on disease staging that are progressively integrating gene expression assays as classification biomarkers. In addition to the predictive and prognostic value, some genetic tests provide intrinsic subtyping classification. Herewith, we compare the molecular tests OncotypeDX, MammaPrint, Prosigna, EndoPredict, Breast Cancer Index, Mammostrat, and IHC4 and report the eligibility of each one in the suitable setting. Through to now, there is not a commercially available multigene test that makes recommendations regarding adjuvant treatment for HER-2 and triple negative breast cancers. Thus, these patients still receive adjuvant chemotherapy. Importantly, triple negative carcinomas are very heterogeneous regarding prognosis and new molecular signatures that decipher this very heterogeneous subgroup of breast cancer may improve the clinical management of the disease.

Highlights

The clinical course of breast cancer may be difficult to predict as this malignancy is composed of many biological subtypes that in turn exhibit intratumor heterogeneity, and patients often present at different stages of pathological development
This review focuses on seven major prognostic signatures for breast cancer (OncotypeDX, Mammaprint, Prosigna, EndoPredict, Breast Cancer Index, Mammostrat and IHC4) validated through clinical trials, some of which are already approved by Food and drug administration (FDA) and recommended by American [National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO)] and European [European Society of Medical Oncology (ESMO)] guidelines committees
Pathological and immmunohistochem istry markers remain a standard for guiding the use of treatment, the clinician may be confronted with equivocal results that require additional testing

Summary

INTRODUCTION

The clinical course of breast cancer may be difficult to predict as this malignancy is composed of many biological subtypes that in turn exhibit intratumor heterogeneity, and patients often present at different stages of pathological development. Low risk scores given by OncotypeDX, Mammaprint, Endopredict, PAM50/Prosigna, or Breast Cancer Index (BCI) can be used regardless of the tumor size, to downstage hormone receptor-positive, HER2 negative and lymph nodenegative tumors, placing them into the same prognostic category as T1a-T1b N0 M0 carcinomas As of this time, no upstaging is recommended based on multigene panel testing [22]. ASCO and NCCN make specific recommendations based on clinical studies and the level of evidence they provide on the use of genetic assays to help clinicians decide on adjuvant therapy for women with early stage invasive breast cancer (Table 1). Oncotype DX (Genomic Health, Redwood, CA) is a 21-gene signature that is one of the best-validated breast cancer multigene tests It is incorporated in the staging guidelines of AJCC 8th edition [22], as well as in ASCO therapy guidelines for early stage breast cancer treatment [23, 24], NCCN clinical practice. Candidate patients for ASCO / NCCN adjuvant chemotherapy recommendations assessment (recommended by guidelines)

A MULTIGENE SIGNATURE FOR TRIPLE NEGATIVE CARCINOMAS

Findings

CONCLUSION