Gene-expression signatures to inform neoadjuvant treatment decision in HR+/HER2− breast cancer: Available evidence and clinical implications

Abstract

Over the last few years, the indication for chemotherapy use in HR+/HER2− early BC has been significantly modified by the introduction of gene-expression profiling. In the adjuvant setting, several gene-expression signatures have been validated to discriminate early stage HR+/HER2− BC with different prognosis and to identify patients for which adjuvant chemotherapy can be spared. Considering their ability to optimize the choice of adjuvant treatment and the increasing use of neoadjuvant approach in early BC, the potential use of geneexpression signatures to discriminate patients to be candidate to neoadjuvant chemotherapy or endocrine treatment appears particularly appealing. Indeed, the San Gallen Consensus Conference panel recently endorsed the use of genomic assays on core biopsies as a potential strategy for choosing the type of neoadjuvant treatment (chemotherapy or endocrine therapy) in selected patients. In this context, we here review evidence supporting the use of most common commercially available gene-expression signatures (Oncotype DX, MammaPrint, PAM50, EndoPredict and Breast Cancer Index) in patients receiving neoadjuvant therapy for HR+/HER2− BC. Data on the association of gene expression signatures and response to neoadjuvant chemotherapy or neoadjuvant endocrine therapy will be reviewed and the clinical implications of this data to guide the clinical decision-making process in early HR+/HER2− BC will be discussed.

Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC

“…Beyond this, we could utilize machine learning to derive multi-gene expression signatures that predict drug responses to specific treatments. 63 …”

“…Beyond this, we could utilize machine learning to derive multi-gene expression signatures that predict drug responses to specific treatments. 63 Resistance to therapy could be innate or acquired. 64 Multiple studies have demonstrated the importance of clonal diversity and dynamics in resistance to therapeutic agents, 65 and the use of model systems like PTCs can be extremely useful in supporting clonal expansion studies about the process of acquired resistance.…”

The Clinical Research and Latest Application of Genomic Assays in Early-Stage Breast Cancer

“… 73 , 74 Moreover, some trials have added cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) or mammalian target of rapamycin inhibitors to endocrine therapy and investigated whether 21-RS can be used as a biomarker to predict neoadjuvant efficacy. 75 The PLATO study is attempting to provide personalized neoadjuvant therapy to patients with luminal A breast cancer using the 70-gene assay in the hope of improving breast conservation rates. 76 The study is expected to be completed in 2025.…”

“…Nevertheless, the ASCO guidelines do not recommend the use of gene expression assays to guide clinical decision-making for neoadjuvant therapy. 75 , 77 Therefore, further large sample analyses are still needed.…”

Breast microbiome associations with breast tumor characteristics and neoadjuvant chemotherapy: A case-control study

“…As a common treatment of cancer, neoadjuvant chemotherapy (NAC) is usually implemented to treat patients with locally advanced BC with the aim of reducing tumor size and allowing more breast conservative therapy to be performed ( 14 ). The therapeutic effect of NAC varies significantly in term of some factors, such as expression of hormone receptors and menopausal status ( 15 , 16 ). A clinical study showed that antibiotic administration leads to a reduction in NAC efficacy and was associated with worse BC prognosis ( 17 ).…”