Circulating Proteins Associated with Response and Resistance to Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer

Abstract

Despite the increasing use of neoadjuvant chemotherapy (NAC) in HER2-positive breast cancer (BC) patients, the clinical problem of predicting individual treatment response remains unanswered. Furthermore, the use of ineffective chemotherapeutic regimens should be avoided. Serum biomarker levels are being studied more and more for their ability to predict therapy response and aid in the development of personalized treatment regimens. This study aims to identify effective protein networks and biomarkers to predict response to NAC in HER2-positive BC patients through an exhaustive large-scale LC-MS/MS-based qualitative and quantitative proteomic profiling of serum samples from responders and non-responders. Serum samples from HER2-positive BC patients were collected before NAC and were processed by three methods (with and without nanoparticles). The qualitative analysis revealed differences in the proteomic profiles between responders and non-responders, mainly in proteins implicated in the complement and coagulation cascades and apolipoproteins. Qualitative analysis confirmed that three proteins (AFM, SERPINA1, APOD) were correlated with NAC resistance. In this study, we show that serum biomarker profiles can predict treatment response and outcome in the neoadjuvant setting. If these findings are further developed, they will be of significant clinical utility in the design of treatment regimens for individual BC patients.

Imaging‐proteomic analysis for prediction of neoadjuvant chemotherapy responses in patients with breast cancer

“…pCR to neoadjuvant chemotherapy is significantly correlated to better event‐free survival and overall survival 31 . To select potential responders to neoadjuvant chemotherapy, biomarkers that could predict patient prognosis were extensively studied 32–34 . Image features have emerged as a noninvasive tool for the prediction of patient prognosis.…”

“… 31 To select potential responders to neoadjuvant chemotherapy, biomarkers that could predict patient prognosis were extensively studied. 32 , 33 , 34 Image features have emerged as a noninvasive tool for the prediction of patient prognosis. We have developed a DLS to predict pCR to neoadjuvant chemotherapy in breast cancer, achieving a prediction accuracy of 0.923 in the validation dataset.…”

A gene expression signature in HER2+ breast cancer patients related to neoadjuvant chemotherapy resistance, overall survival, and disease-free survival

“…SERPINF2 is differentially expressed in breast cancer tissues compared with normal tissues (Malvia et al, 2019). The protein product of SERPINF2 has been found in the serum of breast cancer patients when evaluating treatment response; however, this protein appeared in both resistant and sensitive groups (Chantada-Vazquez et al, 2022).…”

Proteomics and bioinformatics analyses based on two-dimensional electrophoresis and LC-MS/MS for the primary characterization of protein changes in chicken breast meat from divergent farming systems: Organic versus antibiotic-free

“…The loading pump delivered a solution of 0.1 % formic acid in water at 10 µL/min. The micro-pump provided a flow-rate of 5 µL/min and was operated under gradient elution conditions, using 0.1 % formic acid in water as mobile phase A, and 0.1 % formic acid in acetonitrile as mobile phase B. Peptides were separated using a 90 min gradient ranging from 2 % to 90 % mobile phase B ( Anfray et al, 2021 , Peñas-Martínez et al, 2021 , Chantada-Vázquez et al, 2022 ). Data acquisition was carried out using a Data dependent workflow.…”