Abstract
Simple SummaryThe goal of this study was to find circulating proteins that can be easily sampled and incorporated into a clinical setting to improve predictive treatment response in HER2-positive breast cancer patients receiving neoadjuvant chemotherapy. We looked for potential biomarkers in serum, which we identified using two proteomics techniques: qualitative LC-MS/MS and a quantitative assay that assessed protein expression between responders and non-responders HER2-positive breast cancer patients to neoadjuvant chemotherapy.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.
Highlights
For an increasing number of breast cancer (BC) patients, neoadjuvant chemotherapy (NAC), or the administration of chemotherapy and other agents before surgery, is the first line of treatment [1]
We collected serum from 10 primary human epidermal growth factor receptor 2 (HER2)-positive BC cases receiving NAC at Hospital Universitario Lucus Augusti (HULA) with the experimental protocol approved by the Ethics Committee of this center
Six patients acquiring a pathologic complete response (pCR) were regarded as NAC response or “responders”, while four patients still had disease progression, defined as NAC resistance or “non-responders”, after neoadjuvant chemotherapy
Summary
For an increasing number of breast cancer (BC) patients, neoadjuvant chemotherapy (NAC), or the administration of chemotherapy and other agents before surgery, is the first line of treatment [1]. In HER2-positive breast tumors, neoadjuvant trastuzumab used in combination with standard chemotherapy can induce a 30% pCR rate [2,3,4]. With modern regimens incorporating dual anti-HER2 therapy with trastuzumab and pertuzumab, such as those used in the NeoSphere [5] and Tryphaena [6] trials, pCR rates range from 46% to 66%. This pCR rate was confirmed in the GeparSepto [7], KRISTINE [8], Symphony [9], and BERENICE [10] studies. Given the physical [11] and financial [12] costs of treatment, predictive indicators of HER2-targeted NAC response would be extremely useful in identifying patients who will benefit the most from neoadjuvant therapy and guiding the selection of the most effective techniques from the start [13]
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