Interim clinical trial analysis of intraoperative mass spectrometry for breast cancer surgery

Sankha S Basu,Sandro Santagata,Elizabeth C Randall,Begoña Gimenez-Cassina Lopez,Melissa A Mallory,David Calligaris,Nathalie Y R Agar,Isaiah Norton,Fake F Lu,Sylwia A Stopka,Deborah A Dillon,Walid M Abdelmoula,Michael S Regan,Mehra Golshan

doi:10.1038/s41523-021-00318-5

Abstract

Optimal resection of breast tumors requires removing cancer with a rim of normal tissue while preserving uninvolved regions of the breast. Surgical and pathological techniques that permit rapid molecular characterization of tissue could facilitate such resections. Mass spectrometry (MS) is increasingly used in the research setting to detect and classify tumors and has the potential to detect cancer at surgical margins. Here, we describe the ex vivo intraoperative clinical application of MS using a liquid micro-junction surface sample probe (LMJ-SSP) to assess breast cancer margins. In a midpoint analysis of a registered clinical trial, surgical specimens from 21 women with treatment naïve invasive breast cancer were prospectively collected and analyzed at the time of surgery with subsequent histopathological determination. Normal and tumor breast specimens from the lumpectomy resected by the surgeon were smeared onto glass slides for rapid analysis. Lipidomic profiles were acquired from these specimens using LMJ-SSP MS in negative ionization mode within the operating suite and post-surgery analysis of the data revealed five candidate ions separating tumor from healthy tissue in this limited dataset. More data is required before considering the ions as candidate markers. Here, we present an application of ambient MS within the operating room to analyze breast cancer tissue and surgical margins. Lessons learned from these initial promising studies are being used to further evaluate the five candidate biomarkers and to further refine and optimize intraoperative MS as a tool for surgical guidance in breast cancer.

Highlights

In 2019, nearly 2.4 million women were diagnosed with breast cancer worldwide; 250,000 of these women will be diagnosed in the United States[1]
We describe the application of ex vivo Mass spectrometry (MS) analysis of breast cancer tissue in the AMIGO operating suite
On average a breastconserving therapy is ~82 min at BWH, we have developed a workflow in which the research scientist is present during the whole surgery and is immersed in the surgical setting

Summary

INTRODUCTION

In 2019, nearly 2.4 million women were diagnosed with breast cancer worldwide; 250,000 of these women will be diagnosed in the United States[1]. The past two decades have brought a substantial increase in the utilization of MS-based platforms in the clinical space, including gas chromatography-MS and tandemMS for newborn metabolic screens[15,16], liquid chromatographytandem MS (LC-MS/MS) for therapeutic drug monitoring (TDM)[17], matrix-assisted laser desorption-time of flight (MALDI-TOF) for microbial identification[18], and more recently laser microdissection proteomics for characterization of amyloids[19,20] Each of these platforms allows for the reproducible measurement and identification of specific analytes, each of the methods involves extensive sample preparation and lengthy analysis time, thereby limiting their use for surgical pathology analysis, especially in the operating room where rapid feedback is desired. Among ambient ionization techniques[21], liquid microjunction surface sampling probe (LMJ-SSP) coupled with electrospray ionization[30] provides an opportunity to improve both processing

RESULTS

20 Micropapillary mucinous

DISCUSSION

METHODS