A tumor specific antibody to aid breast cancer screening in women with dense breast tissue.

Lopamudra Das Roy,Pinku Mukherjee,Laura J Moore,Joe M El-Khoury,Rahul Puri,Ru Zhou,Lloye M Dillon,Chad Livasy

doi:10.18632/genesandcancer.134

Abstract

Screening for breast cancer has predominantly been done using mammography. Unfortunately, mammograms miss 50% cancers in women with dense breast tissue. Multi-modal screenings offer the best chance of enhancing breast cancer screening effectiveness. We evaluated the use of TAB004, an antibody that recognizes the tumor form of the glycoprotein MUC1 (tMUC1), to aid early detection of breast cancer. Our experimental approach was to follow tMUC1 from the tissue into circulation. We found that 95% of human breast cancer tissues across all subtypes stained positive for TAB004. In breast cancer cell lines, we showed that the amount of tMUC1 released from tumor cells is proportional to the cell's tMUC1 expression level. Finally, we showed that TAB004 can be used to assess circulating tMUC1 levels, which when monitored in the context of cancer immunoediting, can aid earlier diagnosis of breast cancer regardless of breast tissue density. In a blinded pilot study with banked serial samples, tMUC1 levels increased significantly up to 2 years before diagnosis. Inclusion of tMUC1 monitoring as part of a multi-modal screening strategy may lead to earlier stage diagnosis of women whose cancers are missed by mammography.

Highlights

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related deaths among women worldwide [1]
We describe the specificity of TAB004 across major BC subtypes and a strategy that leverages the concept of cancer immunoediting [19, 20] and circulating the glycoprotein MUC1 (tMUC1) measurements
Given our findings that TAB004 recognized tMUC1 on 95% of BC tissue specimens and that a certain threshold of total tMUC1 in the cancer cells is needed before tMUC1 is released into circulation, we investigated in vivo imaging of tMUC1 using TAB004 to explore its potential for imaging applications

Summary

Introduction

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related deaths among women worldwide [1]. In 2016, the American Cancer Society estimated 246,660 new cases of invasive BC and about 40,450 deaths in the US. Worldwide this number is 1.7MM new cases and >500,000 deaths (http:// globocan.iarc.fr/Default.aspx). Detection of BC with regular screening increases the chances of survival. While mammograms have resulted in early diagnosis for many women, 42-50% of cancers are missed in women with dense breasts due to lesion obscuration [2,3,4,5,6,7]. Increased breast density is an independent risk factor for BC

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