Abstract 5460: Novel immunohistochemistry-based predictive and prognostic tests for hormone receptor-positive breast cancer
Authors: Jaksic Danira , Kaur Amandeep , Reddick Dean , Datzkiw David David , Shrivastav Shailly Varma , Gadi Vijayakrishna , Murphy Leigh , Shrivastav Anuraag 
Published: June 2023

Background: Breast cancer (BC) is the most diagnosed cancer worldwide and the most common cancer diagnosed in American women. Despite successes of adjuvant endocrine therapies in treating the most common subtype of hormone receptor-positive (HR+) BC, de novo and emergent resistance to these therapies, i.e., endocrine resistance, remains a significant concern with patients experiencing recurrences during and after adjuvant treatment. We report here unique patterns of expression (UPE) of N-myristoyltransferase 1 (NMT1) protein that are prognostic and predictive markers for HR+ BC. We have discovered that the expression and localization of NMT1 are predictive markers for the endocrine therapy response in HR+ BC. The data from many observational studies suggest that after five years of adjuvant endocrine treatment, the likelihood of distant recurrence continues for the subsequent twenty years. We have developed simple immunohistochemical (IHC)-based tests that could become part of routine first line prognostic and predictive tests and have the potential to be incorporated as necessary tests in the panel of BC tests for designing treatment regimens of BC.

Methods: Expression patterns of NMT1 were determined using IHC analyses on formalin fixed paraffin embedded primary tumor samples from treatment naïve BC patients. The tumor tissues in duplicates were stained with NMT1 monoclonal/polyclonal antibodies on an autostainer (Leica Bond). Stained slides were scored in a blinded manner to outcomes and scored with an "H" index representing the intensity and percent positive cells within each section. The relationship of UPE was correlated with clinical outcomes of RFS (RFS = endpoint recurrence and/or death due to BC) and OS (OS = endpoint death due to breast cancer).

Results: The final cohort was composed of 448 BC cases of primary HR+ tumors from patients who received adjuvant tamoxifen therapy after surgery. UPE2 (defined by &gt; median H score 100) was significantly associated with better clinical outcomes represented by both RFS (HR = 0.70, P = 0.0304, 95% CI 0.510 to 0.97, n = 440) and OS (HR = 0.71, P = 0.0306, 95% CI 0.530 to 0.97, n = 440), whereas UPE4 strongly predicted worse treatment response for both RFS (HR= 1.49, P = 0.0014, 95% CI 1.08 to 2.04, n=440) and OS (HR = 1.54, P = 0.0055, 95% CI = 1.54 to 2.08, n=440).

Conclusions: We observed that the expression and localization patterns of NMT1 constitute four unique patterns of expression signatures (UPE:1-4) and serve as prognostic and potentially predictive markers for HR+ BC. This assay provides a novel method to stratify cancers that may better enable endocrine treatment and duration optimization in the adjuvant setting for HR+ breast cancer. Moreover, in distinction to genomic assays, fewer logistic and financial barriers to implementation would exist for the UPE:1-4 IHC assay in resource-poor settings.

Citation Format: Danira Jaksic, Amandeep Kaur, Dean Reddick, David David Datzkiw, Shailly Varma Shrivastav, Vijayakrishna Gadi, Leigh Murphy, Anuraag Shrivastav. Novel immunohistochemistry-based predictive and prognostic tests for hormone receptor-positive breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5460.