Journal Article

Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism

Levine, Kevin M., Tseng, George C., Houten, Bennett Van, Vignali, Dario A. A., Zhu, Li, Tasdemir, Nilgun, Oesterreich, Steffi, Du, Tian, Lee, Adrian V.

2018

Overview

Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set. Top pathways that were significantly enriched in ILC were related to immune response. ILC exhibited a higher activity of almost all types of immune cells based on cell type-specific signatures compared to IDC. Conversely, pathways that were less enriched in ILC were related to protein translation and metabolism, which we functionally validated in cell lines. The higher immune activity uncovered in our study highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC. Furthermore, the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/39 / 38/61 / 631/114 / 631/250 / 631/67/1347 / 82/79 / 96 / 96/106 / Aged / Atlases as Topic / Breast cancer / Breast carcinoma / Breast Neoplasms - diagnosis / Breast Neoplasms - genetics / Breast Neoplasms - immunology / Breast Neoplasms - metabolism / Carcinoma, Ductal, Breast - diagnosis / Carcinoma, Ductal, Breast - genetics / Carcinoma, Ductal, Breast - immunology / Carcinoma, Ductal, Breast - metabolism / Carcinoma, Lobular - diagnosis / Carcinoma, Lobular - genetics / Carcinoma, Lobular - immunology / Carcinoma, Lobular - metabolism / Cell Line, Tumor / Dormancy / Female / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Genome, Human / Humanities and Social Sciences / Humans / Immune response / Immune System - immunology / Immune System - metabolism / Immune System - pathology / Immunotherapy / Immunotherapy - methods / Invasiveness / Lymphatic Metastasis / Mammography / Metabolic Networks and Pathways - genetics / Metabolic Networks and Pathways - immunology / Metabolism / Middle Aged / multidisciplinary / Neoplasm Proteins - classification / Neoplasm Proteins - genetics / Neoplasm Proteins - immunology / Neoplasm Proteins - metabolism / Neoplasm Recurrence, Local - diagnosis / Neoplasm Recurrence, Local - genetics / Neoplasm Recurrence, Local - immunology / Neoplasm Recurrence, Local - metabolism / Protein Biosynthesis / Protein turnover / Proteins / Science / Science (multidisciplinary) / Translation / Tumor Escape - genetics