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How many diseases is triple negative breast cancer: the protagonism of the immune microenvironment.

ABSTRACT: Triple negative breast cancer (TNBC) is a type of breast cancer (BC) that does not express the oestrogen and the progesterone receptors and the human epidermal growth factor receptor type 2 (HER2). Since there are no positive markers to reliably classify TNBC, these tumours are not yet treated with targeted therapies. Perhaps for this reason they are the most aggressive form of breast carcinomas. However, the clinical observation that these patients do not carry a uniformly dismal prognosis, coupled with data coming from pathology and epidemiology, suggests that this negative definition is not capturing a single clinical entity, but several. We critically evaluate this evidence in this paper, reviewing clinical and epidemiological data and new studies that aim to subclassify TNBC. Moreover, evidence on the role of tumour infiltrating lymphocytes (TILs) on TNBC progression, response to chemotherapy and patient outcome have been published. The heterogeneity, observed even at TILs level, highlights the idea that TNBC is much more than a single disease with a unique treatment. The exploration of the immune environment present at the tumour site could indeed help in answering the question 'How many diseases is TNBC' and will help to define prognosis and eventually develop new therapies, by stimulating the immune effector cells or by inhibiting immunological repressor molecules. In this review, we focus on the prospect of the patient's diverse immune signatures within the tumour as potential biomarkers and how they could be modulated to fight the disease.

SUBMITTER: Saraiva DP

PROVIDER: S-EPMC5604720 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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How many diseases is triple negative breast cancer: the protagonism of the immune microenvironment.

Saraiva Diana P DP Guadalupe Cabral M M Jacinto António A Braga Sofia S

ESMO open 20170914 4

Triple negative breast cancer (TNBC) is a type of breast cancer (BC) that does not express the oestrogen and the progesterone receptors and the human epidermal growth factor receptor type 2 (HER2). Since there are no positive markers to reliably classify TNBC, these tumours are not yet treated with targeted therapies. Perhaps for this reason they are the most aggressive form of breast carcinomas. However, the clinical observation that these patients do not carry a uniformly dismal prognosis, cou ...[more]

PMID: 29018573

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Project description:PurposeAfrican-American (AA) patients with triple-negative breast cancer (TNBC) are less likely to achieve pathologic complete response from neoadjuvant chemotherapy and have poorer prognosis than Caucasian patients with TNBC, suggesting potential biological differences by race. Immune infiltration is the most consistent predictive marker for chemotherapy response and improved prognosis in TNBC. In this study, we test the hypothesis that the immune microenvironment differs between AA and Caucasian patients.MethodsRNA-seq expression data were obtained from The Cancer Genome Atlas (TCGA) database for 162 AA and 697 Caucasian breast cancers. Estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-positive, and TNBC subtypes were included in the analyses. Tumor infiltrating lymphocyte (TIL) counts, immunomodulatory scores, and molecular subtypes were obtained from prior publications for a subset of the TNBC cases. Differences in immune cell distributions and immune functions, measured through gene expression and TIL counts, as well as neoantigen, somatic mutation, amplification, and deletion loads, were compared by race and tumor subtype.ResultsImmune metagene analysis demonstrated marginal immune attenuation in AA TNBC relative to Caucasian TNBC that did not reach statistical significance. The distributions of immune cell populations, lymphocyte infiltration, molecular subtypes, and genomic aberrations between AA and Caucasian subtypes were also not significantly different. The MHC1 metagene demonstrated increased expression in AA ER-positive cancers relative to Caucasian ER-positive cancers.ConclusionsThis study suggests that the immunological differences between AA and Caucasian breast cancers represented by TCGA data are subtle, if they exist at all. We observed no consistent racial differences in immune gene expression or TIL counts in TNBC by race. However, this study cannot rule out small differences in immune cell subtype distribution and activity status that may not be apparent in bulk RNA analysis.

Dataset Information

How many diseases is triple negative breast cancer: the protagonism of the immune microenvironment.

Publications

How many diseases is triple negative breast cancer: the protagonism of the immune microenvironment.

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