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Immune landscape of breast tumors with low and intermediate estrogen receptor expression.

ABSTRACT: Immune checkpoint blockade (ICB) is currently approved for patients with triple-negative breast cancer (TNBC), whereas responses to ICB are also observed in a small subgroup of Estrogen Receptor (ER)-positive breast cancer. The cut-off for ER-positivity (≥1%) is based on likelihood of endocrine treatment response, but ER-positive breast cancer represents a very heterogeneous group. This raises the question whether selection based on ER-negativity should be revisited to select patients for ICB treatment in the context of clinical trials. Stromal tumor-infiltrating lymphocytes (sTILs) and other immune parameters are higher in TNBC compared to ER-positive breast cancer, but it is unknown whether lower ER levels are associated with more inflamed tumor microenvironments (TME). We collected a consecutive series of primary tumors from 173 HER2-negative breast cancer patients, enriched for tumors with ER expression between 1 and 99% and found levels of stromal TILs, CD8 + T cells, and PD-L1 positivity in breast tumors with ER 1-9% and ER 10-50% to be comparable to tumors with ER 0%. Expression of immune-related gene signatures in tumors with ER 1-9% and ER 10-50% was comparable to ER 0%, and higher than in tumors with ER 51-99% and ER 100%. Our results suggest that the immune landscape of ER low tumors (1-9%) and ER intermediate tumors (10-50%) mimic that of primary TNBC.

SUBMITTER: Voorwerk L

PROVIDER: S-EPMC10182974 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Immune landscape of breast tumors with low and intermediate estrogen receptor expression.

Voorwerk Leonie L Sanders Joyce J Keusters Milou S MS Balduzzi Sara S Cornelissen Sten S Duijst Maxime M Lips Esther H EH Sonke Gabe S GS Linn Sabine C SC Horlings Hugo M HM Kok Marleen M

NPJ breast cancer 20230513 1

Immune checkpoint blockade (ICB) is currently approved for patients with triple-negative breast cancer (TNBC), whereas responses to ICB are also observed in a small subgroup of Estrogen Receptor (ER)-positive breast cancer. The cut-off for ER-positivity (≥1%) is based on likelihood of endocrine treatment response, but ER-positive breast cancer represents a very heterogeneous group. This raises the question whether selection based on ER-negativity should be revisited to select patients for ICB tr ...[more]

PMID: 37179445

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Project description:BackgroundMany breast cancer patients remain free of distant metastasis even without adjuvant chemotherapy. While standard histopathological tests fail to identify these good prognosis patients with adequate precision, analyses of gene expression patterns in primary tumors have resulted in more successful diagnostic tests. These tests use continuous measurements of the mRNA concentrations of numerous genes to determine a risk of metastasis in lymph node negative breast cancer patients with other clinical traits.MethodsA survival model is constructed from genes that are both connected with relapse and have expression patterns that define distinct subtypes, suggestive of different cellular states. This in silico study uses publicly available microarray databases generated with Affymetrix GeneChip technology. The genes in our model, as represented by array probes, have distinctive distributions in a patient cohort, consisting of a large normal component of low expression values; and a long right tail of high expression values. The cutoff between low and high expression of a probe is determined from the distribution using the theory of mixture models. The good prognosis group in our model consists of the samples in the low expression component of multiple genes.ResultsHere, we define a novel test for risk of metastasis in estrogen receptor positive (ER+) breast cancer patients, using four probes that determine distinct subtypes. The good prognosis group in this test, denoted AP4-, consists of the samples with low expression of each of the four probes. Two probes target MKI67, antigen identified by monoclonal antibody Ki-67, one targets CDC6, cell division cycle 6 homolog (S. cerevisiae), and a fourth targets SPAG5, sperm associated antigen 5. The long-term metastasis-free survival probability for samples in AP4- is sufficiently high to render chemotherapy of questionable benefit.ConclusionA breast cancer subtype defined by low expression of a few genes, using a minimum of statistical modeling, has significant prognostic power. This test is of potential clinical benefit in deciding a course of treatment for early stage breast cancer patients.

Dataset Information

Immune landscape of breast tumors with low and intermediate estrogen receptor expression.

Publications

Immune landscape of breast tumors with low and intermediate estrogen receptor expression.

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