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Prognostic Significance of Interferon-? and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes.

ABSTRACT: Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-? (IFN-?) as a single gene as well as an IFN-? signature covering the signaling pathway in 461 breast cancer patients. Prognostic significance of IFN-?, as well as the IFN-? signature for metastasis-free survival (MFS), were examined using Kaplan-Meier as well as univariate and multivariate Cox regression analyses in the whole cohort and in different molecular subtypes. The independent prognostic significance of IFN-? as a single gene was limited to basal-like breast cancer (hazard ratio (HR) 2.779, 95% confidence interval (95% CI) 1.117-6.919, p = 0.028). In contrast, the IFN-?-associated gene signature was an independent prognostic factor in the whole cohort (HR 2.287, 95% CI 1.410-3.633, p < 0.001) as well as in the basal-like (HR 3.458, 95% CI 1.154-10.359, p = 0.027) and luminal B (HR 2.690, 95% CI 1.416-5.112, p = 0.003) molecular subtypes. These results underline the subtype-dependent prognostic influence of the immune system in early breast cancer.

SUBMITTER: Heimes AS

PROVIDER: S-EPMC7582264 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes.

Heimes Anne-Sophie AS Härtner Franziska F Almstedt Katrin K Krajnak Slavomir S Lebrecht Antje A Battista Marco J MJ Edlund Karolina K Brenner Walburgis W Hasenburg Annette A Sahin Ugur U Gehrmann Mathias M Hengstler Jan G JG Schmidt Marcus M

International journal of molecular sciences 20200929 19

Interferons are crucial for adaptive immunity and play an important role in the immune landscape of breast cancer. Using microarray-based gene expression analysis, we examined the subtype-specific prognostic significance of interferon-γ (IFN-γ) as a single gene as well as an IFN-γ signature covering the signaling pathway in 461 breast cancer patients. Prognostic significance of IFN-γ, as well as the IFN-γ signature for metastasis-free survival (MFS), were examined using Kaplan-Meier as well as u ...[more]

PMID: 33003293

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Project description:ImportanceIt is unclear whether ERBB2-low breast cancer should be considered an individual biologic subtype distinct from ERBB2-0 breast cancer.ObjectiveTo investigate whether low ERBB2 expression is associated with distinct clinicopathologic characteristics and prognosis among patients with hormone receptor (HR)-positive and triple-negative breast cancer (TNBC).Design, setting, and participantsThis cohort study was conducted using data from a prospectively maintained institutional database on all consecutive patients with breast cancer undergoing surgery between January 2016 and March 2021 at Dana-Farber Brigham Cancer Center. The study included 5235 patients with stage I through III, ERBB2-negative invasive breast cancer. Tumors were classified as ERBB2-low if they had an ERBB2 immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization assay and ERBB2-0 if they had an ERBB2 IHC score of 0. Data were analyzed from September 2021 through January 2022.ExposuresStandard treatment according to institutional guidelines.Main outcomes and measuresComparison of clinicopathologic characteristics and disease outcomes (pathologic complete response rate [pCR], disease-free survival, distant disease-free survival, and overall survival) between patients with ERBB2-low and ERBB2-0 breast cancer.ResultsAmong 5235 patients with ERBB2-negative invasive breast cancer (5191 [99.2%] women; median [range] age at primary surgery, 59.0 [21.0-95.0] years), 2917 patients (55.7%) and 2318 patients (44.3%) had ERBB2-low and ERBB2-0 tumors, respectively. Expression of HR was significantly more common among ERBB2-low compared with ERBB2-0 tumors (2643 patients [90.6%] vs 1895 patients [81.8%]; P < .001). The rate of ERBB2-low tumors increased progressively, from 296 of 739 estrogen receptor (ER)-negative tumors (40.1%) to 31 of 67 ER-low (ie, ER 1%-9%) tumors (46.3%), 37 of 67 ER-moderate (ie, ER, 10%-49%) tumors (55.2%), 2047 of 3542 ER-high (ie, ER, 50%-95%) tumors (57.8%), and 499 of 803 ER-very high (ie, ER > 95%) tumors (62.1%) (P < .001). Among 675 patients receiving neoadjuvant chemotherapy, those with ERBB2-0 tumors experienced higher pCR rates (95 patients [26.8%] vs 53 patients [16.6%]; P = .002). However, there were no statistically significant differences in pCR rate between ERBB2-low and ERBB2-0 tumors when separately analyzing HR-positive, ER-low, HR-positive without ER-low, or TNBC tumors. In exploratory survival analysis, no differences by ERBB2-low expression in disease-free survival, distant disease-free survival, or overall survival were observed among patients with HR-positive tumors or TNBC.Conclusions and relevanceThe results of this cohort study did not support the interpretation of ERBB2-low breast cancer as a distinct biologic subtype. ERBB2-low expression was positively associated with level of ER expression, and ER-low tumors were enriched among ERBB2-0 tumors, suggesting that, given the worse prognosis of ER-low tumors, they may be associated with confounding of prognostic analyses of ERBB2-low expression.

Dataset Information

Prognostic Significance of Interferon-? and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes.

Publications

Prognostic Significance of Interferon-γ and Its Signaling Pathway in Early Breast Cancer Depends on the Molecular Subtypes.

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