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The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection

Open access
Lehmann, Brian D., Jovanović, Bojana, Chen, Xi, Estrada, Monica V., Johnson, Kimberly N., Shyr, Yu, Moses, Harold L., Sanders, Melinda E., Pietenpol, Jennifer A.·2016·PLOS ONE
DOI 10.1371/journal.pone.0157368
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Abstract

Triple-negative breast cancer (TNBC) is a heterogeneous disease that can be classified into distinct molecular subtypes by gene expression profiling. Considered a difficult-to-treat cancer, a fraction of TNBC patients benefit significantly from neoadjuvant chemotherapy and have far better overall survival. Outside of BRCA1/2 mutation status, biomarkers do not exist to identify patients most likely to respond to current chemotherapy; and, to date, no FDA-approved targeted therapies are available for TNBC patients. Previously, we developed an approach to identify six molecular subtypes TNBC (TNBCtype), with each subtype displaying unique ontologies and differential response to standard-of-care chemotherapy. Given the complexity of the varying histological landscape of tumor specimens, we used histopathological quantification and laser-capture microdissection to determine that transcripts in the previously described immunomodulatory (IM) and mesenchymal stem-like (MSL) subtypes were contributed from infiltrating lymphocytes and tumor-associated stromal cells, respectively. Therefore, we refined TNBC molecular subtypes from six (TNBCtype) into four (TNBCtype-4) tumor-specific subtypes (BL1, BL2, M and LAR) and demonstrate differences in diagnosis age, grade, local and distant disease progression and histopathology. Using five publicly available, neoadjuvant chemotherapy breast cancer gene expression datasets, we retrospectively evaluated chemotherapy response of over 300 TNBC patients from pretreatment biopsies subtyped using either the intrinsic (PAM50) or TNBCtype approaches. Combined analysis of TNBC patients demonstrated that TNBC subtypes significantly differ in response to similar neoadjuvant chemotherapy with 41% of BL1 patients achieving a pathological complete response compared to 18% for BL2 and 29% for LAR with 95% confidence intervals (CIs; [33, 51], [9, 28], [17, 41], respectively). Collectively, we provide pre-clinical data that could inform clinical trials designed to test the hypothesis that improved outcomes can be achieved for TNBC patients, if selection and combination of existing chemotherapies is directed by knowledge of molecular TNBC subtypes.

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Metadata

Authors
Lehmann, B. D., Jovanović, B., Chen, X., Estrada, M. V., Johnson, K. N., Shyr, Y., Moses, H. L., Sanders, M. E., & Pietenpol, J. A.
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2016-06-16
Volume
11
Issue
6
Pages
e0157368
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0157368
OpenAlex
W2430731787
Cited by
1,426
References
37
FWCI
33.72
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. https://app.cochat.ai/papers/10.1371/journal.pone.0157368
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Lehmann, B. D., Jovanović, B., Chen, X., Estrada, M. V., Johnson, K. N., Shyr, Y., Moses, H. L., Sanders, M. E., & Pietenpol, J. A. (2016). Refinement of Triple-Negative Breast Cancer Molecular Subtypes: Implications for Neoadjuvant Chemotherapy Selection. PLOS ONE. https://doi.org/10.1371/journal.pone.0157368

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.