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Open AccessArticle

Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors

1
Division of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, 20122 Milan, Italy
2
School of Pathology, University of Milan, 20122, Milan, Italy
3
Research Laboratory Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122, Milan, Italy
4
Medical Genetics, Department of Pathophysiology and Transplantation, University of Milan, 20122, Milan, Italy
5
Pathology, Department of Biomedical, Surgical, and Dental Sciences, University of Milan, 20122, Milan, Italy
6
†These authors contributed equally to this work
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(3), 510; https://doi.org/10.3390/ijms20030510
Received: 20 December 2018 / Revised: 22 January 2019 / Accepted: 23 January 2019 / Published: 25 January 2019
(This article belongs to the Special Issue Sex Hormone Receptor Signals in Human Malignancies)
Estrogen receptor (ER)-positive progesterone receptor (PR)-negative breast cancers are infrequent but clinically challenging. Despite the volume of genomic data available on these tumors, their biology remains poorly understood. Here, we aimed to identify clinically relevant subclasses of ER+/PR− breast cancers based on their mutational landscape. The Cancer Genomics Data Server was interrogated for mutational and clinical data of all ER+ breast cancers with information on PR status from The Cancer Genome Atlas (TCGA), Memorial Sloan Kettering (MSK), and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) projects. Clustering analysis was performed using gplots, ggplot2, and ComplexHeatmap packages. Comparisons between groups were performed using the Student’s t-test and the test of Equal or Given Proportions. Survival curves were built according to the Kaplan–Meier method; differences in survival were assessed with the log-rank test. A total of 3570 ER+ breast cancers (PR− n = 959, 27%; PR+ n = 2611, 73%) were analyzed. Mutations in well-known cancer genes such as TP53, GATA3, CDH1, HER2, CDH1, and BRAF were private to or enriched for in PR− tumors. Mutual exclusivity analysis revealed the presence of four molecular clusters with significantly different prognosis on the basis of PIK3CA and TP53 status. ER+/PR− breast cancers are genetically heterogeneous and encompass a variety of distinct entities in terms of prognostic and predictive information. View Full-Text
Keywords: breast cancer; progesterone receptor negative; mutational profiling; PI3K pathway; TP53 breast cancer; progesterone receptor negative; mutational profiling; PI3K pathway; TP53
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MDPI and ACS Style

Lopez, G.; Costanza, J.; Colleoni, M.; Fontana, L.; Ferrero, S.; Miozzo, M.; Fusco, N. Molecular Insights into the Classification of Luminal Breast Cancers: The Genomic Heterogeneity of Progesterone-Negative Tumors. Int. J. Mol. Sci. 2019, 20, 510.

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