Aggressive form of breast cancer influenced by dual action of genes and RNA

Latina women are typically diagnosed at late stages with aggressive triple-negative breast cancer and could benefit from treatments targeted to the biology of their disease

WASHINGTON — Women with an aggressive, less-common type of breast cancer, known as triple-negative, versus a more common form of the disease, could be differentiated from each other by a panel of 17 small RNA molecules that are directly influenced by genetic alterations typically found in cancer cells.

Researchers lead by Luciane Cavalli, PhD, at Georgetown Lombardi Comprehensive Cancer Center, and colleagues found that variations in how these small RNA, known as microRNA (miRNA), are expressed, at higher or lower levels, could partially explain disparate rates of triple-negative breast cancer (TNBC) in Latina women compared to non-Hispanic white women and potentially lead to more effective treatment options.

That is the finding of a new study that was published October 22, 2019, in Oncotarget.

“Due to the variability in expression of miRNA by race or ethnicity, we determined that it was critical to characterize the genomic lineage (or ancestral background) of women with TNBC,” said Cavalli, an adjunct professor of medicine at Georgetown University School of Medicine and a faculty member at Instituto de Pesquisa Pele? Pequeno Pri?ncipe in Brazil. “While our focus was on genetics, we remain aware that non-genetic factors, such as social-economic conditions, can significantly impact the incidence rates of TNBC and other subtypes of breast cancer.”

Statisticians estimate that TNBC occurs in up to one-third of women in Latin American countries, a rate that is higher than in the United States. The researchers in this study focused on Brazil, in particular, where an estimated 60,000 new cases of breast cancer were diagnosed in 2018.

The scientists discovered that women with TNBC had specific alterations in copies of their genes that directly influenced the expression of 17 miRNAs compared to women with other forms of breast cancer who did not have these alterations. They also found that the expression levels of the majority of these miRNAs were associated with the tumor’s clinical aggressiveness (advanced grade and stage).

“The panel of miRNAs we identified indicate potential, critical cancer-related pathways and gene networks that could be targeted for the treatment of TNBC in Latinas, once our findings are validated by larger studies,” concluded Cavalli. “Targeting these genetic alterations, that represent the unique biology of their tumors, may lead to more efficient treatments, which could increase the longevity of Latina women who do not have many therapeutic options to fight this very aggressive disease.”

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In addition to Cavalli, authors include: Bruna M. Sugita, Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil and Faculdades Pequeno Príncipe, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, PR, Brazil; Silma R. Pereira, Department of Biology, Federal University of Maranhão, São Luis, MA, Brazil; Rodrigo C. de Almeida, Department of Biomedical Data Sciences, Section Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Mandeep Gill, Akanksha Mahajan, Anju Duttargi, and Saurabh Kirolikar, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center; Paolo Fadda, Genomics Shared Resource, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio; Rubens S. de Lima and Cicero A. Urban, Breast Unit, Hospital Nossa Senhora das Graças, Curitiba, PR, Brazil; Kepher Makambi, Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center; Subha Madhavan, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center and Innovation Center for Biomedical Informatics, Lombardi Comprehensive Cancer Center, Georgetown University; Simina M. Boca, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Innovation Center for Biomedical Informatics (ICBI), Lombardi Comprehensive Cancer Center, Georgetown University Medical Center; Yuriy Gusev, Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Innovation Center for Biomedical Informatics (ICBI), Lombardi Comprehensive Cancer Center, Georgetown University Medical Center; Iglenir J. Cavalli and Enilze M.S.F. Ribeiro, Department of Genetics, Federal University of Paraná, Curitiba, PR, Brazil.

The authors report no relationships or conflicts of interest to disclose relevant to this study.

This research was supported by the Georgetown University Center of Excellence in Regulatory Science and Innovation (CERSI; U01FD004319) and was partially supported by NIH/NCI grant P30-CA051008.

Sugita1 BM, Pereira SR, et al. Integrated copy number and miRNA expression analysis in triple
negative breast cancer of Latin American patients. Oncotarget. No. 58. Oct. 22, 2019.

About Georgetown Lombardi Comprehensive Cancer Center

Georgetown Lombardi Comprehensive Cancer Center is designated by the National Cancer Institute (NCI) as a comprehensive cancer center. A part of Georgetown University Medical Center, Georgetown Lombardi is the only comprehensive cancer center in the Washington D.C. area. It serves as the research engine for MedStar Health, Georgetown University’s clinical partner. Georgetown Lombardi is also an NCI recognized consortium with John Theurer Cancer Center/Hackensack Meridian Health in Bergen County, New Jersey. The consortium reflects an integrated cancer research enterprise with scientists and physician-researchers from both locations. Georgetown Lombardi seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic, translational and clinical research, patient care, community education and outreach to service communities throughout the Washington region, while its consortium member John Theurer Cancer Center/Hackensack Meridian Health serves communities in northern New Jersey. Georgetown Lombardi is a member of the NCI Community Oncology Research Program (UG1CA239758). Georgetown Lombardi is supported in part by a National Cancer Institute Cancer Center Support Grant (P30CA051008). Connect with Georgetown Lombardi on Facebook (Facebook.com/GeorgetownLombardi) and Twitter (@LombardiCancer).

About Georgetown University Medical Center

Georgetown University Medical Center (GUMC) is an internationally recognized academic health and science center with a four-part mission of research, teaching, service and patient care (through MedStar Health). GUMC’s mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis — or “care of the whole person.” The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization, which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health. Connect with GUMC on Facebook (Facebook.com/GUMCUpdate), Twitter (@gumedcenter).

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