title: Intratumor Heterogeneity in Breast Cancer.
abstract: Intratumor heterogeneity is the main obstacle to effective cancer treatment and personalized medicine. Both genetic and epigenetic sources of intratumor heterogeneity are well recognized and several technologies have been developed for their characterization. With the technological advances in recent years, investigators are now elucidating intratumor heterogeneity at the single cell level and in situ. However, translating the accumulated knowledge about intratumor heterogeneity to clinical practice has been slow. We are certain that better understanding of the composition and evolution of tumors during disease progression and treatment will improve cancer diagnosis and the design of therapies. Here we review some of the most important considerations related to intratumor heterogeneity. We discuss both genetic and epigenetic sources of intratumor heterogeneity and review experimental approaches that are commonly used to quantify it. We also discuss the impact of intratumor heterogeneity on cancer diagnosis and treatment and share our perspectives on the future of this field.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave. D740, 02215, Boston, MA, USA. francisco.beca@hms.harvard.edu.|IPATIMUP-Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal. francisco.beca@hms.harvard.edu.
authors.forename: Francisco
authors.initials: F
authors.lastname: Beca
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave. D740, 02215, Boston, MA, USA.|Department of Medicine, Harvard Medical School, Boston, USA.|Department of Medicine, Brigham and Women's Hospital, Boston, USA.
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor
keywords: Breast cancer; Clonality; Evolution; Heterogeneity; Phenotype; Progression; Resistance; Selection; Therapy