title: Biomarkers for the clinical management of breast cancer: international perspective.
abstract: The higher incidence of breast cancer in developed countries has been tempered by reductions in mortality, largely attributable to mammographic screening programmes and advances in adjuvant therapy. Optimal systemic management requires consideration of clinical, pathological and biological parameters. Oestrogen receptor alpha (ERα), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) are established biomarkers evaluated at diagnosis, which identify cardinal subtypes of breast cancer. Their prognostic and predictive utility effectively guides systemic treatment with endocrine, anti-HER2 and chemotherapy. Hence, accurate and reliable determination remains of paramount importance. However, the goals of personalized medicine and targeted therapies demand further information regarding residual risk and potential benefit of additional treatments in specific circumstances. The need for biomarkers which are fit for purpose, and the demands placed upon them, is therefore expected to increase. Technological advances, in particular high-throughput global gene expression profiling, have generated multi-gene signatures providing further prognostic and predictive information. The rational integration of routinely evaluated clinico-pathological parameters with key indicators of biological activity, such as proliferation markers, also provides a ready opportunity to improve the information available to guide systemic therapy decisions. The additional value of such information and its proper place in patient management is currently under evaluation in prospective clinical trials. Expanding the utility of biomarkers to lower resource settings requires an emphasis on cost effectiveness, quality assurance and possible international variations in tumor biology; the potential for improved clinical outcomes should be justified against logistical and economic considerations.
authors.affiliation: The Breakthrough Breast Cancer Research Center, The Institute of Cancer Research, London, United Kingdom.
authors.forename: Neill
authors.initials: N
authors.lastname: Patani
authors.forename: Lesley-Ann
authors.initials: LA
authors.lastname: Martin
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D015295:Antigens, Tumor-Associated, Carbohydrate / Q000097:blood; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism*; D002272:Carcinoembryonic Antigen / Q000097:blood; D049109:Cell Proliferation; D003362:Cost-Benefit Analysis; D019938:Cyclin D1 / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D004273:DNA, Neoplasm; D019049:Developed Countries / Q000706:statistics & numerical data; D003906:Developing Countries / Q000706:statistics & numerical data; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D014943:Global Health; D006295:Health Resources / Q000600:supply & distribution*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009360:Neoplastic Cells, Circulating; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis; D011785:Quality Assurance, Health Care; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D019396:Tissue Polypeptide Antigen / Q000097:blood; D059467:Transcriptome; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D019938:Cyclin D1; D019927:Cyclin E; D004273:DNA, Neoplasm; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019394:Ki-67 Antigen; D017395:Plasminogen Activator Inhibitor 1; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D019396:Tissue Polypeptide Antigen; D014568:Urokinase-Type Plasminogen Activator; C530104:CCND1 protein, human; C506487:ESR1 protein, human; C051321:SERPINE1 protein, human; C057387:mucinous carcinoma-associated antigen; C508053:ERBB2 protein, human