Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment.
BACKGROUND
Every year about one million women worldwide are diagnosed with breast cancer which is the most common malignancy in female. Of these, triple negative breast carcinoma represents 10-17 %. Triple negative breast carcinomas, characterized by estrogen, progesterone and HER2 receptor negativity are very aggressive tumours with poor prognosis. Individualized treatment (tailored therapy) based on molecular biology markers of tumor and patient is the trend in clinical practice these days. However, molecular targets and predictors for the treatment of triple negative breast carcinoma do not currently exist.


RESULTS
This minireview focuses on biomarkers (HER1/EGFR, TOP2A and C-MYC genes) that may predict the response of triple negative breast carcinoma patients to chemotherapy and/or targeted biological treatment with a summary of current knowledge about them.


CONCLUSIONS
HER1 belonging to the HER family of receptors plays an important role in cell proliferation, migration and protection against apoptosis. HER1 protein could be targeted by monoclonal antibodies and/or tyrosine kinase inhibitors (TKIs). Given signal pathway complexity and HER family member cooperation, it may be better to simultaneously target a number of these receptors (e.g. HER1/HER2 by lapatinib). Thus, HER1 assessment could reveal a particular breast cancer patient group with probably good response to HER1 targeted therapy. TOP2A gene, encoding topoisomerase II alpha (target for anthracyclines) is predictive of response to anthracycline therapy. TOP2A aberrations (amplification, deletion) are found in up to approximately 30-90 % of HER2 amplified breast cancer and amplifications are more common than deletions. Recent publications describe TOP2A amplification also in 2.7-8.8 % HER2 nonamplified breast cancers. Patients with a pathologic complete response to anthracycline based neoadjuvant chemotherapy had a good overall prognosis regardless of molecular subtype of breast cancer. These results suggest that particularly tumors with a complete pathological response to anthracyclines could have TOP2A amplification. C-MYC encodes nuclear DNA binding proteins that regulate proliferation and apoptosis; amplification is associated with poor prognosis and hormonally negative breast carcinoma.
Department of Paediatrics, Faculty of Medicine and Dentistry, Laboratory of Experimental Medicine, Palacky University and University Hospital, Olomouc, Czech Republic. hajduchm@gmail.com
Katerina
K
Bouchalova
Magdalena
M
Cizkova
Karel
K
Cwiertka
Radek
R
Trojanec
Marian
M
Hajduch
D000951:Antigens, Neoplasm / Q000032:analysis / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000032:analysis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D005260:Female; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D015609:Organotechnetium Compounds; D010091:Oximes; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D015609:Organotechnetium Compounds; D010091:Oximes; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C105527:technetium Tc 99m 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C000618811:TOP2A protein, human