MOJ Immunology An Update on Breast Cancer Biomarkers Abstract Review Article Breast cancer is the most common cancer that affects millions of people Volume 5 Issue 2 - 2017 worldwide. Delayed diagnosis of these cancers has increased the morbidity and mortality. However, the vast research on cancer biomarkers during recent years provide a powerful and dynamic approach to understand the wide spectrum of cancers with applications in prognosis, diagnosis, screening, randomized clinical 1Centre for Applied Molecular Biology, University of the trials, and observational and analytic epidemiology. Cancer biomarkers have Punjab, Pakistan tremendously increased the efficacy of treatment and efficacy of detection. We 2Lahore College for Women University, Pakistan have comprehensively summarized various biomarkers of breast cancer and 3Lahore Garrison University, Defence Campus Lahore, Pakistan highlighted recent research. Braira Wahid, Centre for Applied Keywords: *Corresponding author: Baig, University of the Punjab, Lahore, Pakistan, Tel: +92-42- Biomarkers; Breast cancer; VEGF; Diagnosis Molecular Biology, 87-West Canal Bank Road Thokar Niaz 5293141; Fax: +92-42-5293149; Email: Received: | Published: Abbreviations: 2017 February 01, 2017 February 16, BC: Breast Cancer; EGFR: Epidermal Growth AA: AbirateroneFactor Receptor; Acetate VEGF: Vascular Endothelial Growth Factor; NSE: Neuron-Specific Enolase; MBC: Metastatic Breast Cancer; Introduction mutations have been detected in the hotspot regions of exon 9 and 20 of the PIK3CA in single circulating tumor cells of patients Breast cancer is the leading cause of death worldwide. In suffering from HER2-negative metastatic breast cancer [8]. 2013, Centre for Disease Prevention and Control documented that 230,815 women were diagnosed with breast cancer in United Based on candidate gene approach, large number of breast- States of which 40,860 women were died [1]. Delayed diagnosis cancer related methylation biomarkers have been discovered or limitations of mammography lead to poor prognosis of breast related gene such as APC [10], RASSF1A [11], and SOX17 [12]. for diagnosis of breast cancer gives false positive results, only Cohort-study[9]. As such, revealedregions identifiedthat methylated lie in CST6the promoters differentiated of cancerbreast observedcancer. Screen-film in aged women, mammography and is less sensitive (SFM) inthat women is being with denseused cancer samples from control samples. The study was based on breast tissue. There is dire need to overcome these limitations to two separate cohorts of breast-cancer patients including two improve the detection of breast cancer. Development of resistance separate cohorts of breast cancer patients, with methylation to chemotherapeutics is another factor contributing towards increased mortality. It is crucial to develop novel biomarkers individualsfound in 49/123 showed patients methylation (39.8%) [13]. in oneAnother cohort, retrospective and 14/73 patient’s treatment choice and drug resistance development [2]. study,patients based (19.2%) on 30 in healthyother cohort, controls while and none 36 earlyof the stage 37 healthy breast Thiswith reviewpotential article to confirm focuses diagnosis promising and biomarkers prognosis andfor diagnosis,to predict included CST6 for breast cancer. cancer patients showed that use of 8-gene biomarker panel (that prognosis, and prediction of which therapies will be efficacious ) provided highest sensitivity and specificity by Circulating DNA controlcorrectly samples identifying was also90% observed of cancer in negative this study samples [10]. and 91.7% of cancer samples. Significant level of CST6 methylation in the Circulating DNA is ideal and non-invasive biomarker isolated Likewise, another study evaluated the ability of circulating DNA to identify the tumors in 640 patients with diverse cancer amount of free DNA circulate in both diseased and healthy types. The results exhibited the presence of circulating DNA in humanfrom body serum fluids or plasmaespecially however, human an serum increased and plasma/serumplasma. Small concentration of DNA is observed in cancer patients because of gastroesophageal, hepatocellular, breast, ovarian, pancreatic, higher cellular turnover in cancer cells [3-5]. >75% patients with advanced head and neck cancers, melanoma, brain, and thyroid cancers. In patients with localized tumors, colorectal, and bladder and in <50% of primary prostate, renal, mutations such as TP53/ PIK3CA and PI3Kgene mutations in circulatingNext generation DNA has sequencingsuccessfully ofdemonstrated somatic tumor that trackingspecific of patients with pancreatic cancer, breast adenocarcinoma, gastroesophagealcirculating DNA wascancer, detected and colorectal in 48%, cancer, 50%, respectively57%, and [14].73% accurate and feasible tool for monitoring disease and therapy Another prospective study included 52 women of which 30 had tumor-specific circulating free DNA may provide valuable, in breast cancer patients [6,7]. Genomic aberration specifically genomic alterations in tumor samples that were patient specific Submit Manuscript | http://medcraveonline.com MOJ Immunol 2017, 5(2): 00150 Copyright: An Update on Breast Cancer Biomarkers ©2017 Wahid et al. 2/6 in this study circulating tumor DNA was found suitable for [26]. All these adjuvant therapies exhibited the association of PgR monitoringand tumor tumorspecific. cells Of [15]. three blood-born biomarkers assessed expressionPgR status hadlevel not and varied prognosis the efficacy of endocrine of letrozole therapy. over Evaluation tamoxifen of degree of correlation between immunohistochemical and immunocytochemical determination of PR and ER in breast cancer showed that both PR and ER were negative in nine cases but concentrationBaseline serum observed levels in cancerof circulating patients cell-free than in healthy DNA (ALU247, controls [16].ALU115) It has can been predict recently disease been reported prognosis that serumbecause cell-free of higher DNA support the use of ER and PR in prognosis of breast cancer [30]. CREBBP, SMAD4, AKAP9, PIK3CA, and TP53 positive in four cancer (PR in 1 and ER in 3). All these evidences act as biomarkers breast cancer patients receiving tamoxifen [17]. Androgen receptor (cfDNA) mutations in Estrogen receptor The androgen receptor is well-studied in context of male physiology because of its proven clinical target in prostate cancer. Expression of estrogen receptor acts as biomarker of breast Basal cytokeratins and androgen receptors provide powerful cancer, because it provides the index for sensitivity to endocrine prognostic information in triple-negative breast cancer [31]. treatment. Estrogen expression increased with age in breast Several studies show that association of breast cancer survival with AR status depends upon ER expression thus causing cancer patients [18]. Likewise, ER (estrogen receptor) level in ameliorated survival in ER+ tumors. The expression level of AR was inTDLU-PT postmenopausal (terminal women duct lobular [19]. A units- recent proximal study has to demonstrated tumor) and found to be considerably higher in endocrine responsive tumors. thatTDLU-DT neo-tanshinlactone (terminal duct lobulardecreased units-distal steady state to tumor) expression was higher level of ESR1 mRNA in ER+ breast cancer cells. Analysis of ER mRNA importance of AR for prognosis and survival outcome. The results levels and protein levels of target genes of transcription factor Multivariate analysis of disease free survival demonstrated the chemo-endocrine therapy and endocrine therapy thus, suggesting theof the prediction study exhibited of systematic that 90% treatments of ER-positive [32]. patientsWhereas, received in ER ERespecially negative GREB1, and PR CCND1,positive TFF1,breast BRCA1,cancer isESR2, not a reproducibleABCA3, and negative and triple negative breast cancer subset no prognosis subtype.SERPINB9 The further expression confirms of the progesterone aforementioned receptor finding is [20].not or poor prognosis impact of ER and AR negative tumor patients associated with prognosis of estrogen receptor negative breast was observed compared to ER-positive tumor patients. AR was cancer [21]. K303R ER mutation has been associated with breast found to be more frequently expressed than ER and PR in another cancer and benign breast hyperplasia [22]. An abiraterone acetate study that recruited 980 Chinese patients with invasive breast carcinoma. However, the expression of AR was closely associated progesterone and decrease serum androgen and estrogen levels. with PR and ER with higher level observed in ER+ subtypes than Dual(AA) expressionpharmacodynamic of ER and effect AR havein circulating been found tumor to cellsincrease and in ER- subtypes. It was related to more favorable pathological features such as marker of proliferation in breast cancer, lower Ki-67 expression and small tumor size [33]. isnewly being obtained investigated formalin-fixed as imaging paraffin-embedded biomarker to predict tissues tumor may Another retrospective study based on 287 females diagnosed aggressivenesspredict AA sensitivity in patients [23]. with Tumor estrogen-receptor-positive apparent diffusion coefficient breast therefore, it ER may serve as predictor of response to endocrine with TNBC (triple negative breast cancer) showed that AR were cancer [24]. ER-α is expressed in about 70% of breast cancers breast cancers. AR positivity was associated with longer overall survivalpresent andat rate disease of