neoadjuvant chemotherapy actually takes an important place in treatment of operable breast cancer in the hope of improving conservative surgery rate of female patients .
neoadjuvant chemotherapy includes today on target therapies involving the research on expression of specific molecules by tumoral cells . in routine practice , estrogen receptors ( er )
, progesterone receptors ( pr ) , and human epidermal growth factor receptor 2 ( her2 ) are the common used biomarkers .
new pharmaceutical molecules , other than er / pr or her2 , are now already evaluated in clinical research as new biomarkers and new target for neoadjuvant therapy .
fine - needle aspiration cytology ( fnac ) of the breast is wellknown as a safe , effective , economical , and accurate technique for diagnosing palpable breast lesion [ 24 ] .
this last decade , fnac technique is improved by the development of new cytological methods allowing standardization of fixation and assuring constant results with ancillary tests such as immunocytochemistry and in situ molecular biology .
also , one of the advantages of fnac is the management of small tissue fragments permitting a repetitive evaluation of the chronological evolution in expression of tumoral biomarkers .
previously , the role of fnac has been challenged by results obtained with cnb that seems more robust than fnac . in general ,
nevertheless , cnb carries disadvantage in terms of a long tissue processing time and patient discomfort such as pain ( 1.7% to 3.7% ) , hematoma ( 0.72% ) , and very rarely pneumothorax [ 6 , 7 ] .
fnac includes more advantages than cnb such as minimal invasiveness and minimal discomfort ( more painless ) that could be interesting for aged or frailty patients with comorbidities . in palpable lesions ,
fnac could perform repetitively and is a serious candidate for the chronological followup of neoadjuvant chemotherapy response .
an important quality of fnac is its ability to give rapid diagnostic information equivalent to that of frozen sections . in our experience
, the result of rapid fnac prior to cnb improves the quality of cnb and gives an immediate diagnosis decreasing anxiety of patient .  
other indications of fnac are staging of multiple tumors or suspicious zones and apparition of a new suspicious lesion during neoadjuvant chemotherapy .
finally , fnac could be an excellent alternative when radiographic screening of breast is not available .  
table 1 compares the main advantages and disadvantages of fnac versus cnb . 
 other clinical fnac indications . 

palpable breast lesion.rapid diagnosis to decrease anxiety of patient.patient with morbidity ( senile , cardiac , diabetic etc.).clinical staging : multiple lesions , suspicious lymph node , and so on .
apparition of new lesion in patient treated for breast cancer.evaluation of biomarkers.evaluation of biomarker changes following time or metastasis . when cnb technique is not available . 
 
evaluation of biomarker changes following time or metastasis .   when cnb technique is not available .
it is well known that the combination of clinical evaluation , mammography , and fnac , called triple diagnosis , gives a precise diagnosis [ 10 , 11 ] .
yu et al .   recently demonstrated in meta - analysis of 46 studies that fnac had a sensitivity of 92.7% and a specificity of 94.8% except the unsatisfactory samples .
the roc curve showed an excellent area under the curve of 0.986 , presenting a high level of accuracy . on the other hand ,
if the fnac result was negative , the probability of breast cancer is approximately 8% .
these authors concluded that fnac was an accurate material for evaluation on breast malignancy if rigorous criteria are used .
also , they said that fnac may provide a favourable screening method and permit an improvement of treatment planning .
therefore , when fnac is unsatisfactory , cnb is required to minimize the probability of a missed malignant diagnosis . in a study of fnac and immediate diagnosis performed in 408 palpable breast lesions , liew et al . in 2010  
reached the same conclusions : 98.1% sensitivity , 89.5% specificity , and 95.8% accuracy . in 508 cnb followed by jackman et al .
, the rate of false negative for all lesions was 4.4% , for microcalcifications alone 1.2% , and for tumoral mass 0.8% .
these results of cnb are quasi - identical to those obtained with the satisfactory fnac .
most of false negative fnac results of sampling error or discordance between clinical and histological observations [ 6 , 14 ] . in a comparison between cnb and repeat fnac after an indeterminate diagnosis with fnac , kooistra et al .  
suggested that cnb should be performed after an indeterminate fnac to obtain a reliable preoperative diagnosis .
other authors concluded that , although the fnac is easier to perform , this technique was not efficient for small and nonpalpable lesions or diagnosis of microcalcifications as those for in situ carcinoma .
these comments are likely true because some preneoplastic lesions are associated with slight cell atypia .
however , bilous   emphasized that cnb shows also problems with similar lesions such as atypical proliferative lesions ( atypical ductal hyperplasia , in situ lobular neoplasia , etc . ) , cellular fibroepithelial lesions , papillary tumors , mucinous carcinoma , radial scar , spindle cell lesions .
moreover , fnac interpretation requires serious experience of the cytopathologist and they think that this is one of the main reasons that overall cnb is to be preferred .   a recent japanese study   of 5693 fnac and 7 different laboratories illustrated a great variability between the institutions suggesting likely difference between education of cytologists and the lack of clinical or radiological information ( triple diagnosis ) .
these last years a new cytological technique , called liquid - based cytology ( lbc ) , has been developed and approved by the food and drug administration .
briefly , lbc standardises the cell fixation , concentrates epithelial cells , and discards blood cells and/or cell debris that obscure the smear .
the efficiency of lbc in the breast cytology has been demonstrated by numerous publications .  
the main advantage of lbc is surely to adjunct ancillary tests such as immunocytochemistry , flow cytometry , or molecular biology [ 1820 ] .
compared the er and pr statuses from fnac ( immunocytochemistry ) and cnb ( immunohistochemistry ) , both performed on surgical breast tumors .
they found that both methods give similar results with a concordance between the 2 tests of 98% for er ( with kappa correlation score = 0.93 ) and 96% for pr ( kappa = 0.91 ) .
.   demonstrated similar data in a comparative study between primary breast tumours and their metastasis .
interestingly , the concordance between these both localisations was 81% for er , 65% for pr , and 71% for her2 , suggesting a possibility of biological difference between primary tumors and their metastasis .  
other publications showed a long - time storage at 20c and 80c at least 6 months without significant loss of immunoreactivity of pr and ep from breast fnac .
the cell block cytology is an attractive cytological method for ancillary techniques or long - time cell conservations and consists in putting cells of fnac directly in formol fixative fluid identically at a classical histology ( figures 1 and 2 : er , her2 and fish on cell block cytology ) . briefly , after centrifugation to concentrate cells , the pellet was embedded in a synthetic polymer gel that is then processed in paraffin block that could be cut at 4  m , as classical biopsy slides . with this technique , ferguson et al .  
found a concordance rate of 95% for er , 90% for pr , and 88% for her2 .
similar results were observed by shabaik et al .   with high specificity ( 100% for both ) and lower sensibility ( 85% and 80% resp .
for er and pr ) . finally , in fnac , false negative er or pr immunostaining exists but false positive tests are very unlikely .
false negative immunohistochemical results are also observed in cnb : in a retrospective study , seferina et al .  
calculated a rate of false negative of 26.5% and a rate of false positive of 63.8% for both er and pr . for her2 , they showed 5.4% for false negative rate and 50% for false positive rate .
nevertheless , in our experience , this discordance is often associated with the manipulation of cnb before the fixation ( crush artefacts ) or with a defect of fixation as desiccation .
fortunately the concordance with molecular biology by hybridisation in situ using fish , cish , and sish is very good and can help when her2 is uncertain [ 6 , 25 , 27 ] .
the fish is accurate for lbc cytology [ 22 , 25 , 28 , 29 ] .
the extraction of mrna or dna is also feasible from lbc and fnac , allowing all gene expression analyses [ 2932 ] . in our experience ,
the clinical staging and preoperative lymph node status are important for the evaluation of eligible patient to neoadjuvant therapy . in the axillary lymph node fnac , chang et al .  
fnac in lymph node is a cost effective and safe method , false positive is virtually non - existent , and false negative can occur when lymph node is partially involved such as by micrometastase , or isolated tumor cells .   in our experience
, we improve axillary lymph node fnac / lbc by immunocytochemistry using cytokeratin antibody .  
thus , axillary fnac plays a role in staging of advanced cases for systemic and neoadjuvant therapy and in evaluating candidates for sentinel lymph node surgical procedure or axillary lymph node dissection .
despite the fact that cnb has been progressively replaced by fnac in the investigation of nonpalpable lesions or microcalcifications without a clinical or radiological mass lesion , fnac has yet a role in palpable lesions in the triple diagnosis association and performed by experienced cytologists . in these conditions , fnac is a safe , effective , economical , and accurate technique for breast cancer evaluation .  
recently , cytological methods using lbc technology , associated or not with the cellblock cytological technique , improve immunocytological and molecular tests with the same efficiency as classical histology .  
if the limits of its indications are well known , fnac still plays a role in the modern oncological practice .
 despite the fact that cnb has been progressively replaced by fnac in the investigation of nonpalpable lesions or microcalcifications without a clinical or radiological mass lesion , fnac has yet a role in palpable lesions provided it is associated with the triple diagnosis and experienced cytologist . in these conditions 
 , fnac is a safe , effective , economical , and accurate technique for breast cancer evaluation . 
 numerous literature reviews and meta - analyses illustrated the advantages and disadvantages of both methods cnb and fnac . 
 the difference does not seem significant when noninformative and unsatisfactory fnac was excluded . 
 recently , cytological methods using liquid - based cytology ( lbc ) technology improve immunocytological and molecular tests with the same efficiency as classical immunohistochemistry . 
 
 the indications of fnac were , for palpable lesions , relative contraindication of cnb ( elderly or frailty ) , staging of multiple nodules in conjunction or not with cnb , staging of lymph node status , newly appearing lesion in patient under neoadjuvant treatment , decreasing of anxiety with a rapid diagnosis , evaluation of biomarkers and new biomarkers , and chronological evaluation of biomarker following the neoadjuvant therapy response . 
1. Introduction
2. What Are the Advantages of FNAC in Comparison with Core-Needle Biopsy (CNB)?
3. Is the Diagnosis of FNAC Accurate?
4. What about Biomarkers?
5. Sentinel Lymph Node Evaluation by FNAC
6. Conclusions 