Comparison of fine needle aspiration cytology and core needle biopsy findings with excisional biopsy in breast malignancy

Biopsy; Breast; Cytology; Estrogen receptor; HER-2/neu; Large-Core Needle; Background: Fine needle aspiration cytology and core needle biopsy are reliable procedures for breast cancer detection. Core needle biopsy is an established alternative to surgical biopsy for diagnosis and prognostication. However, there may be a concern that core needle biopsy may be less reliable than excisional biopsy. The aim of this study was to compare the cytological/core needle biopsy finding with excisional histopathological diagnosis and determine their hormonal status.


INTRODUCTION
Breast cancer is a heterogeneous disease at the clinical, morphological and molecular levels with varied responses to therapy.Pre-operative pathology diagnosis constitutes an essential part of the work-up of breast lesions.The role of Fine needle aspiration (FNA) is a less traumatic alternative to core needle biopsy (CNB) and the main goal is to confirm benign clinical and radiological findings in order to avoid unnecessary surgery.1-2 Advantage of CNB is the ability to diagnose invasiveness and thus allow the patient to undergo a single operation including sentinel node biopsy in cases diagnosed as invasive.Hormone receptor status and surface epithelial growth-factor receptors are the main predictive factor. 3This study thus helps us to categorize different histological types of breast malignancy and to determine their ER, PR and HER-2/neu status which carries both the prognostic and predictive significance.

MATERIALS AND METHODS
A prospective study was carried out after ethical clearance from the institutional review board.The study was carried out form 14th April 2017 to 13th April 2018 among patients visiting Tribhuvan University Teaching Hospital, Maharajgunj and was suspected of having breast carcinoma based upon clinical and radiological examination.After obtaining a detailed clinical data, the patient was subjected to FNAC or core needle biopsy.The consent of the patient was taken before the procedure.The data collection was done in predesigned proforma and data entry was done in SPSS and results were computed using Statistical Package for Social Sciences (SPSS) version 20.Frequency calculation and cross tabulation were done for data analysis.

RESULTS
During the study period, a total of 472 patients underwent FNAC for breast lump.Among them 190 cases had breast mass excised.Among all 472 patients with a breast lump, 65 cases were clinically/radiologically suspected for breast carcinoma.The age of the patients with suspicion of breast carcinoma ranged from 26 years to 82 years with a mean age of 47.38±11.9years.The most common age group was 40-49 years.Most of the patients were female ( n=63; 96.9%) with 2 (3.1%) male patients.Almost half of the total 65 suspected cases of breast cancer (50.8% ) were on oral contraceptive pills, 2/3 (65.1%) cases were multiparous, 15.9% women had given birth to a single child and 19% women were nulliparous.The most common age of menarche was 13 years (23.8%) and 14 years (23.8%).Among the study population, 28 (42.9%)cases were postmenopausal women.The average age of menopause was 47.85±2.4years.Among all the suspected patients, 4 (6.2%)patients had a positive family history for breast cancer.
Of all 65 patients, the right breast was slightly more involved by carcinoma (50.8%) than the left one (47.7%).Bilateral breasts were involved in 1.5% of cases.Forty two (64.6%)patients presented with breast mass in the upper outer quadrant followed by retroareolar area (12.3%).
19 cases had undergone both the FNA and CNB.Among them, 13 cases were ductal carcinoma in FNAC and in CNB 12 cases turned out to be Invasive carcinoma of no special type, one case was inadequate.FNA and CNB findings showed good concordance (Table 2).
Comparison of CNB with excisional biopsy findings revealed that out of 35 CNB cases, 25 cases of Invasive carcinoma of no special type in CNB, 24 (96%) cases correlate well with excisional biopsy findings.One case DOI 10.3126/jpn.v9i2.250313).
Hormonal status were assessed in 45 cases, triple negative was the commonest type followed by ER Positive, PR Positive, HER-2/neu Negative (Table 5).The frequencies of ER/PR and HER-2/neu status were assessed according to tumor grade (I, II and III).Triple negative cases were more common in Grade III Invasive carcinoma of no special type compared to grade II and grade I. ER+/PR+ and HER-2/neu negative status were most common in grade I and grade II carcinoma.

DISCUSSION
Breast lesions can usually be detected using various imaging modalities, they are not always typical in appearance and might need cytological or histopathological examination for definitive diagnosis. 4Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently and thus carries prognostic and predictive value. 5his study reflects the comparability between FNAC and CNB in the diagnosis of breast carcinoma considering the histological diagnosis from the excision specimen being the gold standard.
Carcinoma was most commonly diagnosed in the age group of 40-49 years in female patients (40%) followed by in the group of 30-39 and 50-59 years (21.5% each).In a study by Thapa et al. out of the 944 female breast cancer patients, 263 (27.9%) were <40 years 6 .The mean age was 34.6 ± 5.0 years among younger patients compared to 54.1 ± 9.9 for those ≥ 40 years. 6As per data from seven major cancer hospitals in Nepal the highest incidence rate of breast cancer was in the age of 45-49 followed by the 55-59 years group. 7s per larger studies on sex-incidence of breast carcinoma, it is an uncommon neoplastic condition in men, accounting for not more than 1% of all breast carcinomas. 8We found 3.1% of the study population was male.This discrepancy was most probably due to the selection of a lesser number of patients in the study.
The relationship between oral contraceptives pills (OCPs) and breast cancer is controversial.In the year 1996, a study that reviewed the use of OCPs resulted only in a small increase in risk (relative risk=1.24)for breast cancer. 9here was no significant difference in the development of breast cancer during 10 years after the discontinuation of oral contraceptive use.Ban and Godellas conducted a recent study where they reported that women taking oral contraceptives had a 24% higher risk of developing cancer compared to those who never took them in their lives and that this risk especially materialized during the use of oral contraceptives. 10Changes in the formulation of oral contraceptives overtime, the duration of their use and different oral contraceptive formulation may result in a differentiation of breast cancer risk.In the present study, 50.8% of cases with breast cancer were using OCPs.The risk of breast cancer declines with the number of children born.Women who have given birth to five or more children have half the breast cancer risk of women who have not given birth.Some evidence indicates that the reduced risk associated with a higher number of births may be limited to hormone receptor-positive breast cancer. 11In our study, 65.1% cases of women with breast cancer were multiparous, 15.9% of women had given birth to a single child and 19% of women were nulliparous.This corresponds to the study performed by Balekouzou et al. 12 9 In the present study, 6.2% of all the cases with breast cancer had a positive family history.Of all 65 patients in our study, the right breast was slightly more involved by carcinoma (50.8%) than left one (47.7%)followed by bilateral (1.5%).Aljarrah et al. stated that breast cancer occurs almost equally in the right and left breast and most commonly affected the upper outer quadrant (UOQ). 13mong all 65 patients in this study, 42 patients i.e. 64.6% presented with breast mass in upper outer quadrant of the breast followed by retroareolar area (12.3%).Deen et al. in their study had found that 46.12% of patients in whom upper outer quadrant was involved in breast cancer. 14The larger mass of breast tissue in the upper outer quadrant is responsible for the commonest occurrence at this location.
Early breast cancers situated in central/internal quadrants have a worse prognosis compared with those in lateral quadrants, that is why tumor location is an important part in prognosis in terms of distant metastases and survival. 13 the present study 69.2% (n=45) cases had undergone FNAC, 60% (n=39) cases core needle biopsy and 93.8% (n=61) cases excisional biopsy.All three procedures were performed in 23% (n= 15) cases.Most of the cases had undergone modified radical mastectomy (82% cases) followed by breast conserving surgery (16.4% cases).In a study by Thapa et the proportion of breast conserving surgery was higher in young patients (25.1% vs. 8.7%) compared to modified radical mastectomy. 6However, in our study, most of the breast conserving surgery was performed in an elderly female.This reason may be due to the increased risk of morbidity in radical surgery in elderly patients.
A  1).The inadequacy may be due to fibrotic mass and ill defined lesion.In a study by Uddin Rupom et al., the overall diagnostic accuracy of FNAC was 100%. 15This may be due to smaller sample size and repeated FNA procedure in inadequate cases.On comparing categorization (C-category) done through FNAC with histopathological findings in the study performed by M. Shaila K et al. all the malignant (C5) categories turned out to be malignant histologically. 16e tru-cut biopsy of palpable breast lesions based on a histological study of tissue specimens can provide all the reliable information.For small non-palpable lesions in breast lumps, tru-cut biopsy has replaced FNAC because sample insufficiency is rare for tru-cut biopsy even for these lesions.In this study, 19 cases had undergone both the FNA and CNB.The most common diagnosis in both the procedure was invasive carcinoma of no special type.A single case inadequate by FNAC was diagnosed in CNB.In a study performed by P. Garg et al. 29 cases were diagnosed as malignant on FNAC only 26 cases were diagnosed as malignant on CNB with 3 cases signed out as non-diagnostic for malignancy owing to non-sampling from the representative areas. 17Shashirekha et al. in their study concluded that in an experienced hand, the sensitivity of FNAC is high.Also, the inadequacy rate of FNAC for non-palpable lesions, the incidence of which has increased.However, it was almost similar in the current study.So, the overall performance indices of CNB are superior to FNAC in the majority of breast lesions. 18udies carried out by Usami S et al, to compare CNB & FNAC have reported very high sensitivity (91-99%), specificity (96-100%), positive predictive value (100%) and negative predictive value (100%) for CNB which are better than results for FNAC for both palpable and nonpalpable lesions. 19This concords with the findings of this study.
Compared to open surgery, tru-cut biopsy is much less invasive.For non-palpable lesions, surgery is omitted when the pathology is benign.It is a reliable method for histopathological diagnosis and offers the advantage over fine needle aspiration of providing enough material to perform IHC.However, there may be a concern that CNB may be less reliable than excisional biopsy due to the smaller sample size, sampling error on the heterogeneous tumor and/or crush artifacts in the CNB.This has major clinical implications since the expression of markers such as ER, PR and HER-2/neu will guide therapeutical planning. 17For malignant lesions, surgery can be done in a single setting.
A comparison of CNB with excisional biopsy findings revealed that CNB had 92.30 % sample adequacy in diagnosing breast carcinoma.Sixty-nine patients with a breast CNB diagnosed as carcinoma followed by surgical excision of the tumor were assessed by Ricci et al. 20 Similar to our study the histologic types determined in core biopsy correlated with the types determined in surgical biopsy (Table 3).In a study by Tamaki K et al 2 the cases that received four cores reached to 100% concordance in diagnosis between CNB and surgical specimens in contrast to our study.We had 85% concordance in correct histological subtyping.The reason may be due to presence only one or two numbers of cores taken as we just started CNB in our institute.
Of the total 65 cases, 93.84% cases had undergone excisional biopsy and of these 87.69% cases of invasive carcinoma were graded according to the Elston-Ellis modification of Scarff-Bloom-Richardson grading system.WHO stated invasive carcinoma of no special type is the most common type of invasive carcinoma in breast comprising between 40% and 75% in different published series followed by invasive lobular carcinoma in 5-15% cases. 21In different studies, invasive carcinoma of no special type was seen in most (92.8%) of the patients followed by invasive lobular carcinoma (2.9%) and medullary carcinoma (1.4%). 22A retrospective study of the clinico-pathological spectrum of carcinoma breast in a West Delhi, India by Nigam et al, showed that invasive carcinoma of no special type was the commonest variant comprising of 81.40% of cases followed by medullary carcinoma 10.36% and mucinous carcinoma 2.74%. 23The distribution of histological types of breast carcinoma in the present study population was almost similar to that of other reported series.
In the present study, the most common histological grade was grade II (44.3%) followed by grade I (31.1%) and grade III (24.6%) tumors.In comparison to our study, in a study performed by K. Geethamala et.al, the most common histologic grade encountered was grade II accounting to 54% followed by grades III and I with 27% and 19% respectively.24 The largest and most well-known study on histological grading by Elston and Ellis found 342 cases (19%) of grade I, 631 cases (34%) of grade II, and 857 cases (47%) of grade III tumors. 22trogen receptor and progesterone receptor determinations are established procedures in the routine management of patients with breast cancer, primarily as predictive factors for response to therapeutic and adjuvant hormonal therapy. 25n the present study, there was a greater proportion of , our results provide valuable prognostic information to guide the decision-making process for the treatment of the patient with invasive carcinoma.

CONCLUSIONS
Fine needle aspiration cytology of breast lesions is a safe, simple, minimally invasive, cost effective and sensitive method for cytological diagnosis.However, CNB was superior to FNAC in the diagnosis of breast lesions in terms of diagnostic accuracy and correct typing of benign and malignant cases.Thus, CNB is more specific and cost effective in giving a definitive histopathological diagnosis, therefore, avoiding unnecessary surgical management and can be used as an alternative to open biopsy.It also gives further information about tumor grade, lympho-vascular invasion, and receptor status.Biomarker status can be performed in a CNB specimen.The present study concludes that CNB permits the categorization of various types of breast malignancies which is helpful for the management of the patient.Thus, our results provide valuable prognostic and predictive information to guide the decision-making process for the treatment of a patient with invasive carcinoma.

Figure 1 :
Figure 1: Histological section of Invasive carcinoma of no special type, Grade III showing moderately pleomorphic tumor cells arranged in solid sheets (HE stain, X200).These cells are HER-2/neu positive (inset, IHC, X400).
) constituted of 74.4%, Invasive lobular carcinoma, and malignant phyllodes tumor 7.7% each and Invasive micropapillary carcinoma (fig.2) 2.6%.7.7% of cases were inadequate for diagnosis.The most common diagnosis in FNAC was ductal carcinoma and in excisional biopsy 23 cases turned out to be Invasive carcinoma of no special type, one case Multifocal invasive carcinoma, one case Carcinoma with medullary features and two cases Metaplastic carcinoma (Table

or needle biopsy vs. excisional in breast malignancy done
by B. Thapa et al. family history of breast cancer was evident in 3.0% of the young women versus 0.3% in the older one.
9which was more similar to our study.Approximately 3-10% of breast cancer cases are hereditary cancers.It is stated that approximately 85% of them are associated with BRCA1 and BRCA2 mutations.9Thesemutations were not assessed in the current study.In a study Bhatta U et al DOI 10.3126/jpn.v9i2.25031Cytology 27rmonal receptor status has shown that the overall positivity rate for ER and PR was lower in India than that reported in Western literature.In the European and American population, 60-80 % patients were found with positive receptor expression.27This may be due to lower average age at diagnosis or racial difference.Triple negative cases were more common in Grade III (9/45) compared to grade II (4/45) and grade I (3/45).One of the reasons for triple negative grade I and II carcinomas in our study was due to the analysis of biomarkers in CNB.ER+/PR+ and HER-2/neu negative status were most common in grade I (4/45) and grade II (7/45) carcinoma.The grade of tumors in the present study correlated to the expression of ER, PR as well as HER-2neu status.As shown by the other studies25