Concordance Between Frozen Section and Permanent Section in Assessment of Resection Margins in Breast Conserving Surgery Among Patients with Breast Cancer

Introduction: Breast cancer is considered as one of the most common malignancies among Iranian women and the most common cancer among women worldwide, with an incidence of over one million new cases per year worldwide, and is still the leading cause of morbidity in women with 411,000 cases per annum. The purpose of current study is to evaluate the compliance between samples of Frozen Section and Permanent section with respect to examination of the breast mass margin in breast conserving surgery. Methods and materials: Current study was retrospective cross-sectional study in which, 143 patients with BC were included via convenient sampling method. Our study’s sample was obtained from patients who referred to Shohada Tajrish Hospital (Tehran, Iran) between 2009-2011 and went through breast mass surgery; subsequently, their tissue samples were assessed and reported via frozen section and permanent section methods. Obtained data was assessed via SPSS24 software. Results: Results of Chi-square test reported the chi-square is equal to 126.392 and the degree of freedom (dof)=2, which indicates that the data is three-layered; significance=0.000 confirmed rejection of the null hypothesis and the nonuniformity of the data. Hence, It can be inferred that data are valid and testable. In the t-test, the number of data is 143 and its mean is 1.028, which is the same as the descriptive statistics. However, it differs from the mean of the society, which should be considered our Inferential-test results. Our zero assumption seeks out the same results of both methods. The results of the research are not rejected by the significance of 0.481 above 0.05, and the results can be stated to be the same on average. Conclusion: According to the obtained data, compliance of the Frozen section and the Permanent section in the examination of marginal breast masses in Shohada Tajrish Hospital; two sampling modalities show higher than 77.6% similarity. Furthermore, Frozen section modality tend to be quicker procedure and the results can be delivered to surgeon and in result he may make more accurate therapeutic decisions and this may reduce number of anesthesia and surgical procedures on a patients. Hence, due to high concordance rate between results of Frozen section and permanent section plus competitive advantage of time saving in frozen section approach, this approach may be considered as gold standard approach regarding evaluation of tumoral and non-tumoral masses in the examination of the breast mass margin in breast conserving surgery.


Introduction
Breast cancer (BC) is among the most prevalent noncutaneous malignancies worldwide; BC is ranked as 2 nd most common cancer and the 5 th most prevalent cause of cancer morbidity globally. According to American Cancer Society, roughly around 232,670 women will realize they suffer from BC this year, and around 40,000 of afflicted will die from this malignancy [2]; male BC is responsible for less than 1% of all breast cancers in the United States and with early diagnosis and fitting treatment it maintains high remission rate [5]. Over the past two decades, in Asia, numbers have shown that the incidence of breast cancer has doubled or tripled per annum [3]; this alarming number calls for prevention, early detection and impeccable intervention plans. Various factors have been attributed to etiology of BC such as family history [6], significant inherited predisposition [7,8], breast morphology [9], reproductive, and hormonal factors, hormonal therapy, obesity and alcohol drinking [10][11][12]. Fortunately, there exists some protective factors and therapeutic plan to alleviate risk of BC among women such as Estrogen therapy after hysterectomy [13,14,15], physical training [16], early pregnancy [17], breast feeding [17], Selective estrogen receptor modulators (SERMs) [18], Aromatase inhibitors or inactivators [19], Risk decreasing mastectomy [20], Risk-reducing oophorectomy or ovarian ablation [21]. Screening tend to be vital with respect to diagnosis and early intervention in BC; some clinicians believe that breast self-examination can be useful approach; however efficacy of this method regarding reducing morbidity number has not scientifically been proved [22]; MRI, ultrasound, biopsy and blood chemistry evaluation are also commonly used with respect to BC detection, Mammography however, is considered as the backbone in breast cancer detection [23].
Various BC treatment approaches have been offered so far such as surgery, radiation therapy, chemotherapy, hormone therapy, targeted therapy [24].
Various surgery approaches have been offered so far depending on type, progression and characteristic of breast carcinoma such as Breast Conserving Surgery (BCS), Total Mastectomy (TM) and Modified Radical Mastectomy (MRM).
In BCS, surgeon tends to remove cancerous cells and some of the normal tissues around malignant part, however the whole breast remains [24]. Pathologists assess the tissue and accordingly they report to surgeon regarding characteristic of sample, subsequently the surgeon removes the tumor via BCS, TM or MRM. Hence, pathologist's reports play a vital role in decision making of surgeons and possible treatment plans and impeccable and quick assessment of characteristics of BCS would enable both patient and clinician to reach optimum result.
The purpose of current study is to evaluate the results' concordance between samples of Frozen Section and Permanent Section with respect to examination of the breast mass margin in BCS.

Materials and Methods
Current study was retrospective cross-sectional study in which, 143 patients with BC were included via convenient sampling method. Our study's sample was obtained from patients who referred to Shohada Tajrish Hospital (Tehran, Iran) between 2009-2011 and went through breast mass surgery; subsequently, their tissue samples were assessed and reported via frozen section and permanent section methods. While assessing patients' history files some of the samples were excluded because margin masses were not assessed and only type of the cancer was mentioned in their history.
I. Histopathology Assessment: Frozen Section Procedure: Throughout the frozen section process, the surgeon removes part of the tissue mass. Subsequently, the mass biopsy is handed to a pathologist. Via cryostat device, the pathologist freezes the tissue, cuts it with a microtome, and then stains it with various dyes in order to assess the sample via microscopes. The whole process takes less than 20 minutes. Frozen section approach have some advantages: a. If more amount of tissue is needed, it can be provided by surgeons during a surgery without a need for further surgeries b. If the results of frozen section confirms carcinoma in tissue, the mass can be removed at that time c. If the mass founded to be benign, then the surgery can be terminated d. This method can confirm that whole mass and it margins are removed [25]. II. Permanent Section Assessment: Standardized protocols, which are gold standard method for the evaluation of tumoral and non-tumoral masses; the results of this approach is ready few days after a surgery and this long interval can be considered as Achilles hill of this modality.
Results obtained from frozen section procedure and permanent section procedure were compared and recorded. Obtained data was assessed via SPSS-24 software.

Results
One hundred forty three BC patients undergone BCS included in current study. Descriptive statistics of sample tissues obtained from patients is illustrated in Table 1. We specified three codes with respect to concordance status between frozen section and permanent section approaches. 0 = Discordance of two approaches 1 = Concordance of two approaches 2 = Results cannot be assessed According to our obtained data, compliance of the Frozen section and the Permanent section in the examination of marginal breast masses, two sampling modalities have more than 77.6% similarity. Results of Chi-square test reported the chi-square is equal to 126.392 and the degree of freedom (dof) =2, which indicates that the data is three-layered; significance=0.000 confirmed rejection of the null hypothesis and the non-uniformity of the data. Hence, It can be inferred that data are valid and testable. In the t-test, the number of data is 143 and its mean is 1.028, which is the same as the descriptive statistics. However, it differs from the mean of the society (with the number 1), which should be considered our Inferential-test results. Our zero assumption seeks out the same results of both methods. The results of the research are not rejected by the significance of 0.481 above 0.05, and the results can be stated to be the same on average. Finally, according to Likelihood Ratio test, results can be generalized and occurring discordant results in society is low.

Discussion
Considering mushrooming trend and alarming morbidity of breast cancer among Iranian women it seems vital to optimize diagnosis-treatment curve of this malady. Most women prefer to maintain their breast structure and using frozen section approach serve this preference via enabling surgeons to remove malignant mass intraoperative and would hinder unnecessary future invasive surgical procedures. Aforementioned concerns made us to conduct current study in order to evaluate the concordance between samples of Frozen Section and Permanent section with respect to examination of the breast mass margin in breast conserving surgery.
Various studies have discussed efficient role of frozen section modality in intraoperative setting during breast cancer surgery. In consistent with the result of current study, Mona and Colleagues (2014) postulated that frozen section analysis is a reliable modality with respect to Margin Status in Breast Conservation Surgery [26]. In another study conducted by Seung et al. (2017), they postulated that Frozen section analysis of lumpectomy margins during BCS is useful in evaluating lumpectomy margins and preventing reoperation [27].
In various studies accuracy of frozen section analysis is roughly between 78-80% and this number is highly depends on pathologist's experience. However some other factors such as technical errors such as tissue section folds or uneven staining, may preclude proper evaluation [28,29].
Various studies discuss advantages of frozen section in the intraoperative margin assessment during breast surgery. For instance, according to Anila and Colleagues (2016), Intraoperative FSA allows resection of suspicious margins at the time of primary conservative surgery and results in low rates of local recurrence and second surgeries [30].
All in all, our study's result confirms the results in former literatures. According to results of current study there is high concordance between results of frozen section analysis and permanent section in evaluating breast margin during breast conserving surgery. Apart from high accuracy of frozen section modality, obtaining analysis results in short time is considered as competitive advantage of frozen section over permanent section approach. Although, permanent section is considered as gold standard modality regarding histopathology assessment of cancerous tissue in breast cancer, long period for analysis of the results has weakened this approach. Frozen section procedure can be conducted intraoperative in few minutes and the results would enable the surgeon to decide on optimum treatment plan and it would alleviate number of future invasive treatment.

Limitation
This is study was retrospective cross-sectional study. It is advisable to conduct a study only with frozen section analysis; screen group of patients in period of time and see if risk of radical mastectomy, or recurrent surgery have reduced among this group or not.

Conflict of Interest
The authors declare that they have no competing interests.