Nafissi N, Makhdoom A, Hoseini M, Akbari M. E, Hashemi M, Sarafzadeh A, Negahi A. Investigating the Health of Resection Margins for Conducting Intra-operative During Breast Conservative Surgery. Biomed Pharmacol J 2016;9(2).

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Manuscript received on :May 25, 2016
Manuscript accepted on :July 05, 2016
Published online on: --

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Nahid Nafissi^1,2, Amir Makhdoom¹, Mostafa Hoseini¹, Mohammad Esmaeil Akbari², Mohammad Hashemi^2,3, Alireza Sarafzadeh⁴ and Alireza Negahi^1*

¹Department of Surgery , Iran University of Medical Science , Teharn , Iran.

²Cancer Research Center, Shahid Beheshti University of Medical , Science , Teharn , Iran.

³Department of Pathology , Shahid Beheshti University of Medical , Science , Teharn , Iran.

⁴Department of Pathology, Khatam-Al Anbia Hospital , Shahid Beheshti University of Medical , Science , Teharn , Iran.

*Corresponding author E-mail : arnegahi@gmail.com  

DOI : https://dx.doi.org/10.13005/bpj/1001

Abstract

To conduct radiotherapy during operation in treating the breast cancer through breast conservative surgery method, we must ensure the healthiness of resection margins during the operation. Then, electron ray is flashed to the surrounding tissues in order to reduce the chance of the presence of any microscopic cancer cells. The present research studies the ability of Frozen in diagnosing the health or involvement of margins during the operation and seeks to compare the results of Frozen with the results of gold standard (permanent pathology) diagnostic method in patients suffering from breast cancer who have undergone breast conservative surgery and Intra-operative radiotherapy. In this observational study conducted in the form of a retrospective research, some 496 patients suffering from breast cancer who have undergone breast conservative surgery were selected through the convenience sampling method and the results of breast margin pathologies conducted through Permanent and Frozen methods were compared against one another so that we may find the sensitivities and specifications of the Frozen methods in comparison with the Permanent method. In the Frozen and Permanent methods, the margins had a freedom degree of 83.1% and 98% respectively. The sensitivity and peculiarity of the Frozen method as compared to the Permanent method were 80% and 84% respectively, however the negative predictive value was 99.5%. A significant relationship was observed here based on chi square test. The level of accuracy was 84.3%, and the pseudo negative weas 0.5%. The compliance level of the Permanent and Frozen diagnostic methods was 84.3%. It is therefore concluded that the Frozen method has a good degree of compliance in determining the state of margin of the removed cancerous lump in breast conservative surgeries and false negative reports have been issued for 0.5% of the cases. Thus, it is recommended to use the Frozen method before radiotherapy to determine the freedom of margins.

Keywords

Breast Conservative Surgery and Intra-operative radiotherapy; Frozen Method; Permanent Method

Introduction

The breast cancer is one of the most common types of cancer observed among the Iranian women. In 70% of the cases, this cancer is diagnosed only after it has reached the advanced or the metastatic state. In 50% of the cases, this cancer is diagnosed only when its size has exceeded 5 cm (1-2). Thanks to the awareness of the patients, this disease is usually diagnosed in its early stages and only 45.5% of them are diagnosed when they have reached the advanced level (3). The 5-year perseverance level of this disease in Iran is 62% which is slightly more than what is observed in other countries (4). Those afflicted with this cancer will experience deterioration of their life quality due to its physical side effects and other psycho-mental problems (5-6). Today, various methods are used to diagnose breast cancer each one being of certain accuracy. Such methods include pre-surgery biopsy, sampling and pathologic examination during the surgery using Frozen and Permanent methods (7-9). Examining the Permanent pathology samples taken during breast surgery is considered to be the main method. Utilizing a method with the same degree of precision during the operation for diagnosing the involvement of margins can be of great help for conducting Intra-operative during the breast conservative surgery and reduce treatment costs and side effects of re-surgery (10, 11). The first step will be the measurement of diagnosis precision and the compliance level of the Frozen method in comparison with the Permanent method about the margins of the breast that is under surgery. The present research has studied the compliance level of the pathology results of breast margin in Permanent and Frozen methods on those afflicted with breast cancer who have undergone breast conservative surgery.

Patient and Methods

In this research conducted as a diagnostic study, 496 patients with breast cancer in Khatam Al Anbiya Hospital who had undergone breast conservative surgery were selected through convenience sampling method. The results of breast margin pathologies through both Permanent and Frozen methods were compared against one another so that we may learn about the sensitivity and peculiarity of the Frozen method in comparison with its Permanent counterpart. SPSS version 13 was utilized to analyze the collected data. Frequency and frequency percentage were calculated for the qualitative data, while mean and standard deviation were calculated for the quantitative data. Chi square and Fisher tests were used and the significance level for the interpretation of the results was 0.05. Furthermore, the sensitivity and peculiarity of the Frozen method in comparison to its Permanent counterpart and the Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for the patients were also measured.

Results

The average age of the 496 participants studied was 50.4, the average number of positive lymph nodes was 2 and the average size of tumor was 21.5 mm. The following frequencies were reported for different tumors: 5.2% for DCIS, 72.8% for IDC, 11.9% for ILC, 6.9% for Mixed type and 3.2% for other types of tumors. The following grades were also reported for tumors: 1 for 10.25% of the cases, 2 for 60% of the cases, and 3 for 29.75% of the cases. Perineural invasion was observed in 21.6% of the cases. Vascular invasion of tumor was observed in 38.9% of the cases. 21.4% of the tumors had calcification. 30.8% of the tumors had necrosis. 46.4% of the involvements were observed on the right hand-side, 46.8% were observed on the left hand-side, and 0.4% was bilateral. Family history was positive in 9.5% of the cases. The estrogen receptor was positive in 69.7% of the cases. The progesterone receptor was positive in 69.9% of the cases. HER2 receptor was positive in 19.1% of the cases. In the Frozen state, the margin was free in 83.1% of the cases. However in the Permanent state, the margin was free in 98% of the cases. The sensitivity and specificity of the Frozen method as compared to the Permanent method were 80% and 84% respectively, however the negative and positive predictive values were 99.5% and 9.5% respectively. A significant relationship was observed here based on Chi square test. The level of accuracy was 84.3%, and the pseudo negative and pseudo positive were 0.5% and 90.5% respectively. The compliance level of the Permanent and Frozen diagnostic methods was 84.3%. The 2 cases (0.5%) which were pseudo-negative were finally diagnosed as ductal carcinoma insitu tumors (DCIS) . The negative state of estrogen receptor was accompanied by higher levels of sensitivity and specificity. The negative state of progesterone receptor was accompanied by higher levels of sensitivity and specificity. The positive state of HER2 receptor was accompanied by higher levels of sensitivity; but it had no influence over specificity. The pathologic type of the tumor had no influence on the sensitivity and specificity of the Frozen. As the grade of tumor increases, we witnessed in rise in sensitivity and a reduction in specificity. In the cases where we had Perineural invasion, we observed higher levels of sensitivity but the specificity remained unaffected. Higher levels of sensitivity were recorded in the cases of vascular invasion, but no difference was observed for specificity. Higher levels of sensitivity were recorded in the cases of calcification, but lower levels of specificity were observed. Higher levels of sensitivity were recorded in the cases of necrosis, but lower levels of specificity were observed. Family history had no impact on specificity and sensitivity.

Discussion

In the Frozen and Permanent methods, the margins had a freedom degree of 83.1% and 98% respectively. This means that 16.9% of the margins were positive during the first surgery and if Intra-operative is conducted without checking the margin, this percentage of the patients whould not benefit from anything. The sensitivity and specificity of the Frozen method as compared to the Permanent method were 80% and 84% respectively, however the negative and positive predictive values were 99.5% and 9.5%. A significant correlation was observed here based on Chi square test. This means that Frozen was wrong only among 0.5% of the patients and this error has probably been due to the engagement between Margin and DCIS centers. No need for a new surgery after the removal of the margin was reported and the percentage of a successful surgery reached zero.

Another study conducted by Nafissi et al. in Iran whose results were published in 2012, 237 people were studied and based on the study of Frozen, margin was positive in 25% of the cases all of whom underwent Re-Excision in the very same session. As for Permanent, margin was positive in 2.9% of them which shows using Frozen prevented re-surgery in 23% of the patients. In this study, the sensitivity of Frozen in diagnosing the malignant cases in breast margin was 100%, while its specificity was 99.2% (12). In another study conducted by Tan et al in Singapore whose results were published in 2014, 161 patients who had undergone breast surgery were studied. The results showed non-compliance in terms of Frozen and Permanent results among 4 patients (pseudo positive) and no case of pseudo negative which needed re-operation was recorded. There was non-compliance between the results of Frozen and Permanent in 98.4% of the cases (13). In another study conducted by Jorns et al in U.S.A whose results were published in 2012, 181 patients were studied. They were compared with 188 people who had undergone the Permanent method without Frozen. The results showed that conducting Frozen has resulted in decreased need for Re-excision in 34% of the patients, while this level in our study was only 9.5% (real positive Frozen) which is well below the level reported in this research (14). In another study conducted by Dener et al. in Turkey whose results were published in 2009, 186 patients were studied using Frozen Section method. The results indicated the need for Re-excision in 16% of the cases and only 2.1% of the patients experienced local recurrence (15). In another study conducted by Weber et al in Switzerland whose results were published in 2008, 80 patients were studied using the Frozen method and it was announced that the diagnosis precision and sensitivity and specificity of this method were 83.8%, 80% and 87.5% respectively (16). In another study conducted by Olsen et al in the US whose results were published in 2009, 290 patients were studied using Frozen Section method and the results showed that 2.7% of the patients required Re-excision (17). In the study conducted by Weber et al in the US whose results were published in 1997, 169 patients were studied using Frozen Section method and the results showed that 15% of the patients required Re-excision and the sensitivity and specificity levels of the Frozen method were 91% and 100% respectively (18). In another study conducted by Noguchi et al. (1995) in Japan, 95 patients were studied using Frozen method and the diagnostic precision of this method in comparison with the Permanent method was recorded to be 87%, while its sensitivity and specificity were 96% and 84% respectively (19).

Conclusion

Based on all evidences presented in this research, we may conclude that Frozen method exhibits a good level of compliance in determining the state of the margin of the tumor removed in breast conservative surgery before conducting intra-operative radiotherapy. Thus, utilizing the frozen method is recommended.

Finally, multi-center studies with larger samples are recommended so that more generalizable results may be achieved.

References

1. Harirchi I, Ebrahimi M, Zamani N, Jarvandi S, Montazeri A. Breast cancer in Iran: a review of 903 case records. Public Health. 2000; 114(2):143-5.
2. Alizadeh Otaghvar H, Hosseini M, Tizmaghz A, Shabestanipour G, Noori H. A review on metastatic breast cancer in Iran. Asian Pac J Trop Biomed 2015; 5(6): 429–433
3. Akbari ME, Khayamzadeh M, Khoshnevis SJ, Nafisi N, Akbari A. Five and Ten Years Survival in Breast Cancer Patients Mastectomies vs. Breast Conserving Surgeries Personal Experience. IJCP, Vol 1, No 2, April 2008 p:53-56.
4. Vahdaninia M, Montazeri A. Breast cancer in Iran: a survival analysis. Asian Pac J Cancer Prev. 2004 Apr-Jun;5(2):223-5.
5. Hosseini M, Tizmaghz A, Alizadeh Otaghvar H, Shams M. The Prevalence of Fibrocystic changes of breast tissue of patients who underwent reduction mammoplasty in Rasool-Akram, Firuzgar and Sadr Hospitals during 2007–2012. Adv Surg Sci 2014; 2(1): 5-8.
6. Radice D, Redaelli A. Breast cancer management: quality-of-life and cost considerations. 2003;21(6):383-96.
7. Köchli OR. Developments in minimally invasive breast surgery – overview and our own experience: new diagnostic and therapeutic challenges in breast cancer. Gynakol Geburtshilfliche Rundsch. 2000;40(1):3-12.
8. Komaki K, Sakamoto G, Sugano H, et al. The accuracy of frozen sections in the diagnoses of breast lesions. Gan No Rinsho. 1986 Jan;Suppl:238-47.
9. Simsir A, Waisman J, Thorner K, Cangiarella J. Mammary lesions diagnosed as “papillary” by aspiration biopsy: 70 cases with follow-up. 2003 Jun 25;99(3):156-65.
10. Weinberg E, Cox C, Dupont E, et al. Local recurrence in lumpectomy patients after imprint cytology margin evaluation. Am J Surg. 2004 Oct;188(4):349-54.
11. Cox CE, Hyacinthe M, Gonzalez RJ, et al. Cytologic evaluation of lumpectomy margins in patients with ductal carcinoma in situ: clinical outcome. Ann Surg Oncol. 1997 Dec;4(8):644-9.
12. Nafissi N, Khayamzadeh M, Sarafzadeh A, et al. Accuracy of Intraoperative Margin Investigation by Frozen-Section in Breast Conservative Surgery. Basic Clin Cancer Res North Am. 4, Feb. 2012. Available at:http://www.bccrjournal.com. Date accessed: 5 Aug. 2015.
13. Tan MP, Sitoh NY, Sim AS. The value of intraoperative frozen section analysis for margin status in breast conservation surgery in a nontertiary institution. Int J Breast Cancer. 2014;2014:715404.
14. Jorns JM, Visscher D, Sabel M, et al. Intraoperative frozen section analysis of margins in breast conserving surgery significantly decreases reoperative rates: one-year experience at an ambulatory surgical center. Am J Clin Pathol. 2012 Nov;138(5):657-69.
15. Dener C, Inan A, Sen M, Demirci S. Interoperative frozen section for margin assessment in breast conserving energy. Scand J Surg. 2009;98(1):34-40.
16. Weber WP, Engelberger S, Viehl CT, et al. Accuracy of frozen section analysis versus specimen radiography during breast-conserving surgery for nonpalpable lesions. World J Surg. 2008 Dec;32(12):2599-606.
17. Olson TP, Harter J, Muñoz A, Mahvi DM, Breslin T. Frozen section analysis for intraoperative margin assessment during breast-conserving surgery results in low rates of re-excision and local recurrence. Ann Surg Oncol. 2007 Oct;14(10):2953-60.
18. Weber S, Storm FK, Stitt J, Mahvi DM. The role of frozen section analysis of margins during breast conservation surgery. Cancer J Sci Am. 1997 Sep-Oct;3(5):273-7.
19. Noguchi M, Minami M, Earashi M, Taniya T, Miyazaki I, Mizukami Y, Nonomura A. Intraoperative histologic assessment of surgical margins and lymph node metastasis in breast-conserving surgery. J Surg Oncol. 1995 Nov;60(3):185-90.
20. Isaacs AJ, Gemignani ML, Pusic A, Sedrakyan A. Association of Breast Conservation Surgery for Cancer With 90-Day Reoperation Rates in New York State. JAMA Surg. 2016 Feb 17. doi: 10.1001/jamasurg.2015.5535.