Sentinel Lymph Node Approach in HER2-Positive and Triple-Negative Breast Cancer with cN0 Status Prior to Neoadjuvant Chemotherapy: Frozen Section or Paraffin Section?

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Ferit Aydin, Kazım Caglar Ozcelik, Emre Tunc, Fatih Aslan, Mahmut Onur Kulturoglu, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7900010/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Axillary management in breast cancer has shifted significantly with the increasing use of neoadjuvant chemotherapy (NACT), particularly in biologically aggressive subtypes such as HER2-positive breast cancer and triple-negative breast cancer (TNBC). Intraoperative frozen section evaluation of sentinel lymph nodes (SLNs) has traditionally guided axillary dissection, but recent evidence suggests that omitting axillary dissection in patients with minimal or no residual disease provides comparable local control when combined with axillary radiotherapy. This study aimed to evaluate whether intraoperative frozen section or paraffin section assessment affects axillary management in patients who are clinically node negative (cN0) before NACT. Methods This retrospective study included 83 patients with HER2-positive breast cancer or TNBC treated between 2023 and 2025. All patients were clinically and radiologically node negative prior to NACT. SLN biopsy was performed using isosulfan blue, dual technique, indocyanine green, or combinations. Intraoperative frozen section analysis was performed in 59 patients, while paraffin section was used in 24 patients. Clinicopathological features, SLN positivity, pathological response rates, axillary recurrence, and surgical decisions were compared. Statistical analyses were performed using SPSS 18.0, with p < 0.05 considered significant. Results The mean age was 48.2 years. A pathological complete response (pCR) was achieved in 71% of patients, of whom 96.6% had negative SLNs. Among patients with partial response, 75% had negative SLNs. SLN positivity was observed in 8.5% (n = 5) of patients in the frozen section group and 12.5% (n = 3) in the paraffin section group. Axillary dissection was performed only in the frozen section group. No axillary recurrences occurred in either group after a median follow-up of 22 months. Paraffin section evaluation did not result in delayed treatment or increased recurrence. Conclusion In HER2-positive and TNBC patients with cN0 status before NACT and a good pathological response, frozen section analysis of SLNs does not influence surgical decision-making. Paraffin section evaluation represents a safe alternative, reducing operative time, anesthesia exposure, and healthcare costs. These findings support axillary de-escalation in selected high-response subgroups. Breast cancer Sentinel lymph node biopsy Neoadjuvant chemotherapy Frozen section Paraffin section HER2-positive Triple-negative breast cancer Axillary surgery De-escalation Introduction Surgical management of the axilla in breast cancer has evolved substantially following the introduction of neoadjuvant chemotherapy (NACT). Although the detection of lymph node metastasis—or even isolated tumor cells using frozen sections after NACT was once considered an indication for axillary dissection, current evidence demonstrates that omitting axillary dissection in patients with minimal residual disease yields comparable rates of axillary recurrence when combined with axillary radiotherapy [ 1 ].This finding implies that intraoperative frozen section evaluation of sentinel lymph nodes (SLNs) may not alter surgical decision-making in selected patients. In particular, for patients who are clinically node negative (cN0) prior to NACT and remain without clinical or radiologic suspicion of axillary involvement after treatment, the utility of frozen section analysis is limited, as it does not significantly influence the surgical approach. Furthermore, awaiting intraoperative pathology results prolongs operative time and anesthesia exposure, increases healthcare costs, and adds to the surgical workload [ 2 ]. In this study, we investigated whether intraoperative frozen section or paraffin section assessment of SLNs affects the decision of axillary dissection in patients with biologically aggressive tumors, such as HER2-positive breast cancer and triple-negative breast cancer (TNBC), who were clinically node-negative (cN0) prior to NACT. We also aimed to identify the subgroup of patients in whom SLN biopsy could safely be evaluated with paraffin section instead of frozen section. Materials and Methods Data from 83 patients with HER2-positive breast cancer or TNBC treated between 2023 and 2025 were retrospectively analyzed. Eligible patients were cN0 upon physical examination; those who were cN0 but had suspicious lymph nodes upon imaging with biopsy-proven benign cytology results were also included. Patients who were clinically node-positive (cN+) before NACT or who had biopsy-proven malignant lymph nodes upon imaging were excluded. Prior to NACT, all patients underwent axillary evaluation with ultrasonography and positron emission tomography. Treatment decisions were made by a multidisciplinary tumor board including medical oncology, surgical oncology and radiation oncology specialists. The therapeutic regimen consisted of an adriamycin–taxane-based neoadjuvant chemotherapy protocol, with dual HER2 blockade added for patients with HER2-positive breast cancer. Following NACT, all patients underwent another axillary evaluation with ultrasonography. SLN mapping was performed using isosulfan blue dye (Lymphazurin™, Covidien, Mansfield, MA, USA), dual technique with gamma probe (Neoprobe Gamma Detection System, Devicor Medical Products, Cincinnati, OH, USA), indocyanine green (ICG, Daiichi Sankyo, Tokyo, Japan), or a combination of these methods. Frozen section analysis was performed on SLNs in 59 patients, and paraffin section evaluation was performed for 24 patients. The decision to perform frozen versus paraffin section was based on intraoperative availability and institutional practice patterns; frozen section was preferred when immediate intraoperative decision-making regarding axillary dissection was required, while paraffin section was used when intraoperative pathology support was unavailable. All pathological evaluations were performed by board-certified breast pathologists with at least 5 years of experience, and the same pathology team evaluated both frozen and paraffin sections to ensure consistency. Final pathology results were compared, and the outcomes of patients who underwent axillary dissection due to SLN positivity were recorded. In patients with HER2-positive disease who achieved a pathologic complete response, HER2 blockade therapy was continued to complete one year. Those with a partial response received trastuzumab emtansine (T-DM1). In the paraffin follow-up group, patients with lymph node metastasis detected in the final pathology were treated with axillary radiotherapy. Patients were followed every 3 months for the first two years and every 6 months thereafter, with routine complete blood count, tumor markers, and breast and axillary ultrasonography. All data were statistically analyzed using SPSS Statistics for Windows, Version 18.0 (SPSS Inc., Chicago, IL, USA). As this was a retrospective study including all eligible patients treated within the study period, no formal sample size calculation was performed. Continuous variables were tested for normality using the Shapiro–Wilk test. Normally distributed data were compared using the Student’s t-test, while non-normally distributed data were analyzed with the Mann–Whitney U test. Categorical variables were compared using the Chi-square test or Fisher’s exact test, as appropriate. A p-value < 0.05 was considered statistically significant. Results The mean patient age was 48.2 years (range: 32–69 years). The mean clinical tumor size was 25.3 mm (range: 10–58 mm), with 24 (28.9%), 55 (66.3%), and 4 (4.8%) patients having T1, T2, and T3 tumors, respectively. Moreover, 39 patients (47.0%) were hormone receptor–positive HER2-positive, 25 (30.1%) were hormone receptor–negative HER2-positive, and 19 (22.9%) had TNBC. On pre-NACT ultrasonography, 85.5% of patients had reactive lymph nodes, and 14.5% (n = 12) had suspicious nodes, with benign cytology confirmed with fine-needle aspiration biopsy. Following NACT, 59 patients (71%) achieved a pathological complete response (pCR) in the primary tumor, and among these, 57 patients (96.6%) had no sentinel lymph node metastasis. Among the 24 patients with a partial response, 18 patients (75%) had negative SLNs. The correlation between pCR and negative SLNs was significant (p < 0.05) (Table 1 ). Table 1 Correlation between clinical response to neoadjuvant chemotherapy and sentinel lymph node biopsy results Clinical Response to NACT Intraoperative Pathological Examination SLNB Result Count % within intraoperative examination Total Partial response Performed Negative 14 73.7% Positive 5 26.3% Total 19 100.0% 19 Not performed Negative 4 80.0% Positive 1 20.0% Total 5 100.0% 5 Overall Total 24 100.0% 24 Complete response Performed Negative 40 95.2% Positive 2 4.8% Total 42 100.0% 42 Not performed Negative 17 100.0% Positive 0 0.0% Total 17 100.0% 17 Overall Total 59 100.0% 59 Breast-conserving surgery was performed in 62 patients (74.7%) of patients, whereas 12 patients (14.5%) underwent simple mastectomy. In addition, five patients with BRCA mutations underwent bilateral nipple-sparing mastectomy with silicone implant reconstruction, and four patients underwent unilateral nipple-sparing mastectomy with silicone implant reconstruction. SLN biopsy was performed using isosulfan blue dye alone in 48.2% of patients, combined techniques in 41%, indocynanine green in two patients, and the dual method alone in 7seven patients. The mean number of dissected SLNs was 4 (range: 2–7). Frozen section analysis was performed in 59 patients (71.1%), whereas paraffin section analysis was performed in 24 (28.9%). The clinical and histopathological features of both groups were comparable (Table 2 ). Table 2 Clinicopathological characteristics of patients according to the method of sentinel lymph node evaluation. Frozen Section % (n = 59) Paraffin Section % (n = 24) p-value Age < 45 years 45.8% (27) 33.3% (8) 0.33 ≥ 45 years 54.2% (32) 66.7% (16) Hormone receptor status HR-positive / HER2+ 45.8% (27) 50.0% (12) 0.44 HER2+ 33.9% (20) 20.8% (5) TNBC 20.3% (12) 29.2% (7) Pre-NACT USG Reactive 88.1% (52) 79.2% (19) 0.31 Suspicious 11.9% (7) 20.8% (5) Post-NACT USG Reactive 96.6% (57) 95.8% (23) 1.00 Suspicious 3.4% (2) 4.2% (1) Response to NACT Complete response 69.5% (41) 75.0% (18) 0.82 Partial response 30.5% (18) 25.0% (6) SLN, sentinel lymph node; NACT, neoadjuvant chemotherapy; TNBC, triple-negative breast cancer. In the paraffin section group, the mean number of dissected SLNs was 4 (range: 2–7). None of the patients had grossly metastatic lymph nodes intraoperatively. Final pathology revealed a single metastatic lymph node in only three patients (12.5%); however, complete axillary dissection was not performed. During a mean follow-up of 22 months, no axillary recurrences were observed in this group. In the frozen section group, the mean number of dissected SLNs was also 4 (range: 2–8). Lymph node metastasis was detected in five patients (8.5%), who subsequently underwent axillary dissection, which yielded a mean of 13 (range: 10–18) nodes. Pathologically, metastasis was detected in a single non-SLN in one patient. During a mean follow-up of 22 months, no axillary recurrences were observed in this group. Discussion Pre-NACT clinical lymph node status remains critical in determining the surgical management of the axilla. Landmark trials, such as ACOSOG Z1071 and SENTINA, have demonstrated that in patients with initially node-positive (cN+) disease who achieved a good response to NACT, SLN biopsy could safely replace axillary dissection, thereby altering the surgical approach to the axilla [ 3 , 4 ]. However, these studies recommended axillary dissection when isolated tumor cells or micrometastases were present in the SLN. Subsequent studies have challenged this approach, concluding that performing only SLN biopsy and avoiding axillary dissection in patients with a good response to NACT and residual metastatic lymph nodes can yield comparable oncologic outcomes when axillary radiotherapy is administered. The OPBC-05/ICARO study reported that patients with isolated tumor cells detected in the SLN after NACT had similar recurrence rates whether treated with axillary dissection or axillary radiotherapy alone [ 5 ]. Similarly, the combined analysis of Neosenti-Turk MF-18-02/18 − 03 revealed that in patients with cN1–2 disease prior to NACT, axillary radiotherapy without axillary dissection achieved comparable results not only in cases with isolated tumor cells/micrometastases but also in those with macrometastases [ 6 ]. Müslümanoğlu et al. observed that SLN biopsy combined with axillary radiotherapy was sufficient in patients with cN1 disease with good pathological response (> 50% fibrosis) and < 3 positive lymph nodes, instead of performing axillary dissection [ 1 ]. Notably, these studies assessed SLNs using intraoperative frozen section; however, the frozen results did not alter surgical decision-making. This raises the question of whether paraffin section evaluation may be adequate in certain patient groups. In patients with TNBC and HER2-positive breast cancer, the rate of pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) is approximately 40%–50%. In this patient population, pCR rates are higher compared to those with luminal A and B subtypes [ 7 , 8 ]. Furthermore, NACT is also effective in eradicating lymph node metastases [ 9 – 11 ]. When pCR is achieved in the primary tumor, negative axillary nodes or axillary pCR is expected. In a study conducted at MD Anderson, of 290 cN0 patients with HER2-positive breast cancer or TNBC, 40.4% achieved pCR in the breast, and none of these patients had axillary metastasis [ 12 ]. In the same study, among 237 biopsy-proven cN + patients, pCR was achieved in the breast in 77 patients, of which 89.6% had no residual axillary metastasis. Furthermore, of 160 patients without breast pCR, 42.5% were free of axillary metastasis. In our study, among patients who were cN0 before NACT, 71% achieved pCR in the primary tumor, of whom 96.6% had negative SLNs. Even among patients with partial response, 75% had negative SLNs. These findings suggest that in patients with HER2-positive breast cancer and TNBC who are cN0 before NACT, and in this subgroup, paraffin section evaluation may safely replace intraoperative frozen section for SLN evaluation. Our findings are supported by a database study of patients with 6802 cN0 HER2-positive breast cancer and 6222 cN0 TNBC with pCR rates of 45% and 37%, respectively. In patients achieving pCR, the rate of axillary metastasis after NACT was only 1.6% in both subgroups, implying that axillary surgery could be avoided for these patients [ 13 ]. Despite these findings, variations in axillary management persist among surgeons. A national survey of 101 surgeons in Türkiye revealed that 76% always performed intraoperative frozen section, whereas only 5% did not [ 14 ]. Notably, 46.5% of surgeons did not perform axillary dissection in cN0 patients when 2–3 SLNs were retrieved and ≤ 2 nodes harbored micrometastases or macrometastases. For these surgeons, frozen section analysis of SLNs did not influence their surgical decision-making. Conclusion In patients with HER2-positive breast cancer and TNBC who are clinically and radiologically node negative prior to NACT, and who achieve a good pathological response in the primary tumor, intraoperative frozen section analysis of SLNs does not alter surgical management. In this subgroup, paraffin section evaluation can be safely performed, thereby avoiding prolonged operative time and unnecessary anesthesia exposure and decreasing healthcare costs. Our findings support the growing evidence that axillary surgery can be deescalated in biologically aggressive subtypes when an excellent response to systemic therapy is achieved. Future prospective multicenter trials should validate the omission of frozen sections in this setting and define standardized criteria for selecting patients who may safely undergo paraffin section evaluation alone. Declarations Ethics approval and consent to participate: The study was approved by the Ethics Committee of Ankara Etlik City Hospital (Approval No: AEŞ-BADEK2-2025-157). Informed consent to participate was obtained from all participants. This study was conducted in accordance with the principles of the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests. Funding: This research received no external funding. Author Contribution Conceptualization:FA,KCO ; Methodology:FA,KCO,LD ; Data Curation:KCO,ET ; Formal Analysis:FaA,BA; Investigation:MOK,LD; Resources:FA;LD; Writing – Original Draft:KCO,ET; Writing – Review & Editing:ET,BA,LD; Supervision:LD; Project Administration: MOK,FaA Acknowledgements: The authors have no acknowledgments to declare. Clinical trial number : Not applicable. Data Availability The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. References Muslumanoglu M, Mollavelioglu B, Cabioglu N, Emiroglu S, Tukenmez M, Karanlık H, et al. Axillary lymph node dissection is not required for breast cancer patients with minimal axillary residual disease after neoadjuvant chemotherapy. World J Surg Oncol. 2024;22:286. Aydin F, Kulturoglu MO, Aslan F, Dogan L. Intraoperative frozen section analysis can be omitted in early breast cancer without significantly elevating reoperation rates. BMC Surg. 2025;25:347. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14:609–18. Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310:1455–61. Montagna G, Laws A, Ferrucci M, Mrdutt MM, Sun SX, Bademler S, et al. Nodal burden and oncologic outcomes in patients with residual isolated tumor cells after neoadjuvant chemotherapy (ypN0i+): the OPBC-05/ICARO Study. J Clin Oncol. 2025;43:810–20. Muslumanoglu M, Cabioglu N, Igci A, Karanlik H, Kocer HB, Senol K et al. Combined analysis of the MF18-02/MF18-03 NEO-SENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in breast cancer patients with good response to neoadjuvant chemotherapy when radiotherapy is provided. Cancer. 2024;1–14. von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804. Houssami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 2012;48(18):3342–54. Kuerer HM, Sahin AA, Hunt KK, et al. Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999;230(1):72–8. Mougalian SS, Hernandez M, Lei X, et al. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2(4):508–16. Dominici LS, Negron Gonzalez VM, Buzdar AU, et al. Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer. 2010;116(12):2884–9. Tadros AB, Yang WT, Krishnamurthy S, Rauch GM, Smith BD, Valero V, et al. Identification of patients with documented pathologic complete response in the breast after neoadjuvant chemotherapy for omission of axillary surgery. JAMA Surg. 2017;152(7):665–70. Barron AU, Hoskin TL, Day CN, Hwang ES, Kuerer HM, Boughey JC. Association of low nodal positivity rate among patients with ERBB2-positive or triple-negative breast cancer and breast pathologic complete response to neoadjuvant chemotherapy. JAMA Surg. 2018;153(12):1120–6. Cabioglu N, Ercan DO, Karatas I, Eroz E, Toprak S, Emiroğlu S, et al. Changing practice patterns in axillary management for patients with node-positive breast cancer towards increased use of sentinel lymph node biopsy alone after neoadjuvant chemotherapy: results of a survey (MF17-01) among Turkish surgeons. Langenbecks Arch Surg. 2025;410:196. Additional Declarations No competing interests reported. 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08:14:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":554726,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7900010/v1/cc517f33-da3c-4fe1-b9a8-b22a11ce77f5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sentinel Lymph Node Approach in HER2-Positive and Triple-Negative Breast Cancer with cN0 Status Prior to Neoadjuvant Chemotherapy: Frozen Section or Paraffin Section?","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSurgical management of the axilla in breast cancer has evolved substantially following the introduction of neoadjuvant chemotherapy (NACT). Although the detection of lymph node metastasis\u0026mdash;or even isolated tumor cells using frozen sections after NACT was once considered an indication for axillary dissection, current evidence demonstrates that omitting axillary dissection in patients with minimal residual disease yields comparable rates of axillary recurrence when combined with axillary radiotherapy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].This finding implies that intraoperative frozen section evaluation of sentinel lymph nodes (SLNs) may not alter surgical decision-making in selected patients. In particular, for patients who are clinically node negative (cN0) prior to NACT and remain without clinical or radiologic suspicion of axillary involvement after treatment, the utility of frozen section analysis is limited, as it does not significantly influence the surgical approach. Furthermore, awaiting intraoperative pathology results prolongs operative time and anesthesia exposure, increases healthcare costs, and adds to the surgical workload [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this study, we investigated whether intraoperative frozen section or paraffin section assessment of SLNs affects the decision of axillary dissection in patients with biologically aggressive tumors, such as HER2-positive breast cancer and triple-negative breast cancer (TNBC), who were clinically node-negative (cN0) prior to NACT. We also aimed to identify the subgroup of patients in whom SLN biopsy could safely be evaluated with paraffin section instead of frozen section.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eData from 83 patients with HER2-positive breast cancer or TNBC treated between 2023 and 2025 were retrospectively analyzed. Eligible patients were cN0 upon physical examination; those who were cN0 but had suspicious lymph nodes upon imaging with biopsy-proven benign cytology results were also included. Patients who were clinically node-positive (cN+) before NACT or who had biopsy-proven malignant lymph nodes upon imaging were excluded. Prior to NACT, all patients underwent axillary evaluation with ultrasonography and positron emission tomography. Treatment decisions were made by a multidisciplinary tumor board including medical oncology, surgical oncology and radiation oncology specialists. The therapeutic regimen consisted of an adriamycin\u0026ndash;taxane-based neoadjuvant chemotherapy protocol, with dual HER2 blockade added for patients with HER2-positive breast cancer. Following NACT, all patients underwent another axillary evaluation with ultrasonography.\u003c/p\u003e\u003cp\u003eSLN mapping was performed using isosulfan blue dye (Lymphazurin\u0026trade;, Covidien, Mansfield, MA, USA), dual technique with gamma probe (Neoprobe Gamma Detection System, Devicor Medical Products, Cincinnati, OH, USA), indocyanine green (ICG, Daiichi Sankyo, Tokyo, Japan), or a combination of these methods. Frozen section analysis was performed on SLNs in 59 patients, and paraffin section evaluation was performed for 24 patients. The decision to perform frozen versus paraffin section was based on intraoperative availability and institutional practice patterns; frozen section was preferred when immediate intraoperative decision-making regarding axillary dissection was required, while paraffin section was used when intraoperative pathology support was unavailable. All pathological evaluations were performed by board-certified breast pathologists with at least 5 years of experience, and the same pathology team evaluated both frozen and paraffin sections to ensure consistency. Final pathology results were compared, and the outcomes of patients who underwent axillary dissection due to SLN positivity were recorded.\u003c/p\u003e\u003cp\u003eIn patients with HER2-positive disease who achieved a pathologic complete response, HER2 blockade therapy was continued to complete one year. Those with a partial response received trastuzumab emtansine (T-DM1). In the paraffin follow-up group, patients with lymph node metastasis detected in the final pathology were treated with axillary radiotherapy. Patients were followed every 3 months for the first two years and every 6 months thereafter, with routine complete blood count, tumor markers, and breast and axillary ultrasonography.\u003c/p\u003e\u003cp\u003eAll data were statistically analyzed using SPSS Statistics for Windows, Version 18.0 (SPSS Inc., Chicago, IL, USA). As this was a retrospective study including all eligible patients treated within the study period, no formal sample size calculation was performed. Continuous variables were tested for normality using the Shapiro\u0026ndash;Wilk test. Normally distributed data were compared using the Student\u0026rsquo;s t-test, while non-normally distributed data were analyzed with the Mann\u0026ndash;Whitney U test. Categorical variables were compared using the Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean patient age was 48.2 years (range: 32\u0026ndash;69 years). The mean clinical tumor size was 25.3 mm (range: 10\u0026ndash;58 mm), with 24 (28.9%), 55 (66.3%), and 4 (4.8%) patients having T1, T2, and T3 tumors, respectively. Moreover, 39 patients (47.0%) were hormone receptor\u0026ndash;positive HER2-positive, 25 (30.1%) were hormone receptor\u0026ndash;negative HER2-positive, and 19 (22.9%) had TNBC. On pre-NACT ultrasonography, 85.5% of patients had reactive lymph nodes, and 14.5% (n\u0026thinsp;=\u0026thinsp;12) had suspicious nodes, with benign cytology confirmed with fine-needle aspiration biopsy.\u003c/p\u003e\u003cp\u003eFollowing NACT, 59 patients (71%) achieved a pathological complete response (pCR) in the primary tumor, and among these, 57 patients (96.6%) had no sentinel lymph node metastasis. Among the 24 patients with a partial response, 18 patients (75%) had negative SLNs. The correlation between pCR and negative SLNs was significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelation between clinical response to neoadjuvant chemotherapy and sentinel lymph node biopsy results\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical Response to NACT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntraoperative Pathological Examination\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSLNB Result\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCount\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e% within intraoperative examination\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e\u003cp\u003ePartial response\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003ePerformed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e73.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e26.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e100.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eNot performed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e80.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e20.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e100.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall Total\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e100.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e24\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"6\" rowspan=\"7\"\u003e\u003cp\u003eComplete response\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003ePerformed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e95.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e4.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e100.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e42\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eNot performed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e100.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePositive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e100.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e17\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall Total\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e100.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e59\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eBreast-conserving surgery was performed in 62 patients (74.7%) of patients, whereas 12 patients (14.5%) underwent simple mastectomy. In addition, five patients with BRCA mutations underwent bilateral nipple-sparing mastectomy with silicone implant reconstruction, and four patients underwent unilateral nipple-sparing mastectomy with silicone implant reconstruction.\u003c/p\u003e\u003cp\u003eSLN biopsy was performed using isosulfan blue dye alone in 48.2% of patients, combined techniques in 41%, indocynanine green in two patients, and the dual method alone in 7seven patients. The mean number of dissected SLNs was 4 (range: 2\u0026ndash;7). Frozen section analysis was performed in 59 patients (71.1%), whereas paraffin section analysis was performed in 24 (28.9%). The clinical and histopathological features of both groups were comparable (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinicopathological characteristics of patients according to the method of sentinel lymph node evaluation.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFrozen Section % (n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eParaffin Section % (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;45 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e45.8% (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e33.3% (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;45 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e54.2% (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e66.7% (16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHormone receptor status\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHR-positive / HER2+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e45.8% (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e50.0% (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHER2+\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33.9% (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20.8% (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTNBC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20.3% (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e29.2% (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePre-NACT USG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReactive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e88.1% (52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e79.2% (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuspicious\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11.9% (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e20.8% (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePost-NACT USG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReactive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e96.6% (57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e95.8% (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSuspicious\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.4% (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4.2% (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eResponse to NACT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplete response\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e69.5% (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e75.0% (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.82\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePartial response\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e30.5% (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e25.0% (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eSLN, sentinel lymph node; NACT, neoadjuvant chemotherapy; TNBC, triple-negative breast cancer.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eIn the paraffin section group, the mean number of dissected SLNs was 4 (range: 2\u0026ndash;7). None of the patients had grossly metastatic lymph nodes intraoperatively. Final pathology revealed a single metastatic lymph node in only three patients (12.5%); however, complete axillary dissection was not performed. During a mean follow-up of 22 months, no axillary recurrences were observed in this group.\u003c/p\u003e\u003cp\u003eIn the frozen section group, the mean number of dissected SLNs was also 4 (range: 2\u0026ndash;8). Lymph node metastasis was detected in five patients (8.5%), who subsequently underwent axillary dissection, which yielded a mean of 13 (range: 10\u0026ndash;18) nodes. Pathologically, metastasis was detected in a single non-SLN in one patient. During a mean follow-up of 22 months, no axillary recurrences were observed in this group.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePre-NACT clinical lymph node status remains critical in determining the surgical management of the axilla. Landmark trials, such as ACOSOG Z1071 and SENTINA, have demonstrated that in patients with initially node-positive (cN+) disease who achieved a good response to NACT, SLN biopsy could safely replace axillary dissection, thereby altering the surgical approach to the axilla [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, these studies recommended axillary dissection when isolated tumor cells or micrometastases were present in the SLN.\u003c/p\u003e\u003cp\u003eSubsequent studies have challenged this approach, concluding that performing only SLN biopsy and avoiding axillary dissection in patients with a good response to NACT and residual metastatic lymph nodes can yield comparable oncologic outcomes when axillary radiotherapy is administered. The OPBC-05/ICARO study reported that patients with isolated tumor cells detected in the SLN after NACT had similar recurrence rates whether treated with axillary dissection or axillary radiotherapy alone [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Similarly, the combined analysis of Neosenti-Turk MF-18-02/18\u0026thinsp;\u0026minus;\u0026thinsp;03 revealed that in patients with cN1\u0026ndash;2 disease prior to NACT, axillary radiotherapy without axillary dissection achieved comparable results not only in cases with isolated tumor cells/micrometastases but also in those with macrometastases [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. M\u0026uuml;sl\u0026uuml;manoğlu et al. observed that SLN biopsy combined with axillary radiotherapy was sufficient in patients with cN1 disease with good pathological response (\u0026gt;\u0026thinsp;50% fibrosis) and \u0026lt;\u0026thinsp;3 positive lymph nodes, instead of performing axillary dissection [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Notably, these studies assessed SLNs using intraoperative frozen section; however, the frozen results did not alter surgical decision-making. This raises the question of whether paraffin section evaluation may be adequate in certain patient groups.\u003c/p\u003e\u003cp\u003eIn patients with TNBC and HER2-positive breast cancer, the rate of pathological complete response (pCR) following neoadjuvant chemotherapy (NACT) is approximately 40%\u0026ndash;50%. In this patient population, pCR rates are higher compared to those with luminal A and B subtypes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Furthermore, NACT is also effective in eradicating lymph node metastases [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. When pCR is achieved in the primary tumor, negative axillary nodes or axillary pCR is expected. In a study conducted at MD Anderson, of 290 cN0 patients with HER2-positive breast cancer or TNBC, 40.4% achieved pCR in the breast, and none of these patients had axillary metastasis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the same study, among 237 biopsy-proven cN\u0026thinsp;+\u0026thinsp;patients, pCR was achieved in the breast in 77 patients, of which 89.6% had no residual axillary metastasis. Furthermore, of 160 patients without breast pCR, 42.5% were free of axillary metastasis.\u003c/p\u003e\u003cp\u003eIn our study, among patients who were cN0 before NACT, 71% achieved pCR in the primary tumor, of whom 96.6% had negative SLNs. Even among patients with partial response, 75% had negative SLNs. These findings suggest that in patients with HER2-positive breast cancer and TNBC who are cN0 before NACT, and in this subgroup, paraffin section evaluation may safely replace intraoperative frozen section for SLN evaluation. Our findings are supported by a database study of patients with 6802 cN0 HER2-positive breast cancer and 6222 cN0 TNBC with pCR rates of 45% and 37%, respectively. In patients achieving pCR, the rate of axillary metastasis after NACT was only 1.6% in both subgroups, implying that axillary surgery could be avoided for these patients [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDespite these findings, variations in axillary management persist among surgeons. A national survey of 101 surgeons in T\u0026uuml;rkiye revealed that 76% always performed intraoperative frozen section, whereas only 5% did not [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Notably, 46.5% of surgeons did not perform axillary dissection in cN0 patients when 2\u0026ndash;3 SLNs were retrieved and \u0026le;\u0026thinsp;2 nodes harbored micrometastases or macrometastases. For these surgeons, frozen section analysis of SLNs did not influence their surgical decision-making.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn patients with HER2-positive breast cancer and TNBC who are clinically and radiologically node negative prior to NACT, and who achieve a good pathological response in the primary tumor, intraoperative frozen section analysis of SLNs does not alter surgical management. In this subgroup, paraffin section evaluation can be safely performed, thereby avoiding prolonged operative time and unnecessary anesthesia exposure and decreasing healthcare costs.\u003c/p\u003e\u003cp\u003eOur findings support the growing evidence that axillary surgery can be deescalated in biologically aggressive subtypes when an excellent response to systemic therapy is achieved. Future prospective multicenter trials should validate the omission of frozen sections in this setting and define standardized criteria for selecting patients who may safely undergo paraffin section evaluation alone.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003cp\u003e The study was approved by the Ethics Committee of Ankara Etlik City Hospital (Approval No: AEŞ-BADEK2-2025-157). Informed consent to participate was obtained from all participants. This study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003ch2\u003eCompeting interests:\u003c/h2\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThis research received no external funding.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization:FA,KCO ; Methodology:FA,KCO,LD ; Data Curation:KCO,ET ; Formal Analysis:FaA,BA; Investigation:MOK,LD; Resources:FA;LD; Writing \u0026ndash; Original Draft:KCO,ET; Writing \u0026ndash; Review \u0026amp;amp; Editing:ET,BA,LD; Supervision:LD; Project Administration: MOK,FaA\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e\u003cp\u003eThe authors have no acknowledgments to declare.\u003c/p\u003e\u003cp\u003e\u003cb\u003eClinical trial number\u003c/b\u003e: Not applicable.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMuslumanoglu M, Mollavelioglu B, Cabioglu N, Emiroglu S, Tukenmez M, Karanlık H, et al. Axillary lymph node dissection is not required for breast cancer patients with minimal axillary residual disease after neoadjuvant chemotherapy. World J Surg Oncol. 2024;22:286.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAydin F, Kulturoglu MO, Aslan F, Dogan L. Intraoperative frozen section analysis can be omitted in early breast cancer without significantly elevating reoperation rates. BMC Surg. 2025;25:347.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 2013;14:609\u0026ndash;18.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBoughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA. 2013;310:1455\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMontagna G, Laws A, Ferrucci M, Mrdutt MM, Sun SX, Bademler S, et al. Nodal burden and oncologic outcomes in patients with residual isolated tumor cells after neoadjuvant chemotherapy (ypN0i+): the OPBC-05/ICARO Study. J Clin Oncol. 2025;43:810\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMuslumanoglu M, Cabioglu N, Igci A, Karanlik H, Kocer HB, Senol K et al. Combined analysis of the MF18-02/MF18-03 NEO-SENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in breast cancer patients with good response to neoadjuvant chemotherapy when radiotherapy is provided. Cancer. 2024;1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evon Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796\u0026ndash;804.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHoussami N, Macaskill P, von Minckwitz G, Marinovich ML, Mamounas E. Meta-analysis of the association of breast cancer subtype and pathologic complete response to neoadjuvant chemotherapy. Eur J Cancer. 2012;48(18):3342\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKuerer HM, Sahin AA, Hunt KK, et al. Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999;230(1):72\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMougalian SS, Hernandez M, Lei X, et al. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol. 2016;2(4):508\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDominici LS, Negron Gonzalez VM, Buzdar AU, et al. Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer. 2010;116(12):2884\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTadros AB, Yang WT, Krishnamurthy S, Rauch GM, Smith BD, Valero V, et al. Identification of patients with documented pathologic complete response in the breast after neoadjuvant chemotherapy for omission of axillary surgery. JAMA Surg. 2017;152(7):665\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBarron AU, Hoskin TL, Day CN, Hwang ES, Kuerer HM, Boughey JC. Association of low nodal positivity rate among patients with ERBB2-positive or triple-negative breast cancer and breast pathologic complete response to neoadjuvant chemotherapy. JAMA Surg. 2018;153(12):1120\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCabioglu N, Ercan DO, Karatas I, Eroz E, Toprak S, Emiroğlu S, et al. Changing practice patterns in axillary management for patients with node-positive breast cancer towards increased use of sentinel lymph node biopsy alone after neoadjuvant chemotherapy: results of a survey (MF17-01) among Turkish surgeons. Langenbecks Arch Surg. 2025;410:196.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, Sentinel lymph node biopsy, Neoadjuvant chemotherapy, Frozen section, Paraffin section, HER2-positive, Triple-negative breast cancer, Axillary surgery, De-escalation","lastPublishedDoi":"10.21203/rs.3.rs-7900010/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7900010/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAxillary management in breast cancer has shifted significantly with the increasing use of neoadjuvant chemotherapy (NACT), particularly in biologically aggressive subtypes such as HER2-positive breast cancer and triple-negative breast cancer (TNBC). Intraoperative frozen section evaluation of sentinel lymph nodes (SLNs) has traditionally guided axillary dissection, but recent evidence suggests that omitting axillary dissection in patients with minimal or no residual disease provides comparable local control when combined with axillary radiotherapy. This study aimed to evaluate whether intraoperative frozen section or paraffin section assessment affects axillary management in patients who are clinically node negative (cN0) before NACT.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis retrospective study included 83 patients with HER2-positive breast cancer or TNBC treated between 2023 and 2025. All patients were clinically and radiologically node negative prior to NACT. SLN biopsy was performed using isosulfan blue, dual technique, indocyanine green, or combinations. Intraoperative frozen section analysis was performed in 59 patients, while paraffin section was used in 24 patients. Clinicopathological features, SLN positivity, pathological response rates, axillary recurrence, and surgical decisions were compared. Statistical analyses were performed using SPSS 18.0, with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 considered significant.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe mean age was 48.2 years. A pathological complete response (pCR) was achieved in 71% of patients, of whom 96.6% had negative SLNs. Among patients with partial response, 75% had negative SLNs. SLN positivity was observed in 8.5% (n\u0026thinsp;=\u0026thinsp;5) of patients in the frozen section group and 12.5% (n\u0026thinsp;=\u0026thinsp;3) in the paraffin section group. Axillary dissection was performed only in the frozen section group. No axillary recurrences occurred in either group after a median follow-up of 22 months. Paraffin section evaluation did not result in delayed treatment or increased recurrence.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn HER2-positive and TNBC patients with cN0 status before NACT and a good pathological response, frozen section analysis of SLNs does not influence surgical decision-making. Paraffin section evaluation represents a safe alternative, reducing operative time, anesthesia exposure, and healthcare costs. These findings support axillary de-escalation in selected high-response subgroups.\u003c/p\u003e","manuscriptTitle":"Sentinel Lymph Node Approach in HER2-Positive and Triple-Negative Breast Cancer with cN0 Status Prior to Neoadjuvant Chemotherapy: Frozen Section or Paraffin Section?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-25 11:13:35","doi":"10.21203/rs.3.rs-7900010/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"474a3afc-9ade-4803-87df-fffe1850586e","owner":[],"postedDate":"November 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-15T08:12:23+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-25 11:13:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7900010","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7900010","identity":"rs-7900010","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}