Sequencing of the lymphatic territories of the breast: Possibility of tertiary lymphatic territories after breast- conserving surgery: A preliminary study

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Moneer, Sherin Wagih Yassin, Ahmed Al Maksoud, Adel K Barsoum This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6771010/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 Lymphoscintigraphy (LSG) of the breast was mainly use for the diagnoses of the sentinel lymph node (SLN) of the breast. With breast LSG, the SLN was mainly observed at the ipsilateral axillary (IPLA) lymph nodes (LNs). However, many SLNs were observed at many extra-axillary lymphatic territories of the breast (LTB). This study included female patients with stage II breast cancer (BC). They underwent breast-conserving surgery. Studied Patients underwent modified techniques for breast LSG which were not aiming to diagnose the SLN. They were aiming to stage the LF of the breast in a sequential manner. After Covering the injection sites, the LF of the breast appeared at the ipsilateral internal mammary (IPLIM) LNs. When the observed IPLIM were further covered by lead shields, breast LF appeared at other three sites which were: mediastinal LNs, contralateral intra-mammary (CLIntM) LNs and pre-aortic LNs in the abdomen. Since the IPLA LNs are the primary LTB, the observed IPLIM LNs could be the secondary LTB. In addition, the mediastinal LNs, the CLIntM LNs and The pre-aortic LNs could be tertiary LTB. Accordingly, the present study suggested modifications for the staging of the TNM system of the breast and also the management of BC. Biological sciences/Cancer Health sciences/Anatomy Health sciences/Medical research Health sciences/Oncology Breast Conserving Surgery Breast Lymphoscintigraphy Tertiary Lymphatic Territories for the Breast Sequencing of Breast Lymph Flow Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Introduction The lymphatic drainage of the breast essentially involves the ipsilateral axilla [IPLA]. It constitutes the major primary lymphatic territory of the breast (1ryLTB). It drains approximately 75–85% of the lymph flow (LF) of the breast [ 1 ]. However, the remaining 15–25% of breast lymph drains into extra-axillary territories [ 1 – 4 ]. According to standard anatomy, the breast has two sets of lymphatics: the lymphatics of the skin of the overlying breast and the lymphatics of the parenchyma of the breast itself [ 5 ]. The breast skin drains away from the nipple radially to the IPLA lymph nodes [LNs], the ipsilateral internal mammary (IPLIM) LNs, and the ipsilateral supraclavicular LNs [ 6 ]. At the midline, these superficial lymphatics communicate to the other side [ 7 ]. The lymphatic drainage of the parenchyma of the breast starts from the lobules of the breast towards the retroarealar lymphatic plexus of the Sappey. This plexus is formed of larger ducts that communicate with the retro-mammary lymphatic plexus. Lymphatics from this wide lymphatic plexus penetrate the pectoralis major and serratus anterior muscles to reach the pectoral and central LNs of the IPLA and the IPLIM LNs. Some lymphatics pass through the axillary tail which penetrates the axillary floor through the foramen of Langer, and the lymphatics reach the subscapular (posterior) LNs of the IPLA [ 5 ]. Few small intramammary LNs are embedded in the parenchyma of the breast. These nodes intervene between the breast lymphatics and the regional LNs [ 5 , 7 ]. Additionally, few lymphatics penetrate the chest wall reaching the posterior intercostal LNs near the heads of the ribs which accompany the lateral branches of the posterior intercostal vessels [ 5 ]. Axillary LNs drain up to the apical LNs which drain into the blood via the ipsilateral subclavian lymph trunk (LT) [ 7 ]. The central axillary LNs are grouped around the intercostobrachial vessels. These LNs are drained by the lymphatics that accompany the vessels, which end at the upper posterior intercostal LNs. All posterior intercostal LNs drain into the blood via posterior mediastinal LT [ 7 ]. Additionally, at the midline the IM LNs and mediastinal LNs communicate from one side to another [ 5 ]. IM LNs are the anterior mediastinal LNs of the chest. They drain to the blood via the anterior mediastinal LT [ 7 ]. The mediastinal and subclavian lymph trunks (LTs) reach the blood at the junction of the subclavian and the internal jugular veins on the right side. On the left side, these trunks reach the blood via the thoracic duct [ 7 ]. According to the standard anatomy, breast cancer (BC) metastasize essentially to the IPLA LNs. However, BC metastases are infrequently reported to occur in almost all the previously reported anatomical sites. All these metastases were observed clinically and by PET/CT. In addition to IPLA LNs, BC metastases have been reported in IPLIM LNs [ 2 , 8 , 9 ], ipsilateral mediastinal LNs [ 10 – 14 ] and paravertebral LNs [ 15 ]. Additionally, BC metastases have been reported in contralateral axillary (CLA) LNs [ 9 , 12 , 16 – 23 ] and contralateral intramammary (CLIntM) LNs [ 24 ]. With the introduction of lymphoscintigraphy (LSG) in the 1970s, it was usually used for visualization of the sentinel lymph node (SLN) of the breast, which is the hypothetical first lymph node or group of nodes draining cancer cells. With LSG, the SLN was visualized mainly in the IPLA LNs [ 1 , 9 , 25 , 26 ]. However, the SLNs were also detected, although less frequently, at the previously reported extra-axillary anatomical lymphatic territories of the breast [ 5 , 7 ]. These territories were observed in various studies which ranged from 7–40% [ 1 , 4 ]. SLNs of the breast have been reported at the IPLIM LNs [ 1 , 9 , 25 ], the ipsilateral supraclavicular LNs [ 25 ], the contralateral IM (CLIM) LNs [ 28 ] and the CLA LNs [ 9 , 29 , 30 ]. For decades, breast LSG has been used only for SLN localization. However, the LF of the breast was not staged or sequenced among the previously reported extra-axillary territories of the breast and these findings did not add any implications for the management of BC. In the present study, the LF of the breast tissue was studied via LSG after BCS and TAD. In this study the LF was not used to localize the SLN of the breast. It was trying to stage the LF of the breast in a sequenced manner from one group of LNs to another group. For allowing this staging, a modified technique for LSG was used. Patients and methods The study included eleven stage ll BC female patients. Their tumors were less than 3 cm (T1-2 N1 M0). All patients were previously treated with breast-conserving surgery (BCS) with TAD. All patients received adjuvant therapy, when indicated. However, the axillary and IM regions were not irradiated in all cases. All selected patients were free of local or systemic metastasis (based on PET/CT). All studied patients gave their informed consent to share in this study and for publication. The used Techniques in this study were in accordance with the protocol that was designated "SCBU-MEH-GOTHI-15-3-06" . In this protocol, patients were enrolled for breast LSG on the operated side. All patients received four periarealar superficial subcutaneous injections of Tc99m nanocolloid at 3, 6, 9 and 12 O’clock, in a small volume (<0.5 ml each), with a total activity range of 37-74 Mbq. Imaging was performed in the supine position on a Siemens e-cam single head gamma camera with an all-parallel-hole collimator. Planar images were acquired basically in anterior projection and oblique projection, on demand. At the beginning of the present study, images were acquired via the standard technique which adjusts the gamma camera according to a fixed time (30-60 minutes' post injection). However, with the observed preliminary findings, there was no flow of the injected radioactive material away from the visualized 4 injection sites (Fig 1). Accordingly, we added two modifications to the original standard LSG technique: The 4 injection sites were covered with complete lead shielding. The gamma-camera machine was adjusted to image at preset counts of >300,000 counts per projection instead of acquisition at a preset time. Owing to these two modifications, LF started to appear. When the end point of scanning was reached (> 300,000 counts per projection), the final picture of the scan was imaged with removal of all lead shields to show all areas of lymphatic uptake in one film. When any lymphatic territory was visualized, it was further covered by lead shields, and the patient was again further scanned until a second end point was further reached (>300,000 counts per projection). Radioactive marks were used for anatomical localization of the visualized hot spots, when needed Results Clinical examination of all the operated breasts revealed variable mild to moderate degrees of breast skin oedema. Additionally, in the preliminary study, LSG showed no LF to the ipsilateral dissected axilla in all cases, and there was prolonged retention of the injected radioactive material at the injection sites (Fig 1). With the modified technique of LSG in the present study, LF appeared at the ipsilateral IM LNs in 9 studied patients. In these cases, the end point was reached after 2-4 hours (Fig 2 and Table 1). In these 9 patients, the visualized IM LNs were further covered by lead shields, and these patients continued further scanning until the end point was reached again (>300,000 counts per projection). This second end point required further scanning for more 2-4 hours. These nine cases showed further LF to other new sites, which were observed in 3 territories: 1- Flow to the ipsilateral mediastinum, which was visualized in an oblique view midway between the tip of the shoulder and the sternum. This LF was observed in 6 patients (Fig 3 and Table 2). 2- Flow to the contralateral side superficial to the ribs in 2 patients. These observed sites could be CLIntM LNs (Fig 4 and Table 2). 3- Flow to the preaortic LNs in the abdomen which occurred in one patient (Fig 5 and Table 2). Among the eleven cases, in which the injection sites were covered by lead shields, 2 cases showed no LF to the IM LNs. These 2 cases were scanned at various intervals for up to 24 hours; however, these 2 cases did not show any LF away from the injection sites (Fig 6 and Tables 1 and 3). Figure 7 shows the scheme of the study and its results (Visual Abstract). Discussion In the present study, the observed degree of lymphedema of the residual breast tissue indicated a compromised degree of LF of the breast. Additionally, the used standard technique of breast LSG in the present study revealed no LF away from the injection sites for up to 60 minutes. These two observations could be attributed to the previous TAD and to the previously performed bosting dose of radiotherapy (RT) to the residual breast in the studied patients. The LF of the breast after BCS and TAD was studied by other authorities. They only showed LF of the breast to the CLA LNs [9, 29, 30]. Also, these studies used the standard technique of LSG which only localized the SLN. In contrast to the present study, we used modified techniques for LSG. These modifications were the covering of the injection sites and also adjustment of the gamma camera machine to image according to a fixed count instead of a fixed time. These two modifications allowed flow of the injected radioactive material away from the injection sites. In the present study, all studied cases showed no flow to the IPLA LNs. However, in the present study, many studied patients, showed LF to many extra-axillary lymphatic territories for the breast. In the present study, the first observed extra-axillary territory for the breast was the IPLIM LNs (Fig 2 and Table 1). The LF to this territory reached the majority of the studied cases (9/11 - 81.8%) and appeared after more than 2 hours of scanning. Similarly, other studies have shown BC metastases at the IPLIM LNs [2, 8, 9]. Also, other authorities showed the SLN of the breast at the IPLIM [1, 9, 25, 26]. However, the observed LF to these IPLIM LNs with LSG in the present study, were not a mere simple diagnosis of the SLN. It showed that the IPLIM LNs were the only first observed lymphatic territory for the breast. Additionally, the LF of the breast to this first territory required more than 2-4 hours. Since the IPLA LNs are known to be the 1ryLTB, this second post-1ryLTB could be the secondary lymphatic territory of the breast (2ndLTB). When the visualized IPLIM LNs (2ndLTB) by LSG in the nine studied cases were covered by lead shields, they showed further LF to three new sites. These 3 new sites were: mediastinal LNs (6 patients), CLIntM LNs (2 patients), and one case revealed LF to the preaortic LNs in the abdomen. In the present study, all these new lymphatic territories of the breast were observed in sequence to the previously covered 2ndLTB. Accordingly, these sites could be suggested to be tertiary lymphatic territories for the breast (3ryLTB). In the present study, the observed LF from the breast to the ipsilateral mediastinum (Fig 3 and Table 2) was the most commonly observed 3ryLTB (6/9). This observed LF from the breast to the mediastinum could be attributed either to retrograde spread from the IM LNs or possibly via direct lymph vessels, which accompany the lateral branches of the posterior intercostal vessels that drain to the posterior intercostal LNs, which are present at the heads of the ribs [5]. However, regardless of the route of this LF to the mediastinum, the present study and many other authorities have documented mediastinal BC metastases [10-14]. The observed LF to the CLIntM LNs in the present study (Fig 4 and Table 2) could be mediated via the superficial crossing lymphatics at the midline [7]. However, this observed LF from the breast to the CLIntM LNs was also reported by many authorities, who described BC metastasis at the CLIntM LNs of the breast [24]. Since CLIntM LNs usually drain to the CLA LNs of the breast {5, 7]. Thus, the observed LF to the CLIntM LNs in the present study could be an in-transient pathway to the CLA LNs, which have been reported to be one of the extra-axillary BC metastases [ 9, 12, 16-23]. Accordingly, we believe that further studies are needed to follow further scanning of cases with LF to CLIntM LNs to verify whether they represent an initial draining lymphatic station passing to CLA LNs or not. In the present study, the observed LF from the breast to the preaortic LNs in the abdomen was an unexpected finding. Although this finding was observed only in one patient (1/9), (Fig 5 and Table 2), it still requires an explanation. Revising the standard anatomy revealed that the LF of the lower outer part of the breast could drain along the lymphatics, which accompany the lateral branches of the posterior intercostal vessels that drain to the posterior mediastinal LNs [5]. These lower nodes are reported to drain via the descending intercostal LT, which passes downwards through the aortic orifice of the diaphragm and drains to the cisternachyli [7]. Via this route, LF could reach the preaortic LNs via retrograde flow from the cisternachyli. These lower posterior mediastinal (paravertebral) LN metastases from BC have been previously reported [15]. Whatever the route of this observed LF of the breast to the preaortic LNs, it is only worth documentation in the present study, and further studies are needed to confirm this finding and its possible route. In the present study, "no LF pattern" was observed in 2 studied cases (Fig 6 and Table 1 and 3) . It showed no flow of the radioactive material away from the injection sites for up to 24 hours. This "no LF pattern" was a questionable observation. It was observed by many authorities but without explanation [1, 25]. In the present study, the clinical history of these 2 cases was revised. These 2 cases were having medial tumors and were treated by wide local excision. This procedure could have interrupted the medial lymphatics, which prevented the LF of the breast from travelling to the IM LNs. Regardless of the explanation of this "no LF pattern" it worth an important observation. It showed that the cases which showed LF to the 2ndLTB were the cases which showed LF to the 3ryLTB and the cases which did not show LF to the 2ryLTB were the cases which showed no flow to the 3ryLTB. According to this observation, it could reveal that the 2ndLTB could be a preliminary step that could allow LF to the other 3ryLTB. Whatever these conclusions in this study, the observed "no LF pattern" in these 2 studied cases, requires further analysis, especially by prolonging the scanning time for more than 24 hours. Apparently, the present study shows similar findings to those of other many previous studies over decades [1, 9 , 29-30]. These previous studies and also the present study similarly showed many of the extra-axillary lymphatic territories of the breast via LSG. However, the present study differs from the previous studies in many aspects: Previous studies were diagnosing the SLN, while the present study was not localizing the SLNs. With the used modified technique of LSG in the present study, it allowed staging of the lymphatic territories of the breast in a sequential manner. Accordingly, the observed findings in the present study and also the similar observed findings in many previous studies, worth consideration in the following implications on the diagnoses and management of breast cancer: The IPLA LNs are the well-known 1ryLTB. Also, the IPLIM LNs are well known of the extra-axillary lymphatic territories of the breast. However, the findings of the present study showed that the IPLIM LNs could be the most important 2ndLTB. Also, the other observed extra-axillary LTB in the present study, could be considered to be the 3ryLTB. The important factors that push the LF of the breast to reach extra-axillary territories were not suggested so far. However, the blocking of the IPLA LNs could be suggested to be an important factor for directing the LF of the breast to extra-axillary LTB. This blocking was achieved either by TAD, as observed in the present study, or by their major obstruction by metastases, as observed in many studies [16, 17]. According to the present study, BC recurrence after BCS and TAD should require more investigations in order to evaluate the nodal status after TAD. It should include assessment of the secondary and tertiary lymphatic territories of the breast, which may require U/S, CT, PET/CT and SLN biopsy. For many decades, extra-axillary BC metastases have been described by PET/CT or even by clinical or pathological examination [2, 3, 10-23]; however, these extra-axillary lymphatic metastases from BC have not been verified to be blood-born or lymph-born metastases. However, according to the present study and also according to other studies, which used LSG [1, 4, 9, 25-30], confirm that these reported extra-axillary metastases from BC should be lymph-born metastases, and these extra-axillary BC metastases should not be considered systemic metastases. Actually, these metastases could be considered to be a "special category of regional lymphatic BC metastases". This term was also described by other authorities [23]. Accordingly, the staging system of BC should be modified to include this " special category of regional lymphatic BC metastases" in the accepted staging system of BC, which is now the Tumor, Nodes, Metastases (TNM) [31]. Since the present TNM staging system of the breast reveals that BC metastases at the IPLIM LNs, with involved IPLA LNs, are now designated "N3" and "Stage IIIc" [31], we can suggest that solitary BC metastases at the 3ryLTB should be designated "N4" and "Stage llld" instead of being designated "M+Ve" and "Stage IV" . According to the previously suggested modifications to the TNM staging system of BC, we can suggest that the management of BC patients with solitary extra-axillary metastases should receive a local therapy (RT or surgery) in addition to the standard systemic chemotherapy. This postulation was also described by other authorities [23]. However, prospective controlled trials are needed to validate our suggested postulations in the present study. Conclusion The LF of the breast is primarily to the IPLA LNs, which are well known to be the 1ryLTB. In the present study, BC patients with BCS and TAD were studied by modified breast LSG. These modifications forced the LF of the breast to many extra-axillary territories of the breast and also allowed staging of the LF of the breast in a sequenced manner. This study revealed that the IPLIM LNs could be the 2ndLTB. Also 3ryLTB were suggested. These observed 3ryLTB were the ipsilateral mediastinal LNs, the CLIntM LNs, and the preaortic LNs in the abdomen. According to the present study, the 2ndLTB was observed to be the essential pathway that could allow LF of the breast to the 3ryLTB. Accordingly, tumor recurrence in patients with BCS and TAD should require further assessment of their nodal status at the secondary and tertiary lymphatic territories. The findings of the present study, and according to other studies, suggest that extra-axillary BC metastases are lymph-born rather than blood-born metastases. Additionally, these lymph-born metastases should be considered to be a "special category of regional lymphatic BC metastases". Accordingly, BC metastases at 3ryLTB should be designated "N4" and "Stage lllD" instead of being designated "M + Ve" and "Stage IV" . Additionally, the management of BC patients with solitary extra-axillary metastases should be managed by local therapy (RT or surgery), in addition to standard systemic chemotherapy. With the observed findings in the present study, further studies are required to confirm the presence of 3ryLTB. Abbreviations Breast cancer: BC Contralateral Axillary: CLA Contralateral internal mammary: CLIM Contralateral intra-mammary: CLIntM Internal mammary: IM Ipsilateral axilla: IPLA Ipsilateral internal mammary: IPLIM Lymph node: LN Lymph nodes: LNs Lymphatic territory of the breast: LTB Lymph trunk: LT Lymph trunks: LTs Lymphoscintigraphy: LSG Primary lymphatic territory of the breast: 1ryLTB Radiotherapy RT Sentinel lymph node: SLN Sentinel lymph nodes: SLN s Secondary lymphatic territory of the breast: 2ndLTB Tertiary lymphatic territory of the breast: 3ryLTB Declarations Acknowledgement The authors thank the studied patients who provided their consent which revealed the observed results. Statements and Declarations Approval statements: The procedures performed in the studied humans were accepted by the Scientific Committee of the Breast Unit of Al-Matareya Educational Hospital which was designated "SCBU-MEH-GOTHI-15-3-06" . The ethical standards of this protocol were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.Data availability: The datasets generated during the current study are available only from the corresponding author upon reasonable request. Authors’ contributions and consent for publication: MM is the primary author. He was involved in all stages of the paper’s preparation. YS was responsible for all the work on the gamma camera. MA and BA made significant contributions to the article’s design. In combination, all the authors provided supervisory oversight, reviewed the article and gave final approval for publication. Funding: declare: The authors did not receive funding, grants, or other support from any organization for this submitted work. 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Ther . 24(2), 90–93 (2015). https//doi. 10.4274/mirt.91300. Amin, M.B. et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J. Clin . 67(2), 93-99 (2017). https//doi.10.3322/caac.21388 . Tables Table 1: Results of 11 cases with LSG images at different time intervals (1-8 hours). Imaging Time 1 Hr 2-4 Hr 6-8 Hr Anatomical Sites +Ve -Ve +Ve -Ve +Ve -Ve Periareolar Injection Sites 11 0 11 0 11 0 Ipsilateral Axillary LNs 0 11 0 11 0 11 Contralateral Internal Mammary LNs 0 11 9 2 9 2 LNs: Lymph nodes Hr: Hour +Ve: Positive -Ve: Negative Table 2: Results of 9 cases with LSG images at different time intervals (1-8 hours). Imaging Time 1 Hr 2-4 Hr 6-8 Hr Anatomical Sites +Ve -Ve +Ve -Ve +Ve -Ve Periareolar Injection Sites 9 0 9 0 9 0 Ipsilateral Axillary LNs 0 9 0 9 0 9 Contralateral Internal-mammary LNs 0 9 9 0 9 0 Ipsilateral Mediastinal LNs 0 9 9 0 6 3 Ipsilateral Intra-Mammary LNs 0 9 9 0 2 7 Preaortic LNs 0 9 9 0 1 8 LNs: Lymph nodes Hr: Hour +Ve: Positive -Ve: Negative Table 3: Results of 2 cases with LSG images at different time intervals (1-24 hours). Imaging Time 1 Hr 2-4 Hr 6-8 Hr 24 Hr Anatomical Sites +Ve -Ve +Ve -Ve +Ve -Ve +Ve -Ve Periareolar Injection Sites 2 0 2 0 2 0 2 0 Ipsilateral Axillary LNs 0 2 0 2 0 2 0 2 Contralateral Internal Mammary LNs 0 2 0 2 0 2 0 2 Ipsilateral Mediastinal LNs 0 2 0 2 0 2 0 2 Ipsilateral Intramammary LNs 0 2 0 2 0 2 0 2 Preaortic LNs 0 2 0 2 0 2 0 2 LNs: Lymph nodes Hr: Hour +Ve: Positive -Ve: Negative Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6771010","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":478897392,"identity":"dbea3a3f-44ad-4ed4-bd5a-453c4dc79955","order_by":0,"name":"Mohamed M. Moneer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYDAD+/kPGx8wMBwgQYsBQ3KzAala0tskiNKiO+104uOCCpt8c4aDbdU8NXfk+BmYHz66gUeL2e3czcYzzqRZ7mxsbLvNc+yZsWQDm7FxDn4t26R52w4bMBxmBGphO5y44QAPmzRhLf/+GzAcY2wr5vlHtJaGAwYGZxjbmIHWEaVlszHPsWQDyRmMzZJz+w4bSzYT9svGxzw1dgb8EuwPP7z5dliOn7354WN8WlAAEw+IZCZWOQgw/iBF9SgYBaNgFIwYAACglk9cEyMVSQAAAABJRU5ErkJggg==","orcid":"","institution":"Al Matareya Educational Hospital, GOTHI, Ministry of Health and Population","correspondingAuthor":true,"prefix":"","firstName":"Mohamed","middleName":"M.","lastName":"Moneer","suffix":""},{"id":478897393,"identity":"d3158f3a-ca3c-4e30-b753-94b5c6488e71","order_by":1,"name":"Sherin Wagih Yassin","email":"","orcid":"","institution":"Cairo University KasrAlainy","correspondingAuthor":false,"prefix":"","firstName":"Sherin","middleName":"Wagih","lastName":"Yassin","suffix":""},{"id":478897394,"identity":"a557a17b-90c6-455d-9fd2-464a13f599de","order_by":2,"name":"Ahmed Al Maksoud","email":"","orcid":"","institution":"Frimley Health NHS Foundation Trust","correspondingAuthor":false,"prefix":"","firstName":"Ahmed","middleName":"Al","lastName":"Maksoud","suffix":""},{"id":478897395,"identity":"904ac0d1-89c9-4aa9-befd-571f6fe749a4","order_by":3,"name":"Adel K Barsoum","email":"","orcid":"","institution":"Al Matareya Educational Hospital, GOTHI, Ministry of Health and Population","correspondingAuthor":false,"prefix":"","firstName":"Adel","middleName":"K","lastName":"Barsoum","suffix":""}],"badges":[],"createdAt":"2025-05-28 20:53:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6771010/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6771010/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85993490,"identity":"7e34363d-00c0-44a2-92c3-0ca0c7b78625","added_by":"auto","created_at":"2025-07-04 05:40:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":310148,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScanning after 60 minutes – There was no flow away from the injection sites with radioactive marks at the shoulder and SSN, and there was no flow to the axilla.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eInj: 4 periareolar injection site\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003es\u003c/strong\u003e\u003cem\u003e\u003cstrong\u003e; SSN: Suprasternal Notch; Axilla: no lymph flow\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e to the axilla\u003c/strong\u003e\u003cem\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/75a6bace2795cc9827761505.png"},{"id":85993496,"identity":"a7fb7126-33b9-46ac-ad5c-6a7f4c4deaf7","added_by":"auto","created_at":"2025-07-04 05:40:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":435397,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLymph flow to ipsilateral internal mammary lymph nodes (black arrow) with radioactive marks at the shoulder and SSN and with no lymph flow to the axilla.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eInj: 4 periareolar injection site\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003es;\u003c/strong\u003e\u003cem\u003e\u003cstrong\u003e SSN: Suprasternal Notch; Axilla: no lymph flow\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e to the axilla.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/ea8f5a6cebed15631c7c5389.png"},{"id":85993506,"identity":"38511ffd-16bf-4993-a4f5-8582820bf113","added_by":"auto","created_at":"2025-07-04 05:40:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":559314,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLymph flow to mediastinal lymph nodes (black arrow) in oblique view with radioactive marks at the shoulder and SSN.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eSSN: Suprasternal Notch; IM: Internal Mammary Lymph Nodes; Inj: 4 periareolar injection sites.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/a3f1714fa0ed6d7ff8525942.png"},{"id":85993494,"identity":"05f976d3-f4d5-4c76-9e86-94dcb27dc520","added_by":"auto","created_at":"2025-07-04 05:40:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":1092266,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLymph flow to the contralateral intramammary lymph nodes (black arrow).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eInj: periareolar injection sites; IM: Internal Mammary Lymph Nodes Kid: Kidneys.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/26239fea4a7de0c3255fb506.png"},{"id":85993503,"identity":"60c4dbf0-eece-4cee-8dbb-141177bce4c9","added_by":"auto","created_at":"2025-07-04 05:40:08","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":476894,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eLymph flow to preaortic lymph nodes in the abdomen (black double arrow)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInj: periareolar\u003c/strong\u003e\u003cem\u003e\u003cstrong\u003einjection sites; IM: internal mammary; Kid: kidneys\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/e7bddf4957f686e3e958e305.png"},{"id":85993521,"identity":"6051e9f6-2118-4e9f-ae5c-d3548e7510e7","added_by":"auto","created_at":"2025-07-04 05:40:10","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":913563,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eNo lymph flow away from the injection sites for up to 24 hours.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eInj: periareolar injection sites; Kid: kidneys\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig6.png","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/e3a80b56d7b35f3e967b8454.png"},{"id":85993504,"identity":"6d208ecc-d5b6-47a2-ad50-7195e5fe771e","added_by":"auto","created_at":"2025-07-04 05:40:08","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":2451446,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme of the study and summary of the results (Visual Abstract).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eLNs: lymph nodes; RT: radiotherapy; Ch Th: chemotherapy; BCS: breast-conserving surgery; TAD: total axillary dissection.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Fig7VisualAbstract.png","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/90de49439e4e8b1e9fde00bf.png"},{"id":107346184,"identity":"18f91470-b5f2-49e8-bee3-d1d24c0a5843","added_by":"auto","created_at":"2026-04-20 15:11:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":12493536,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/e50af8b0-5cdc-4458-83d7-b78937fe8545.pdf"},{"id":85993501,"identity":"2f41389c-e485-4e94-abba-63a31545ceb0","added_by":"auto","created_at":"2025-07-04 05:40:08","extension":"mp4","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":9706500,"visible":true,"origin":"","legend":"","description":"","filename":"VisualAbstractVideo.mp4","url":"https://assets-eu.researchsquare.com/files/rs-6771010/v1/bddd74bea847edeae8b2197c.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sequencing of the lymphatic territories of the breast: Possibility of tertiary lymphatic territories after breast- conserving surgery: A preliminary study","fulltext":[{"header":"Introduction","content":"\u003cp\u003e \u003cb\u003eThe lymphatic drainage of the breast essentially involves the ipsilateral axilla [IPLA]. It constitutes the major primary lymphatic territory of the breast (1ryLTB). It drains approximately 75\u0026ndash;85% of the lymph flow (LF) of the breast\u003c/b\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. \u003cb\u003eHowever, the remaining 15\u0026ndash;25% of breast lymph drains into extra-axillary territories\u003c/b\u003e [\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eAccording to standard anatomy, the breast has two sets of lymphatics: the lymphatics of the skin of the overlying breast and the lymphatics of the parenchyma of the breast itself\u003c/b\u003e [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. \u003cb\u003eThe breast skin drains away from the nipple radially to the IPLA lymph nodes [LNs], the ipsilateral internal mammary (IPLIM) LNs, and the ipsilateral supraclavicular LNs\u003c/b\u003e [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. \u003cb\u003eAt the midline, these superficial lymphatics communicate to the other side\u003c/b\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. \u003cb\u003eThe lymphatic drainage of the parenchyma of the breast starts from the lobules of the breast towards the retroarealar lymphatic plexus of the Sappey. This plexus is formed of larger ducts that communicate with the retro-mammary lymphatic plexus. Lymphatics from this wide lymphatic plexus penetrate the pectoralis major and serratus anterior muscles to reach the pectoral and central LNs of the IPLA and the IPLIM LNs. Some lymphatics pass through the axillary tail which penetrates the axillary floor through the foramen of Langer, and the lymphatics reach the subscapular (posterior) LNs of the IPLA\u003c/b\u003e [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. \u003cb\u003eFew small intramammary LNs are embedded in the parenchyma of the breast. These nodes intervene between the breast lymphatics and the regional LNs\u003c/b\u003e [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. \u003cb\u003eAdditionally, few lymphatics penetrate the chest wall reaching the posterior intercostal LNs near the heads of the ribs which accompany the lateral branches of the posterior intercostal vessels\u003c/b\u003e [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eAxillary LNs drain up to the apical LNs which drain into the blood via the ipsilateral subclavian lymph trunk (LT)\u003c/b\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eThe central axillary LNs are grouped around the intercostobrachial vessels. These LNs are drained by the lymphatics that accompany the vessels, which end at the upper posterior intercostal LNs. All posterior intercostal LNs drain into the blood via posterior mediastinal LT\u003c/b\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. \u003cb\u003eAdditionally, at the midline the IM LNs and mediastinal LNs communicate from one side to another\u003c/b\u003e [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eIM LNs are the anterior mediastinal LNs of the chest. They drain to the blood via the anterior mediastinal LT\u003c/b\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eThe mediastinal and subclavian lymph trunks (LTs) reach the blood at the junction of the subclavian and the internal jugular veins on the right side. On the left side, these trunks reach the blood via the thoracic duct\u003c/b\u003e [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eAccording to the standard anatomy, breast cancer (BC) metastasize essentially to the IPLA LNs. However, BC metastases are infrequently reported to occur in almost all the previously reported anatomical sites. All these metastases were observed clinically and by PET/CT. In addition to IPLA LNs, BC metastases have been reported in IPLIM LNs\u003c/b\u003e [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], \u003cb\u003eipsilateral mediastinal LNs\u003c/b\u003e [\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] \u003cb\u003eand paravertebral LNs\u003c/b\u003e [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. \u003cb\u003eAdditionally, BC metastases have been reported in contralateral axillary (CLA) LNs\u003c/b\u003e [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR17 CR18 CR19 CR20 CR21 CR22\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] \u003cb\u003eand contralateral intramammary (CLIntM) LNs\u003c/b\u003e [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eWith the introduction of lymphoscintigraphy (LSG) in the 1970s, it was usually used for visualization of the sentinel lymph node (SLN) of the breast, which is the hypothetical first lymph node or group of nodes draining cancer cells. With LSG, the SLN was visualized mainly in the IPLA LNs\u003c/b\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. \u003cb\u003eHowever, the SLNs were also detected, although less frequently, at the previously reported extra-axillary anatomical lymphatic territories of the breast\u003c/b\u003e [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. \u003cb\u003eThese territories were observed in various studies which ranged from 7\u0026ndash;40%\u003c/b\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. \u003cb\u003eSLNs of the breast have been reported at the IPLIM LNs\u003c/b\u003e [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], \u003cb\u003ethe ipsilateral supraclavicular LNs\u003c/b\u003e [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], \u003cb\u003ethe contralateral IM (CLIM) LNs\u003c/b\u003e [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] \u003cb\u003eand the CLA LNs\u003c/b\u003e [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003eFor decades, breast LSG has been used only for SLN localization. However, the LF of the breast was not staged or sequenced among the previously reported extra-axillary territories of the breast and these findings did not add any implications for the management of BC.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eIn the present study, the LF of the breast tissue was studied via LSG after BCS and TAD. In this study the LF was not used to localize the SLN of the breast. It was trying to stage the LF of the breast in a sequenced manner from one group of LNs to another group. For allowing this staging, a modified technique for LSG was used.\u003c/b\u003e \u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003e\u003cstrong\u003eThe study included\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;eleven stage ll BC female patients. Their tumors were less than 3 cm (T1-2 N1 M0). All patients were previously treated with\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ebreast-conserving surgery (BCS) with TAD. All patients received adjuvant therapy, when indicated. However, the axillary\u0026nbsp;and IM regions were not irradiated in all cases. All selected patients were free of local or systemic metastasis (based on PET/CT). All studied patients gave their informed consent to share in this study and for publication.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe used Techniques\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;in this study were in accordance with the protocol that was designated \u003cem\u003e\u0026quot;SCBU-MEH-GOTHI-15-3-06\u0026quot;\u003c/em\u003e. In this protocol, patients were enrolled for breast LSG on the operated side. All patients received four periarealar superficial subcutaneous injections of Tc99m nanocolloid\u0026nbsp;at 3, 6, 9 and 12 O\u0026rsquo;clock, in a small volume (\u0026lt;0.5 ml each), with a total activity range\u0026nbsp;of 37-74 Mbq. Imaging was performed in the supine position on a Siemens e-cam single head gamma camera with an all-parallel-hole collimator. Planar images were acquired basically in anterior projection\u0026nbsp;and oblique projection, on demand. At the beginning of the present study, images were acquired via the standard technique which adjusts the gamma camera according to a fixed time (30-60 minutes\u0026apos; post injection). However, with the observed preliminary findings, there was no flow of the injected radioactive material away from the visualized 4 injection sites (Fig 1). Accordingly, we added two modifications to the original standard LSG technique:\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eThe 4 injection sites were covered with complete lead shielding.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eThe gamma-camera machine was adjusted to image\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eat preset counts of \u0026gt;300,000 counts per projection instead of\u0026nbsp;acquisition\u0026nbsp;at a preset time.\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eOwing to these two modifications, LF started to appear. When the end point of scanning was reached (\u0026gt;\u003c/strong\u003e\u003cstrong\u003e300,000\u0026nbsp;counts per\u0026nbsp;projection),\u0026nbsp;the final picture of the scan was imaged with removal of all lead shields to show all areas of lymphatic uptake in one film.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhen any lymphatic territory was visualized, it was further covered by lead shields, and the patient was again further scanned until a second end point was further reached (\u0026gt;300,000 counts per projection). Radioactive marks were used for anatomical localization of the visualized hot spots, when needed\u003c/strong\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eClinical examination of all the operated breasts revealed variable mild to moderate degrees of breast skin oedema.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAdditionally, in the preliminary study,\u0026nbsp;LSG showed no\u0026nbsp;LF\u0026nbsp;to the ipsilateral dissected\u0026nbsp;axilla\u0026nbsp;in all cases, and there was prolonged retention of the injected radioactive material at the injection sites (Fig 1). With the modified technique of LSG in the present study, LF\u0026nbsp;appeared at the\u0026nbsp;ipsilateral IM\u0026nbsp;LNs in\u0026nbsp;9 studied patients. In these cases,\u0026nbsp;the end point was reached\u0026nbsp;after 2-4 hours (Fig 2 and Table 1). In these 9 patients, the visualized IM LNs were further covered by lead shields, and these patients continued further scanning until the end point was reached again (\u0026gt;300,000 counts per projection). This\u0026nbsp;second end point required further scanning for more 2-4 hours.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThese nine cases showed further\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eLF\u0026nbsp;to other new sites, which were observed in 3 territories:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1- Flow to the ipsilateral mediastinum, which was visualized in an oblique view midway between the tip of the shoulder and the sternum. This LF was observed in 6 patients (Fig 3 and Table 2).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2- Flow to the contralateral side superficial to the ribs in 2 patients. These observed sites could be CLIntM LNs (Fig 4 and Table 2).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e3- Flow to the preaortic LNs in the abdomen\u0026nbsp;which occurred\u0026nbsp;in one patient (Fig 5 and Table 2).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAmong the eleven cases, in which the injection sites were covered by lead shields, 2 cases showed no LF to the IM LNs. These 2 cases were scanned at various intervals for up to 24 hours; however, these 2 cases did not show any LF away from the injection sites (Fig 6 and Tables 1 and 3).\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFigure 7 shows the scheme of the study and its results (Visual Abstract).\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cstrong\u003eIn the present study, the observed degree of lymphedema of the residual breast tissue indicated a compromised degree of LF of the breast. Additionally, the used standard technique of breast LSG in the present study revealed no LF away from the injection sites for up to 60 minutes. These two observations could be attributed to the previous TAD and to the previously performed bosting dose of radiotherapy (RT) to the residual breast in the studied patients.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe LF of the breast after BCS and TAD was studied by other authorities. They only showed LF of the breast to the CLA LNs [9, 29, 30]. Also, these studies used the standard technique of LSG which only localized the SLN. In contrast to the present study, we used modified techniques for LSG. These modifications were the covering of the injection sites and also adjustment of the gamma camera machine to image according to a fixed count instead of a fixed time. These two modifications allowed flow of the injected radioactive material away from the injection sites. In the present study, all studied cases showed no flow to the IPLA LNs. However, in the present study, many studied patients, showed LF to many extra-axillary lymphatic territories for the breast.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIn the present study, the first observed extra-axillary territory for the breast was the IPLIM LNs (Fig 2 and Table 1). The LF to this territory reached the majority of the studied cases (9/11 - 81.8%) and appeared after more than 2 hours of scanning. Similarly, other studies have shown BC metastases at the IPLIM LNs [2, 8, 9]. Also, other authorities showed the SLN of the breast at the IPLIM [1, 9, 25, 26]. However, the observed LF to these IPLIM LNs with LSG in the present study, were not a mere simple diagnosis of the SLN. It showed that the IPLIM LNs were the only first observed lymphatic territory for the breast. Additionally, the LF of the breast to this first territory required more than 2-4 hours. Since the IPLA LNs are known to be the 1ryLTB, this second post-1ryLTB could be the secondary lymphatic territory of the breast (2ndLTB).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhen the visualized IPLIM LNs (2ndLTB) by LSG in the nine studied cases were covered by lead shields, they showed further LF to three new sites. These 3 new sites were: mediastinal LNs (6 patients), CLIntM LNs (2 patients), and one case revealed LF to the preaortic LNs in the abdomen. In the present study, all these new lymphatic territories of the breast were observed in sequence to the previously covered 2ndLTB. Accordingly, these sites could be suggested to be tertiary lymphatic territories for the breast (3ryLTB).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIn the present study, the observed LF from the breast to the ipsilateral mediastinum (Fig 3 and Table 2) was the most commonly observed 3ryLTB (6/9). This observed LF from the breast to the mediastinum could be attributed either to retrograde spread from the IM LNs or possibly via direct lymph vessels, which accompany the lateral branches of the posterior intercostal vessels that drain to the posterior intercostal LNs, which are present at the heads of the ribs [5]. However, regardless of the route of this LF to the mediastinum, the present study and many other authorities have documented mediastinal BC metastases [10-14].\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe observed LF to the CLIntM LNs in the present study (Fig 4 and Table 2) could be mediated via the superficial crossing lymphatics at the midline [7]. However, this observed LF from the breast to the CLIntM LNs was also reported by many authorities, who described BC metastasis at the CLIntM LNs of the breast [24]. Since CLIntM LNs usually drain to the CLA LNs of the breast {5, 7]. Thus, the observed LF to the CLIntM LNs in the present study could be an in-transient pathway to the CLA LNs, which have been reported to be one of the extra-axillary BC metastases [\u003c/strong\u003e\u003ca href=\"https://www.clinical-breast-cancer.com/article/S1526-8209(11)70740-6/abstract\" title=\"Correspondence information about the author Rachel Wellner\"\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/a\u003e\u003cstrong\u003e9, 12, 16-23]. Accordingly, we believe that further studies are needed to follow further scanning of cases with LF to CLIntM LNs to verify whether they represent an initial draining lymphatic station passing to CLA LNs or not.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIn the present study, the observed LF from the breast to the preaortic LNs in the abdomen was an unexpected finding. Although this finding was observed only in one patient (1/9), (Fig 5 and Table 2), it still requires an explanation. Revising the standard anatomy revealed that the LF of the lower outer part of the breast could drain along the lymphatics, which accompany the lateral branches of the posterior intercostal vessels that drain to the posterior mediastinal LNs [5]. These lower nodes are reported to drain via the descending intercostal LT, which passes downwards through the aortic orifice of the diaphragm and drains to the cisternachyli [7]. Via this route, LF could reach the preaortic LNs via retrograde flow from the cisternachyli. These lower posterior mediastinal (paravertebral) LN metastases from BC have been previously reported [15]. Whatever the route of this observed LF of the breast to the preaortic LNs, it is only worth documentation in the present study, and further studies are needed to confirm this finding and its possible route.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIn the present study, \u003cem\u003e\u0026quot;no LF pattern\u0026quot;\u003c/em\u003e was observed in 2 studied cases\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e(Fig 6 and Table 1 and 3)\u003c/strong\u003e\u003cstrong\u003e. It showed no flow of the radioactive material away from the injection sites for up to 24 hours. This \u003cem\u003e\u0026quot;no LF pattern\u0026quot;\u003c/em\u003e was a questionable observation. It was observed by many authorities but without explanation [1, 25]. In the present study, the clinical history of these 2 cases was revised. These 2 cases were having medial tumors and were treated by wide local excision. This procedure could have interrupted the medial lymphatics, which prevented the LF of the breast from travelling to the IM LNs. Regardless of the explanation of this \u003cem\u003e\u0026quot;no LF pattern\u0026quot;\u003c/em\u003e it worth an important observation. It showed that the cases which showed LF to the 2ndLTB were the cases which showed LF to the 3ryLTB and the cases which did not show LF to the 2ryLTB were the cases which showed no flow to the 3ryLTB. According to this observation, it could reveal that the 2ndLTB could be a preliminary step that could allow LF to the other 3ryLTB. Whatever these conclusions in this study, the observed \u0026quot;no LF pattern\u0026quot; in these 2 studied cases, requires further analysis, especially by prolonging the scanning time for more than 24 hours.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eApparently, the present study shows similar findings to those of other many previous studies over decades [1,\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003cstrong\u003e, 29-30]. These previous studies and also the present study similarly showed many of the extra-axillary lymphatic territories of the breast via LSG. However, the present study differs from the previous studies in many aspects:\u003c/strong\u003e\u003c/p\u003e\n\u003col style=\"list-style-type: lower-alpha;\"\u003e\n \u003cli\u003e\u003cstrong\u003ePrevious studies were diagnosing the SLN, while the present study was not localizing the SLNs.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u0026nbsp;With the used modified technique of LSG in the present study, it allowed staging of the lymphatic territories of the breast in a sequential manner.\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u003cstrong\u003eAccordingly, the observed findings in the present study and also the similar observed findings in many previous studies, worth consideration in the following implications on the diagnoses and management of breast cancer:\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eThe IPLA LNs are the well-known 1ryLTB. Also, the IPLIM LNs are well known of the extra-axillary lymphatic territories of the breast. \u0026nbsp;However, the findings of the present study showed that the IPLIM LNs could be the most important 2ndLTB. Also, the other observed extra-axillary LTB in the present study, could be considered to be the 3ryLTB.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eThe important factors that push the LF of the breast to reach extra-axillary territories were not suggested so far. However, the blocking of the IPLA LNs could be suggested to be an important factor for directing the LF of the breast to extra-axillary LTB. This blocking was achieved either by TAD, as observed in the present study, or by their major obstruction by metastases, as observed in many studies [16, 17].\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAccording to the present study, BC recurrence after BCS and TAD should require more investigations in order to evaluate the nodal status after TAD. It should include assessment of the secondary and tertiary lymphatic territories of the breast, which may require U/S, CT, PET/CT and SLN biopsy.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eFor many decades, extra-axillary BC metastases have been described by PET/CT or even by clinical or pathological examination [2, 3, 10-23]; however, these extra-axillary lymphatic metastases from BC have not been verified to be \u003cem\u003eblood-born\u003c/em\u003e or \u003ci\u003elymph-born\u003c/i\u003e metastases. However, according to the present study and also according to other studies, which used LSG [1, 4, 9, 25-30], confirm that these reported extra-axillary metastases from BC should be lymph-born metastases, and these extra-axillary BC metastases should not be considered systemic metastases. Actually, these metastases could be considered to be a \u003ci\u003e\u0026quot;special category of regional lymphatic BC metastases\u0026quot;.\u0026nbsp;\u003c/i\u003eThis term was also described by other authorities [23].\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAccordingly, the staging system of BC should be modified to include this \u0026quot;\u003cem\u003especial category of regional lymphatic BC metastases\u0026quot;\u003c/em\u003e in the accepted staging system of BC, which is now the Tumor, Nodes, Metastases (TNM) [31]. Since the present TNM staging system of the breast reveals that BC metastases at the IPLIM LNs, with involved IPLA LNs, are now designated \u003ci\u003e\u0026quot;N3\u0026quot; and \u0026quot;Stage IIIc\u0026quot;\u003c/i\u003e [31], we can suggest that solitary BC metastases at the 3ryLTB should be designated \u003ci\u003e\u0026quot;N4\u0026quot; and \u0026quot;Stage llld\u0026quot;\u003c/i\u003e instead of being designated \u003ci\u003e\u0026quot;M+Ve\u0026quot; and \u0026quot;Stage IV\u0026quot;\u003c/i\u003e.\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eAccording to the previously suggested modifications to the TNM staging system of BC, we can suggest that the management of BC patients with solitary extra-axillary metastases should receive a local therapy (RT or surgery) in addition to the standard systemic chemotherapy. This postulation was also described by other authorities [23]. However, prospective controlled trials are needed to validate our suggested postulations in the present study.\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Conclusion","content":"\u003cp\u003e \u003cb\u003eThe LF of the breast is primarily to the IPLA LNs, which are well known to be the 1ryLTB. In the present study, BC patients with BCS and TAD were studied by modified breast LSG. These modifications forced the LF of the breast to many extra-axillary territories of the breast and also allowed staging of the LF of the breast in a sequenced manner. This study revealed that the IPLIM LNs could be the 2ndLTB. Also 3ryLTB were suggested. These observed 3ryLTB were the ipsilateral mediastinal LNs, the CLIntM LNs, and the preaortic LNs in the abdomen. According to the present study, the 2ndLTB was observed to be the essential pathway that could allow LF of the breast to the 3ryLTB. Accordingly, tumor recurrence in patients with BCS and TAD should require further assessment of their nodal status at the secondary and tertiary lymphatic territories.\u003c/b\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eThe findings of the present study, and according to other studies, suggest that extra-axillary BC metastases are lymph-born rather than blood-born metastases. Additionally, these lymph-born metastases should be considered to be a \"special category of regional lymphatic BC metastases\". Accordingly, BC metastases at 3ryLTB should be designated\u003c/b\u003e \u003cb\u003e\"N4\" and \"Stage lllD\"\u003c/b\u003e \u003cb\u003einstead of being designated\u003c/b\u003e \u003cb\u003e\"M\u0026thinsp;+\u0026thinsp;Ve\" and \"Stage IV\"\u003c/b\u003e. \u003cb\u003eAdditionally, the management of BC patients with solitary extra-axillary metastases should be managed by local therapy (RT or surgery), in addition to standard systemic chemotherapy.\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eWith the observed findings in the present study, further studies are required to confirm the presence of 3ryLTB.\u003c/b\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003col\u003e\n \u003cli\u003e\u003cstrong\u003eBreast cancer: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;BC\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eContralateral Axillary: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;CLA\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eContralateral internal mammary: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;CLIM\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eContralateral intra-mammary: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; CLIntM\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eInternal mammary: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; IM\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIpsilateral axilla: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; IPLA\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eIpsilateral internal mammary: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;IPLIM\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLymph node: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;LN\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLymph nodes: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;LNs\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLymphatic territory of the breast: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; LTB\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLymph\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;trunk: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;LT\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLymph\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;trunks: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;LTs\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eLymphoscintigraphy: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;LSG\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003ePrimary lymphatic territory of the breast: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;1ryLTB\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eRadiotherapy \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;RT\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSentinel lymph node: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;SLN\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSentinel lymph nodes: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;SLN\u003c/strong\u003e\u003cstrong\u003es\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSecondary lymphatic territory of the breast: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; 2ndLTB\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTertiary lymphatic territory of the breast: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;3ryLTB\u003c/strong\u003e\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eThe authors thank the studied patients who provided their consent which revealed the observed results.\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatements and Declarations\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eApproval statements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe procedures performed in the studied humans were accepted by the Scientific Committee of the Breast Unit of Al-Matareya Educational Hospital which was designated \u003cem\u003e\u0026quot;SCBU-MEH-GOTHI-15-3-06\u0026quot;\u003c/em\u003e. The ethical standards of this protocol were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.Data availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe datasets generated during the current study are available only from the corresponding author upon reasonable request.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions and consent for publication:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMM is the primary author. He was involved in all stages of the paper\u0026rsquo;s preparation. YS was responsible for all the work on the gamma camera. MA and BA made significant contributions to the article\u0026rsquo;s design. In combination, all the authors provided supervisory oversight, reviewed the article and gave final approval for publication.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding: declare:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe authors did not receive funding, grants, or other support from any organization for this submitted work.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe authors declare that there are no relevant financial or nonfinancial interests to disclose.\u003c/strong\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKawase, K. et al. Use of lymphoscintigraphy defines lymphatic drainage patterns before sentinel lymph node biopsy for breast cancer. \u003cem\u003eJ. Am. Coll Surg\u003c/em\u003e. \u003cstrong\u003e203(1),\u003c/strong\u003e 64-72. 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Breast Cancer\u003c/em\u003e\u003cstrong\u003e7(6),\u003c/strong\u003e 486-488 (2007). https//doi.10.3816/CBC.2007.n.006\u003cstrong\u003e.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eEstourgie, S.H., Nieweg, O.E., Vald\u0026eacute;s Olmos, R.A., Rutgers, E.J. \u0026amp; Kroon, BBR. Lymphatic Drainage Patterns from the Breast.\u003cem\u003e Annals of Surgery\u003c/em\u003e\u003cstrong\u003e239(2)\u003c/strong\u003e 232-237 2004).\u003cu\u003ehttps//doi.10.1097/01.sla.0000109156.26378.90\u003c/u\u003e.\u003c/li\u003e\n\u003cli\u003eIntra, M. et al. Second Axillary Sentinel Lymph Node Biopsy for Breast Tumor Recurrence: Experience of the European Institute of Oncology \u003cem\u003eAnn. of Surg. Oncol\u003c/em\u003e\u003cstrong\u003e22,\u003c/strong\u003e 2372-2377 (2015). \u003cu\u003ehttps//doi.\u003c/u\u003e10.1245/s10434-014-4282-5\u003cstrong\u003e.\u003c/strong\u003e\u003c/li\u003e\n\u003cli\u003eHong, J. et al. Extra-axillary sentinel node biopsy in the management of early breast cancer. \u003cem\u003eEJSO\u003c/em\u003e\u003cstrong\u003e31(9),\u003c/strong\u003e 942-948 (2005). \u003cu\u003ehttps//doi.\u003c/u\u003e10.1016/j.ejso.2005.08.003.\u003c/li\u003e\n\u003cli\u003eBourgeois, P. \u0026amp; Fr\u0026uuml;hling, J. Contralateral internal mammary node invasion in breast cancer: lymphoscintigraphic data. \u003cem\u003eBreast\u003c/em\u003e\u003cstrong\u003e 8(3\u003c/strong\u003e\u003cstrong\u003e),\u003c/strong\u003e 107-109. (1999). \u003cu\u003ehttps//doi.\u003c/u\u003e\u003cu\u003e10.1054/brst.1999.0050\u003c/u\u003e. PMID: 14965724.\u003c/li\u003e\n\u003cli\u003eMaaskant-Braat, A.J.G., de Bruijn, S.Z., Woensdregt, K., Pijpers, H, Voogd, A.C. \u0026amp; Nieuwenhuijzen, G.A.P. Lymphatic mapping after previous breast surgery. Breast \u003cstrong\u003e21(4), \u003c/strong\u003e444-448 (2012). https//doi.10.1016/j.breast.2011.10.007.\u003c/li\u003e\n\u003cli\u003eVural, G.U., Şahiner, I.,Demirtaş, S., Efet\u0026uuml;rk, H., \u0026amp; Demirel, B.B. Sentinel Lymph Node Detection in Contralateral Axilla at Initial Presentation of a Breast Cancer Patient: \u003cem\u003eMol. Imag. Radionucl. Ther\u003c/em\u003e. \u003cstrong\u003e24(2),\u003c/strong\u003e 90\u0026ndash;93 (2015). \u003cu\u003ehttps//doi.\u003c/u\u003e10.4274/mirt.91300.\u003c/li\u003e\n\u003cli\u003eAmin, M.B. et al. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more \u0026quot;personalized\u0026quot; approach to cancer staging. \u003cem\u003eCA Cancer J. Clin\u003c/em\u003e. \u003cstrong\u003e67(2),\u003c/strong\u003e 93-99 (2017). \u003cu\u003ehttps//doi.10.3322/caac.21388\u003c/u\u003e.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1: Results of 11 cases with LSG images at different time intervals (1-8 hours).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 53.9088%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Imaging Time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 18.4039%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 12.3779%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2-4 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15.3094%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6-8 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 53.9088%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Anatomical Sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.18893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.18893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 53.9088%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Periareolar Injection Sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.18893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.18893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 53.9088%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Ipsilateral Axillary LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.18893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.18893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 53.9088%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Contralateral Internal Mammary LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7492%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.18893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.18893%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.65472%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; LNs: Lymph nodes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; Hr: Hour\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; +Ve: Positive\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp; -Ve: Negative\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2: Results of 9 cases with LSG images at different time intervals (1-8 hours).\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv align=\"left\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 52.3654%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Imaging Time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 18.4339%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 13.8662%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2-4 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 15.3344%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6-8 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 52.3654%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Anatomical Sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.19902%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 52.3654%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Periareolar Injection Sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.19902%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 52.3654%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Ipsilateral Axillary LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.19902%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 52.3654%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Contralateral Internal-mammary LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.19902%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 52.3654%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Ipsilateral Mediastinal LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.19902%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 52.3654%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Ipsilateral Intra-Mammary LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.19902%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 52.3654%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Preaortic LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10.7667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 6.19902%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 7.66721%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;LNs: Lymph nodes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Hr: Hour\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e+Ve: Positive\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e-Ve: Negative\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3: Results of 2 cases with LSG images at different time intervals (1-24 hours).\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Imaging Time\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2-4 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6-8 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e24 Hr\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; Anatomical Sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e+Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-Ve\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;Periareolar Injection Sites\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIpsilateral Axillary LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eContralateral Internal Mammary LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIpsilateral Mediastinal LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIpsilateral Intramammary LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePreaortic LNs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 47px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;LNs: Lymph nodes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Hr: Hour\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;+Ve: Positive\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;-Ve: Negative\u003c/strong\u003e\u003c/p\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 Conserving Surgery, Breast Lymphoscintigraphy, Tertiary Lymphatic Territories for the Breast, Sequencing of Breast Lymph Flow","lastPublishedDoi":"10.21203/rs.3.rs-6771010/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6771010/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLymphoscintigraphy (LSG) of the breast was mainly use for the diagnoses of the sentinel lymph node (SLN) of the breast. With breast LSG, the SLN was mainly observed at the ipsilateral axillary (IPLA) lymph nodes (LNs). However, many SLNs were observed at many extra-axillary lymphatic territories of the breast (LTB).\u003c/p\u003e \u003cp\u003eThis study included female patients with stage II breast cancer (BC). They underwent breast-conserving surgery. Studied Patients underwent modified techniques for breast LSG which were not aiming to diagnose the SLN. They were aiming to stage the LF of the breast in a sequential manner.\u003c/p\u003e \u003cp\u003eAfter Covering the injection sites, the LF of the breast appeared at the ipsilateral internal mammary (IPLIM) LNs. When the observed IPLIM were further covered by lead shields, breast LF appeared at other three sites which were: mediastinal LNs, contralateral intra-mammary (CLIntM) LNs and pre-aortic LNs in the abdomen.\u003c/p\u003e \u003cp\u003eSince the IPLA LNs are the primary LTB, the observed IPLIM LNs could be the secondary LTB. In addition, the mediastinal LNs, the CLIntM LNs and The pre-aortic LNs could be tertiary LTB. Accordingly, the present study suggested modifications for the staging of the TNM system of the breast and also the management of BC.\u003c/p\u003e","manuscriptTitle":"Sequencing of the lymphatic territories of the breast: Possibility of tertiary lymphatic territories after breast- conserving surgery: A preliminary study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-04 05:40:02","doi":"10.21203/rs.3.rs-6771010/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":"5a2aed15-dc3a-4601-9457-cd21bd06d824","owner":[],"postedDate":"July 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":50845779,"name":"Biological sciences/Cancer"},{"id":50845780,"name":"Health sciences/Anatomy"},{"id":50845781,"name":"Health sciences/Medical research"},{"id":50845782,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2026-04-20T15:11:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-04 05:40:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6771010","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6771010","identity":"rs-6771010","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}