Analysis of prognostic and predictive factors of isolated chest wall recurrence in breast cancer after mastectomy

Analysis of prognostic and predictive factors of isolated chest wall recurrence in breast cancer after mastectomy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Analysis of prognostic and predictive factors of isolated chest wall recurrence in breast cancer after mastectomy Yanrong Wang, Ming Gao, Huan Yan, Junhao You, Lijuan Ding, Guanghai Dai, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4577325/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 Objective: To investigate the clinical features, molecular subtypes, and factors influencing metastasis in patients with breast cancer chest wall metastasis. Methods: We collected the clinical data of patients who developed isolated chest wall metastasis following radical surgery for breast cancer. The molecular subtypes of the primary lesions and secondary biopsy lesions in patients with chest wall metastasis were analyzed and summarized. The disease-free survival (DFS) after breast cancer surgery and its influencing factors were also documented. Results: Of the 99 cases of isolated chest wall recurrence included in our study, DFS varied from 1 to 264 months, with a median DFS of 36 months. The 3-year disease-free survival rate was 44.6%, while the 5-year rate was 24.2%. Molecular subtype changes occurred in a total of 28 cases before and after metastasis, accounting for 34% of the cases. COX multivariate analysis revealed that pathological type, surgical staging, postoperative expression status of ER (estrogen receptor), PR (progesterone receptor), Ki-67, HER-2 (human epidermal growth factor receptor-2), and the receipt of adjuvant chemotherapy after surgery were independent factors affecting chest wall recurrence and metastasis. Conclusion: Local recurrence after breast cancer surgery increases the risk of distant metastasis. Identifying high-risk factors for recurrence enables the tailoring of individualized comprehensive treatment plans based on the patient's condition, thus reducing the risk of local recurrence and improving survival outcomes. breast neoplasms isolated chest wall recurrence treatment prognosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction Breast cancer is one of the most common malignant tumors in women worldwide, and surgery is the preferred treatment for early breast cancer. After radical mastectomy, about 5%-30% of patients will have a locoregional recurrence (LRR), while 2/3 show isolated locoregional recurrence (ILRR) without distant metastasis[1–3]. The chest wall is the most common site of locoregional recurrence in early-stage breast cancer after mastectomy. Some studies have found that the prognosis of isolated chest wall recurrence (ICWR) after breast cancer surgery is better than that of isolated locoregional lymph node metastasis. A considerable proportion of patients with isolated chest wall recurrence after breast cancer surgery can survive for a long time. Therefore, one of the keys to improving the survival rate of breast cancer patients is how to detect and effectively prevent chest wall recurrence[4]. Previous studies have suggested that the results of locoregional and systemic therapy for ILRR after mastectomy may be influenced by a variety of clinicopathological variables, including nodal status at original diagnosis, hormone receptor status, Her-2 expression, and ILRR site[5,6]. ICWR patients are usually treated with a variety of therapies, including resection of recurrent tumors, radiotherapy, and systemic therapy[2,4,7,8]. However, there is a debate about the optimal radiotherapy dose for isolated LRR, with most advocating irradiation of all local and regional areas, while others recommend selective irradiation of the chest wall and selected lymph node areas, or only local radiotherapy. The value of preventive regional nodal Irradiation (RNI) for ICWR patients has not been fully evaluated, and research results are affected by the study population or study duration. In addition, postoperative systemic therapy not only reduces the risk of LRR but also reduces the risk of distant metastasis (DM). The purpose of this study was to collect and analyze clinical data of patients with isolated chest wall recurrence who had undergone breast cancer surgery in PLA General Hospital, and to explore the relationship between the timing of chest wall recurrence in such patients and influencing factors in order to facilitate the effective implementation of clinical prevention strategies and rational selection of treatment plans, thereby improving patients’ prognosis. 2. Materials and methods 2.1 General information From January 2000 to January 2020, a total of 99 female patients with first-episode chest wall metastasis after breast cancer surgery were treated at the First Medical Center and the Eighth Medical Center of the Chinese People's Liberation Army General Hospital. Inclusion criteria: (1) did not receive any neoadjuvant chemoradiotherapy before surgery; (2) postoperative TNM staging: I, II, III; (3) the ipsilateral chest wall was the first recurrence site; (4) pathological or Imaging confirmed recurrence; (5) no regional lymph node recurrence within 1 month of recurrence, and no distant metastasis within 3 months. Distant metastasis concurrent with the diagnosis of ICWR within 3 months were excluded. 2.2 Evaluation indicators: Statistical clinical indicators include age, surgical method, pathological type, postoperative TNM staging, grading, ER, PR, Her-2, Ki-67 expression, molecular typing, postoperative adjuvant chemotherapy, whether Radiotherapy, endocrine therapy, or targeted therapy. Disease-free survival (DFS) was defined as the time from the time of radical surgery to the time of chest wall metastasis or death from other causes in breast cancer patients. 2.3 Follow-up: The patients were followed up by visiting the hospital for re-examination, reviewing previous electronic records, and telephone return visits. The follow-up cut-off time was June 30, 2022 with a median follow-up time of 92 months. 2.4 Statistical methods R version 4.2.3 was used for statistical analysis of survival and related factors. Survival analysis was performed using the Kaplan-Meier method. The comparison of survival curves between groups was performed using the Log-Rank test. Through Cox proportional hazard modeling, univariate and multivariate analyses were carried out to evaluate the predictive features connected to PFS. The following variables were chosen for multivariate analysis: age at initial diagnosis, pathological type, surgery method, TNM staging, postoperative T staging, postoperative N staging, histological grade, ER expression, PR expression, Her-2, Ki-67 rate, postoperative adjuvant chemotherapy, postoperative endocrine therapy, postoperative radiotherapy. P < 0.05 was considered statistically significant. 3. Results 3.1 Basic characteristics of patients The age at first diagnosis of breast cancer was 28–76 years old, with a median age of 53 years. The clinical staging of primary tumors was based on the AJCC TNM staging criteria for breast cancer (seventh edition, 2010), including 42 cases of stage I-II, 27 cases of stage III, and 30 cases of the unknown stage. Pathological classification: 61 cases of invasive ductal carcinoma, 7 cases of invasive lobular carcinoma, 2 cases of medullary carcinoma, 21 cases of invasive carcinoma, and 8 cases of other pathological types. 3.2 Molecular typing and treatment of primary tumors Among the 99 patients, 16 underwent breast-conserving surgery, 81 underwent a modified radical mastectomy, and 2 had unknown surgical procedures. According to the expression of ER, PR, and HER-2, the molecular typing is classified; HER-2 positive definition: immunohistochemical 3 + or + 2 and FISH positive. The positive threshold for ER and PR was set as ≥ 1%. Hormone receptor ER positive: 61 cases, negative 38 cases, unknown; PR positive in 53 cases, negative in 46 cases. HER-2 positive: 32 cases, 50 negative cases, and 17 unknown cases. Excluding 17 patients with unknown molecular type, the proportion of 82 patients with primary tumor molecular type: Luminal type: 36 cases (43.9%), triple-negative type: 14 cases (17.1%), her-2 overexpression type: 32 cases (39%). As shown in Table 1 . Treatment regimens includes chemotherapy, endocrine therapy, targeted therapy, and radiotherapy. Postoperative chemotherapy: 85 cases received conventional postoperative chemotherapy, and the chemotherapy regimens were mainly anthracyclines or taxanes. Endocrine therapy: 40 cases received adjuvant endocrine therapy after the operation, and 59 cases don’t receive endocrine therapy. Postoperative radiotherapy: radiotherapy was performed in 41 cases, and 58 cases were not performed. Among the 32 her-2 positive patients, 9 were using Herceptin, 19 were not, and 4 were unknown. Table 1 Clinical baseline characteristics of 99 breast cancer patients with chest wall recurrence after surgery Characteristics No. of patients (%) Age at initial diagnosis (years) ≥ 50 59(59.6) < 50 40(40.4) Pathological type Invasive ductal carcinoma 62(62.6) Invasive lobular carcinoma 9(9.1) medullary carcinoma 2(2.0) Other invasive carcinomas 21(21.2) Other pathological types 5(5.1) Surgery method radical mastectomy 81(81.8) breast-conserving surgery 16(16.2) Unknown 2(2.0) TNM staging I-II 42(42.4) III 27(27.3) Unknown 30(30.3) Postoperative T staging T1-T2 62(62.6) T3 13(13.1) Unknown 24(24.2) Postoperative N staging N0-1 12(12.1) N2-3 60(60.6) Unknown 27(27.3) Histological grade I-II 39(39.4) III 43(43.4) Unknown 17(17.2) ER expression Positive 61(61.6) Negative 38(38.4) PR expression Positive 53(53.5) Negative 46(46.5) Her-2 Positive 32(32.3) Negative 50(50.5) Unknown 17(17.2) Ki-67 rate ≥ 14 64(64.6) < 14 22(22.3) Unknown 13(13.1) Postoperative adjuvant chemotherapy Yes 85 (85.9) No 14(14.1) Postoperative endocrine therapy Yes 40(40.4) No 59(59.6) Postoperative radiotherapy Yes 41(41.4) No 58(58.6) Postoperative targeted therapy Yes 9(9.1) No 86(86.9) Unknown 4(4.0) 3.3 Molecular typing and DFS of secondary pathology after chest wall metastasis All patients with chest wall metastasis underwent secondary biopsy, and the metastases were classified by molecular typing again, and disease-free survival (DFS) was calculated. Excluding 16 patients with unknown molecular type, the proportion of the molecular type of recurrence and metastasis in 83 patients: Luminal type: 34 cases (40.9%), triple-negative type: 16 cases (19.3%), her-2 overexpression type: 33 cases example (39.8%). Time to chest wall metastasis DFS: 1-264 months, the median time to recurrence: 36 months. 3.4 Conversion rate of molecular typing of secondary pathology after chest wall metastasis After chest wall metastasis, a total of 83 patients underwent secondary biopsy, Luminal type was converted to her-2 positive type: 8 cases, Luminal type was converted to triple negative type: 3 cases, her-2 positive was converted to negative type: 5 cases, her-2 negative was converted to positive type: 9 cases, the triple-negative type was converted to her-2 positive type: 1 case, the triple-negative type was converted to Luminal type: 2 cases. A total of 28 cases, accounting for 34%, had changes in molecular typing before and after metastasis. Of these, 21 (75%) had a HER-2 positive or triple-negative transition, which also represents a worse prognosis. 3.5 Univariate and multivariate analysis of the relationship between clinical characteristics of primary tumors and DFS The survival analysis results of different postoperative treatments are shown in Fig. 1 , Fig. 2 , and Fig. 3 . As shown in Fig. 4 , after univariate analysis of the basic clinical characteristics of breast cancer patients, it was found that local chest wall recurrence after breast cancer surgery was not related to the surgical method of patients and TNM staging. There is a close relationship between the local chest wall recurrence and age, pathological type, postoperative T staging, postoperative N staging, postoperative grading, ER, PR, Her-2, Ki-67 expression, postoperative chemotherapy, endocrine therapy, radiotherapy, and targeted therapy. Further COX multivariate analysis results showed that: pathological type, surgical grade, postoperative ER, PR, Ki-67, her-2 expression, and postoperative adjuvant chemotherapy were independent influencing factors for chest wall recurrence and metastasis. See Fig. 5 . 4. Discussion Local recurrence after radical mastectomy for breast cancer refers to the recurrence of the ipsilateral chest wall or (and) local lymph nodes after surgery. The recurrence rate is about 5%-30%, of which chest wall recurrence is the most common, accounting for 50%-94%. Local recurrence is a sign of other distant metastases in breast cancer and is an important factor affecting survival after breast cancer surgery[2,7]. Chest wall metastasis can occur at any time after breast cancer surgery. Among the 99 patients with isolated chest wall recurrence collected in this study, the DFS was 1-264 months, the median DFS was 36 months, and the 3-year disease-free survival rate was 44.6%, 5 years was 24.2%. According to literature reports, local recurrence is the mainstay within 2–3 years. After recurrence, 60%-80% of patients develop distant metastases, including lung, liver, and bone metastases[9]. It is of great significance to analyze the risk factors of local recurrence in breast cancer patients and take corresponding preventive measures to improve the prognosis of breast cancer patients. This article is the most comprehensive study to collect data on isolated chest wall recurrence after breast cancer surgery and secondary biopsy after recurrence. Relevant studies have shown that the recurrence and metastasis of breast cancer after surgery are related to a variety of factors. Age, tumor size, lymph node metastasis, pathological type, hormone receptor status and her-2 expression status, postoperative staging, and postoperative treatment methods may be related to the recurrence and metastasis of breast cancer after surgery[10,11]. The histological grade is closely related to tumor invasion and metastasis, and is also positively related to visceral metastasis, the higher the grade, the higher the degree of malignancy, and the earlier the local invasion and distant metastasis. Primary tumor size and local lymph node metastasis are the two main factors affecting tumor TNM staging. Most studies have shown that the larger the tumor, the more lymph node metastasis, the higher the risk of local recurrence and distant metastasis, and the worse the prognosis. The size of the tumor indirectly reflects its biological characteristics, and lymph node metastasis is one of the most common ways of tumor metastasis. Therefore, the size of the tumor and the number of lymph node metastasis are closely related to the postoperative local recurrence of breast cancer[12,13]. The results of the univariate analysis in this study found that age, postoperative T stage, and postoperative N stage were associated with DFS, but multivariate analysis results showed that they were not independent risk factors for DFS, but tissue grade was an independent risk factor for DFS. More and more researchers are devoted to the molecular biology research of breast cancer recurrence and metastasis, hoping to clarify the molecular mechanism of breast cancer recurrence and metastasis from the perspective of molecular biology, so as to develop drugs that can effectively inhibit breast cancer recurrence and metastasis. At present, the molecular biological markers associated with breast cancer recurrence mainly include ER, PR, Ki-67, Her-2, and so on. Studies have found that patients with hormone receptor-positive cells have a high degree of cell differentiation and a low degree of malignancy [14–16]. ER and PR positivity are one of important protective factors for the recurrence and prognosis of breast cancer patients, and the risk of recurrence and metastasis of breast cancer patients receiving endocrine therapy is significantly reduced [15]. Ki-67 is an important regulator of the cell cycle and cell proliferation. Protein antigen, the higher the Ki-67, the faster the cell proliferation, the higher the degree of malignancy, and the worse the prognosis [16]. Studies have found that the expression product of the oncogene Her-2 is a key factor regulating tumor growth and plays an important role in the occurrence, development, metastasis, and prognosis of breast cancer [15]. Faneyte et al. found that the 5-year survival rate of patients with overexpression of her-2 was significantly lower than that of patients with negative expression of her-2[17]. In addition, patients with overexpression of her-2 were not sensitive to conventional adjuvant therapy and were more likely to develop local lymph node metastasis, which would develop a poor prognosis. The results of multivariate analysis in this study showed that positive hormone receptor expression, ki-67 ≥ 14, and her-2 positive were independent risk factors for chest wall recurrence. In recent years, breast cancer tends to be younger. Young patients have stronger tumor invasiveness, faster disease progression, and earlier local recurrence and distant metastasis. Some studies believe that younger age is an independent risk factor for breast cancer recurrence and metastasis after surgery. Reports on the relationship between local recurrence of cancer are inconsistent[18–21]. This study divided age into ≥ 50-year-old group and < 50-year-old group. Univariate analysis showed that the DFS of different age groups was statistically different, but multivariate analysis showed that age was not an independent risk factor for chest wall recurrence. The main methods of breast cancer treatment include surgery, chemotherapy, radiotherapy, targeted therapy, endocrine therapy, etc. Studies have found that reasonable and effective adjuvant therapy after radical mastectomy can significantly improve the 5-year survival rate of patients. In terms of postoperative adjuvant chemotherapy, adjuvant chemotherapy after breast cancer surgery can significantly prolong the DFS of local recurrence, especially for hormone receptor-negative patient[22,23]. Another study confirmed that postoperative adjuvant endocrine therapy can significantly reduce the rate of local recurrence and distant metastasis[24]. Regarding the sequence of postoperative adjuvant chemotherapy and endocrine therapy, it is recommended to complete adjuvant chemotherapy before starting endocrine therapy[22,23]. In terms of local radiotherapy, many studies have confirmed that it has a significant effect on controlling the local recurrence rate after breast cancer surgery and improving long-term survival[24,25], and it is one of the main methods for postoperative local treatment of breast cancer, especially for patients with ≥ 4 positive axillary lymph nodes[9,26,27]. The univariate analysis results of this study showed that the comprehensive treatment mode of postoperative adjuvant chemotherapy, endocrine therapy, and radiotherapy can significantly prolong the DFS of chest wall metastasis after breast cancer surgery. Further COX multivariate analysis showed that adjuvant chemotherapy was an independent protective factor for chest wall metastasis after breast cancer surgery. Targeted therapy was not included in this study's univariate and multivariate analysis because there were only 9 patients who received targeted therapy in the collected patients, and the number of cases was unbalanced with an obvious bias. This study had several limitations. Firstly, the clinical and molecular factors were assessed retrospectively from medical records, which may have introduced errors or missing data. Additionally, the study did not perform a rigorous assessment of inter-rater reliability to ensure consistency in data collection and interpretation. Lastly, the study only analyzed DFS as the primary outcome, and did not assess other clinically relevant outcomes, such as overall survival or quality of life. Therefore, the study may not provide a comprehensive understanding of the impact of chest wall metastasis on breast cancer patients. while this study provides valuable insights into the clinical and molecular factors associated with chest wall metastasis in breast cancer patients, the results should be interpreted with caution due to the limitations discussed above. Further studies with larger sample sizes, more diverse patient populations, and longer follow-up periods are needed to validate these findings and provide a more comprehensive understanding of the impact of chest wall metastasis on breast cancer patients. In conclusion, this study showed that surgical grade, postoperative ER, PR, Ki-67, HER-2 expression, and postoperative adjuvant chemotherapy were independent risk factors affecting the local recurrence of breast cancer after surgery. As local recurrence after breast cancer surgery increases the risk of distant metastasis, therefore, identifying the risk factors of recurrence and selecting individualized comprehensive treatment for patients is crucial to reduce the risk of postoperative local recurrence, improve prognosis, and enhance survival. Declarations Ethics statement Approval of the research protocol by an institutional reviewer board: The study protocol was approved by the Ethics Committee of PLA General Hospital. Informed consent: Informed consent was obtained from the patients for use of their data for experimentation. Conflicts of interest: All authors declare no conflict of interest. Funding This study received no specific funding from public, commercial, or not-for-profit funding entities Author Contribution Yanrong Wang: Data curation, Formal analysis, Investigation, Validation, Writing – original draft, Writing – review & editing. Ming Gao: Investigation, Validation, Data curation. Yan Huan: Investigation, Validation. Junhao You: Investigation, Validation. Lijuan Ding: Investigation, Validation,. Guanghai Dai: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Writing – review & editing. Xia Zhang: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Writing – review & editing. Acknowledgement GD contributed to study design and conception; XZ was responsible for the conduct and supervision of the study; YW, HY and MG were involved in data collection; YW and HY contributed to the statistical analysis; JY and LD made telephone follow-up; YW drafted the manuscript and polished the language. All authors have read and approved the final manuscript. Data availability statement The relevant data supporting the conclusions of this article will be available by contacting the corresponding authors upon reasonable request. 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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-4577325","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":321936852,"identity":"35c1d629-ef4d-4470-8a6f-c9c476b39373","order_by":0,"name":"Yanrong Wang","email":"","orcid":"","institution":"First medical center of Chinese PLA general hospital","correspondingAuthor":false,"prefix":"","firstName":"Yanrong","middleName":"","lastName":"Wang","suffix":""},{"id":321936853,"identity":"9619f829-b96b-4faa-8f92-569d11ae56bc","order_by":1,"name":"Ming Gao","email":"","orcid":"","institution":"Fifth medical center of Chinese PLA general hospital","correspondingAuthor":false,"prefix":"","firstName":"Ming","middleName":"","lastName":"Gao","suffix":""},{"id":321936854,"identity":"69676ab3-30a2-48f6-8654-fa4bb1cf21d2","order_by":2,"name":"Huan Yan","email":"","orcid":"","institution":"Fifth medical center of Chinese PLA general hospital","correspondingAuthor":false,"prefix":"","firstName":"Huan","middleName":"","lastName":"Yan","suffix":""},{"id":321936855,"identity":"a4fa62ee-be9b-4e6a-8f29-14d949674754","order_by":3,"name":"Junhao You","email":"","orcid":"","institution":"Hainan hospital of Chinese PLA general hospital","correspondingAuthor":false,"prefix":"","firstName":"Junhao","middleName":"","lastName":"You","suffix":""},{"id":321936856,"identity":"a3082ca6-5300-4568-bdfc-3fba0994a5ee","order_by":4,"name":"Lijuan Ding","email":"","orcid":"","institution":"Hainan hospital of Chinese PLA general hospital","correspondingAuthor":false,"prefix":"","firstName":"Lijuan","middleName":"","lastName":"Ding","suffix":""},{"id":321936857,"identity":"f716764c-aa58-4600-b970-2bfe3f6885fa","order_by":5,"name":"Guanghai Dai","email":"","orcid":"","institution":"Fifth medical center of Chinese PLA general hospital","correspondingAuthor":false,"prefix":"","firstName":"Guanghai","middleName":"","lastName":"Dai","suffix":""},{"id":321936858,"identity":"8e1e4936-065d-4dcb-a620-b01a18445129","order_by":6,"name":"Xia Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA10lEQVRIiWNgGAWjYFAC5gOHf/6x4bFvb2x8+IE4LWyJjxkb0mQMeA43G0sQp4VH2Zix4bCNgUR6mwAPMRrkZ+SwSRfuYOYxl3zYxiDBYCen20BAC2PP2WPSM8+w8VjOTmx7UMCQbGx2gIAWZva+NAkeNh4ehtuJ7QYSDAcStxHSwsbMYwbUIsHDcPNgG5AkQgsPe4+xMW+bAY/BDUYitUjwHEt8OONMAo9kTyIwkA2I8Iv8jOQDBz5U/LfnZz/+8OGHCjs5glrQgAFpykfBKBgFo2AU4AAAKWtAELlDsm0AAAAASUVORK5CYII=","orcid":"","institution":"Fifth medical center of Chinese PLA general hospital","correspondingAuthor":true,"prefix":"","firstName":"Xia","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-06-13 15:51:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4577325/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4577325/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60435346,"identity":"3a060863-ba73-4209-b7ab-0ab62812dac9","added_by":"auto","created_at":"2024-07-16 17:21:43","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":28613,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe Kaplain-Meier curves for Postoperative adjuvant chemotherapy.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4577325/v1/0b8a2ce016322aac93d4cc0b.png"},{"id":60435349,"identity":"471405c0-de8a-4a58-b80d-8be9cb8d4a65","added_by":"auto","created_at":"2024-07-16 17:21:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":36464,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe Kaplain-Meier curves for Postoperative radiotherapy.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4577325/v1/71e40ceb03421917a82c0f73.png"},{"id":60435347,"identity":"499055f6-9e9f-416b-acff-350aa0975357","added_by":"auto","created_at":"2024-07-16 17:21:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":36899,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe Kaplain-Meier curves for Postoperative endocrine therapy.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4577325/v1/9f3923c4114be34b8c8d78d1.png"},{"id":60435348,"identity":"7ac867d9-0183-448f-b1c1-1aa78c78ee48","added_by":"auto","created_at":"2024-07-16 17:21:43","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":190676,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eUnivariate analysis of 99 breast cancer patients with chest wall recurrence after surgery\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4577325/v1/d62d3f70b3c3b41f873a0de9.jpg"},{"id":60435350,"identity":"a195e05f-85de-4ccf-9740-c94eb5764f20","added_by":"auto","created_at":"2024-07-16 17:21:44","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":166407,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMultivariate analysis of 99 breast cancer patients with chest wall recurrence after surgery\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4577325/v1/2def5b7104615c98990a7105.jpg"},{"id":63713223,"identity":"f8e84137-739c-4c20-82a4-5fb945ae6c5f","added_by":"auto","created_at":"2024-09-01 03:35:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1265077,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4577325/v1/5e9b7eae-617d-4aa1-8659-ebd555b05cac.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Analysis of prognostic and predictive factors of isolated chest wall recurrence in breast cancer after mastectomy","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eBreast cancer is one of the most common malignant tumors in women worldwide, and surgery is the preferred treatment for early breast cancer. After radical mastectomy, about 5%-30% of patients will have a locoregional recurrence (LRR), while 2/3 show isolated locoregional recurrence (ILRR) without distant metastasis[1\u0026ndash;3]. The chest wall is the most common site of locoregional recurrence in early-stage breast cancer after mastectomy. Some studies have found that the prognosis of isolated chest wall recurrence (ICWR) after breast cancer surgery is better than that of isolated locoregional lymph node metastasis. A considerable proportion of patients with isolated chest wall recurrence after breast cancer surgery can survive for a long time. Therefore, one of the keys to improving the survival rate of breast cancer patients is how to detect and effectively prevent chest wall recurrence[4]. Previous studies have suggested that the results of locoregional and systemic therapy for ILRR after mastectomy may be influenced by a variety of clinicopathological variables, including nodal status at original diagnosis, hormone receptor status, Her-2 expression, and ILRR site[5,6]. ICWR patients are usually treated with a variety of therapies, including resection of recurrent tumors, radiotherapy, and systemic therapy[2,4,7,8]. However, there is a debate about the optimal radiotherapy dose for isolated LRR, with most advocating irradiation of all local and regional areas, while others recommend selective irradiation of the chest wall and selected lymph node areas, or only local radiotherapy. The value of preventive regional nodal Irradiation (RNI) for ICWR patients has not been fully evaluated, and research results are affected by the study population or study duration. In addition, postoperative systemic therapy not only reduces the risk of LRR but also reduces the risk of distant metastasis (DM).\u003c/p\u003e \u003cp\u003eThe purpose of this study was to collect and analyze clinical data of patients with isolated chest wall recurrence who had undergone breast cancer surgery in PLA General Hospital, and to explore the relationship between the timing of chest wall recurrence in such patients and influencing factors in order to facilitate the effective implementation of clinical prevention strategies and rational selection of treatment plans, thereby improving patients\u0026rsquo; prognosis.\u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 General information\u003c/h2\u003e \u003cp\u003eFrom January 2000 to January 2020, a total of 99 female patients with first-episode chest wall metastasis after breast cancer surgery were treated at the First Medical Center and the Eighth Medical Center of the Chinese People's Liberation Army General Hospital. Inclusion criteria: (1) did not receive any neoadjuvant chemoradiotherapy before surgery; (2) postoperative TNM staging: I, II, III; (3) the ipsilateral chest wall was the first recurrence site; (4) pathological or Imaging confirmed recurrence; (5) no regional lymph node recurrence within 1 month of recurrence, and no distant metastasis within 3 months. Distant metastasis concurrent with the diagnosis of ICWR within 3 months were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Evaluation indicators:\u003c/h2\u003e \u003cp\u003eStatistical clinical indicators include age, surgical method, pathological type, postoperative TNM staging, grading, ER, PR, Her-2, Ki-67 expression, molecular typing, postoperative adjuvant chemotherapy, whether Radiotherapy, endocrine therapy, or targeted therapy. Disease-free survival (DFS) was defined as the time from the time of radical surgery to the time of chest wall metastasis or death from other causes in breast cancer patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Follow-up:\u003c/h2\u003e \u003cp\u003eThe patients were followed up by visiting the hospital for re-examination, reviewing previous electronic records, and telephone return visits. The follow-up cut-off time was June 30, 2022 with a median follow-up time of 92 months.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Statistical methods\u003c/h2\u003e \u003cp\u003eR version 4.2.3 was used for statistical analysis of survival and related factors. Survival analysis was performed using the Kaplan-Meier method. The comparison of survival curves between groups was performed using the Log-Rank test. Through Cox proportional hazard modeling, univariate and multivariate analyses were carried out to evaluate the predictive features connected to PFS. The following variables were chosen for multivariate analysis: age at initial diagnosis, pathological type, surgery method, TNM staging, postoperative T staging, postoperative N staging, histological grade, ER expression, PR expression, Her-2, Ki-67 rate, postoperative adjuvant chemotherapy, postoperative endocrine therapy, postoperative radiotherapy. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Basic characteristics of patients\u003c/h2\u003e \u003cp\u003eThe age at first diagnosis of breast cancer was 28\u0026ndash;76 years old, with a median age of 53 years. The clinical staging of primary tumors was based on the AJCC TNM staging criteria for breast cancer (seventh edition, 2010), including 42 cases of stage I-II, 27 cases of stage III, and 30 cases of the unknown stage. Pathological classification: 61 cases of invasive ductal carcinoma, 7 cases of invasive lobular carcinoma, 2 cases of medullary carcinoma, 21 cases of invasive carcinoma, and 8 cases of other pathological types.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Molecular typing and treatment of primary tumors\u003c/h2\u003e \u003cp\u003eAmong the 99 patients, 16 underwent breast-conserving surgery, 81 underwent a modified radical mastectomy, and 2 had unknown surgical procedures. According to the expression of ER, PR, and HER-2, the molecular typing is classified; HER-2 positive definition: immunohistochemical 3\u0026thinsp;+\u0026thinsp;or +\u0026thinsp;2 and FISH positive. The positive threshold for ER and PR was set as \u0026ge;\u0026thinsp;1%. Hormone receptor ER positive: 61 cases, negative 38 cases, unknown; PR positive in 53 cases, negative in 46 cases. HER-2 positive: 32 cases, 50 negative cases, and 17 unknown cases. Excluding 17 patients with unknown molecular type, the proportion of 82 patients with primary tumor molecular type: Luminal type: 36 cases (43.9%), triple-negative type: 14 cases (17.1%), her-2 overexpression type: 32 cases (39%). As shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Treatment regimens includes chemotherapy, endocrine therapy, targeted therapy, and radiotherapy. Postoperative chemotherapy: 85 cases received conventional postoperative chemotherapy, and the chemotherapy regimens were mainly anthracyclines or taxanes. Endocrine therapy: 40 cases received adjuvant endocrine therapy after the operation, and 59 cases don\u0026rsquo;t receive endocrine therapy. Postoperative radiotherapy: radiotherapy was performed in 41 cases, and 58 cases were not performed. Among the 32 her-2 positive patients, 9 were using Herceptin, 19 were not, and 4 were unknown.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical baseline characteristics of 99 breast cancer patients with chest wall recurrence after surgery\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eNo. of patients (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eAge at initial diagnosis (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59(59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40(40.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathological type\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive ductal carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62(62.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInvasive lobular carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emedullary carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2(2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther invasive carcinomas\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21(21.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther pathological types\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5(5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgery method\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eradical mastectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e81(81.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ebreast-conserving surgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16(16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2(2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTNM staging\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42(42.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27(27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30(30.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative T staging\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT1-T2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62(62.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24(24.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative N staging\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN0-1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12(12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN2-3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60(60.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27(27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistological grade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39(39.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43(43.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17(17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eER expression\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61(61.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38(38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePR expression\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53(53.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46(46.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHer-2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32(32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50(50.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17(17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eKi-67 rate\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64(64.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22(22.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13(13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative adjuvant chemotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e85 (85.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14(14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative endocrine therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40(40.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e59(59.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative radiotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e41(41.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58(58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePostoperative targeted therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9(9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86(86.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4(4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Molecular typing and DFS of secondary pathology after chest wall metastasis\u003c/h2\u003e \u003cp\u003eAll patients with chest wall metastasis underwent secondary biopsy, and the metastases were classified by molecular typing again, and disease-free survival (DFS) was calculated. Excluding 16 patients with unknown molecular type, the proportion of the molecular type of recurrence and metastasis in 83 patients: Luminal type: 34 cases (40.9%), triple-negative type: 16 cases (19.3%), her-2 overexpression type: 33 cases example (39.8%). Time to chest wall metastasis DFS: 1-264 months, the median time to recurrence: 36 months.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Conversion rate of molecular typing of secondary pathology after chest wall metastasis\u003c/h2\u003e \u003cp\u003eAfter chest wall metastasis, a total of 83 patients underwent secondary biopsy, Luminal type was converted to her-2 positive type: 8 cases, Luminal type was converted to triple negative type: 3 cases, her-2 positive was converted to negative type: 5 cases, her-2 negative was converted to positive type: 9 cases, the triple-negative type was converted to her-2 positive type: 1 case, the triple-negative type was converted to Luminal type: 2 cases. A total of 28 cases, accounting for 34%, had changes in molecular typing before and after metastasis. Of these, 21 (75%) had a HER-2 positive or triple-negative transition, which also represents a worse prognosis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Univariate and multivariate analysis of the relationship between clinical characteristics of primary tumors and DFS\u003c/h2\u003e \u003cp\u003eThe survival analysis results of different postoperative treatments are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cb\u003eand\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, after univariate analysis of the basic clinical characteristics of breast cancer patients, it was found that local chest wall recurrence after breast cancer surgery was not related to the surgical method of patients and TNM staging. There is a close relationship between the local chest wall recurrence and age, pathological type, postoperative T staging, postoperative N staging, postoperative grading, ER, PR, Her-2, Ki-67 expression, postoperative chemotherapy, endocrine therapy, radiotherapy, and targeted therapy. Further COX multivariate analysis results showed that: pathological type, surgical grade, postoperative ER, PR, Ki-67, her-2 expression, and postoperative adjuvant chemotherapy were independent influencing factors for chest wall recurrence and metastasis. See Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eLocal recurrence after radical mastectomy for breast cancer refers to the recurrence of the ipsilateral chest wall or (and) local lymph nodes after surgery. The recurrence rate is about 5%-30%, of which chest wall recurrence is the most common, accounting for 50%-94%. Local recurrence is a sign of other distant metastases in breast cancer and is an important factor affecting survival after breast cancer surgery[2,7]. Chest wall metastasis can occur at any time after breast cancer surgery. Among the 99 patients with isolated chest wall recurrence collected in this study, the DFS was 1-264 months, the median DFS was 36 months, and the 3-year disease-free survival rate was 44.6%, 5 years was 24.2%. According to literature reports, local recurrence is the mainstay within 2\u0026ndash;3 years. After recurrence, 60%-80% of patients develop distant metastases, including lung, liver, and bone metastases[9]. It is of great significance to analyze the risk factors of local recurrence in breast cancer patients and take corresponding preventive measures to improve the prognosis of breast cancer patients. This article is the most comprehensive study to collect data on isolated chest wall recurrence after breast cancer surgery and secondary biopsy after recurrence.\u003c/p\u003e \u003cp\u003eRelevant studies have shown that the recurrence and metastasis of breast cancer after surgery are related to a variety of factors. Age, tumor size, lymph node metastasis, pathological type, hormone receptor status and her-2 expression status, postoperative staging, and postoperative treatment methods may be related to the recurrence and metastasis of breast cancer after surgery[10,11]. The histological grade is closely related to tumor invasion and metastasis, and is also positively related to visceral metastasis, the higher the grade, the higher the degree of malignancy, and the earlier the local invasion and distant metastasis. Primary tumor size and local lymph node metastasis are the two main factors affecting tumor TNM staging. Most studies have shown that the larger the tumor, the more lymph node metastasis, the higher the risk of local recurrence and distant metastasis, and the worse the prognosis. The size of the tumor indirectly reflects its biological characteristics, and lymph node metastasis is one of the most common ways of tumor metastasis. Therefore, the size of the tumor and the number of lymph node metastasis are closely related to the postoperative local recurrence of breast cancer[12,13]. The results of the univariate analysis in this study found that age, postoperative T stage, and postoperative N stage were associated with DFS, but multivariate analysis results showed that they were not independent risk factors for DFS, but tissue grade was an independent risk factor for DFS.\u003c/p\u003e \u003cp\u003eMore and more researchers are devoted to the molecular biology research of breast cancer recurrence and metastasis, hoping to clarify the molecular mechanism of breast cancer recurrence and metastasis from the perspective of molecular biology, so as to develop drugs that can effectively inhibit breast cancer recurrence and metastasis. At present, the molecular biological markers associated with breast cancer recurrence mainly include ER, PR, Ki-67, Her-2, and so on. Studies have found that patients with hormone receptor-positive cells have a high degree of cell differentiation and a low degree of malignancy [14\u0026ndash;16]. ER and PR positivity are one of important protective factors for the recurrence and prognosis of breast cancer patients, and the risk of recurrence and metastasis of breast cancer patients receiving endocrine therapy is significantly reduced [15]. Ki-67 is an important regulator of the cell cycle and cell proliferation. Protein antigen, the higher the Ki-67, the faster the cell proliferation, the higher the degree of malignancy, and the worse the prognosis [16]. Studies have found that the expression product of the oncogene Her-2 is a key factor regulating tumor growth and plays an important role in the occurrence, development, metastasis, and prognosis of breast cancer [15]. Faneyte et al. found that the 5-year survival rate of patients with overexpression of her-2 was significantly lower than that of patients with negative expression of her-2[17]. In addition, patients with overexpression of her-2 were not sensitive to conventional adjuvant therapy and were more likely to develop local lymph node metastasis, which would develop a poor prognosis. The results of multivariate analysis in this study showed that positive hormone receptor expression, ki-67\u0026thinsp;\u0026ge;\u0026thinsp;14, and her-2 positive were independent risk factors for chest wall recurrence.\u003c/p\u003e \u003cp\u003eIn recent years, breast cancer tends to be younger. Young patients have stronger tumor invasiveness, faster disease progression, and earlier local recurrence and distant metastasis. Some studies believe that younger age is an independent risk factor for breast cancer recurrence and metastasis after surgery. Reports on the relationship between local recurrence of cancer are inconsistent[18\u0026ndash;21]. This study divided age into \u0026ge;\u0026thinsp;50-year-old group and \u0026lt;\u0026thinsp;50-year-old group. Univariate analysis showed that the DFS of different age groups was statistically different, but multivariate analysis showed that age was not an independent risk factor for chest wall recurrence.\u003c/p\u003e \u003cp\u003eThe main methods of breast cancer treatment include surgery, chemotherapy, radiotherapy, targeted therapy, endocrine therapy, etc. Studies have found that reasonable and effective adjuvant therapy after radical mastectomy can significantly improve the 5-year survival rate of patients. In terms of postoperative adjuvant chemotherapy, adjuvant chemotherapy after breast cancer surgery can significantly prolong the DFS of local recurrence, especially for hormone receptor-negative patient[22,23]. Another study confirmed that postoperative adjuvant endocrine therapy can significantly reduce the rate of local recurrence and distant metastasis[24]. Regarding the sequence of postoperative adjuvant chemotherapy and endocrine therapy, it is recommended to complete adjuvant chemotherapy before starting endocrine therapy[22,23]. In terms of local radiotherapy, many studies have confirmed that it has a significant effect on controlling the local recurrence rate after breast cancer surgery and improving long-term survival[24,25], and it is one of the main methods for postoperative local treatment of breast cancer, especially for patients with \u0026ge;\u0026thinsp;4 positive axillary lymph nodes[9,26,27]. The univariate analysis results of this study showed that the comprehensive treatment mode of postoperative adjuvant chemotherapy, endocrine therapy, and radiotherapy can significantly prolong the DFS of chest wall metastasis after breast cancer surgery. Further COX multivariate analysis showed that adjuvant chemotherapy was an independent protective factor for chest wall metastasis after breast cancer surgery. Targeted therapy was not included in this study's univariate and multivariate analysis because there were only 9 patients who received targeted therapy in the collected patients, and the number of cases was unbalanced with an obvious bias.\u003c/p\u003e \u003cp\u003eThis study had several limitations. Firstly, the clinical and molecular factors were assessed retrospectively from medical records, which may have introduced errors or missing data. Additionally, the study did not perform a rigorous assessment of inter-rater reliability to ensure consistency in data collection and interpretation. Lastly, the study only analyzed DFS as the primary outcome, and did not assess other clinically relevant outcomes, such as overall survival or quality of life. Therefore, the study may not provide a comprehensive understanding of the impact of chest wall metastasis on breast cancer patients. while this study provides valuable insights into the clinical and molecular factors associated with chest wall metastasis in breast cancer patients, the results should be interpreted with caution due to the limitations discussed above. Further studies with larger sample sizes, more diverse patient populations, and longer follow-up periods are needed to validate these findings and provide a more comprehensive understanding of the impact of chest wall metastasis on breast cancer patients.\u003c/p\u003e \u003cp\u003eIn conclusion, this study showed that surgical grade, postoperative ER, PR, Ki-67, HER-2 expression, and postoperative adjuvant chemotherapy were independent risk factors affecting the local recurrence of breast cancer after surgery. As local recurrence after breast cancer surgery increases the risk of distant metastasis, therefore, identifying the risk factors of recurrence and selecting individualized comprehensive treatment for patients is crucial to reduce the risk of postoperative local recurrence, improve prognosis, and enhance survival.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics statement\u003c/h2\u003e \u003cp\u003e Approval of the research protocol by an institutional reviewer board: The study protocol was approved by the Ethics Committee of PLA General Hospital.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eInformed consent:\u003c/h2\u003e \u003cp\u003eInformed consent was obtained from the patients for use of their data for experimentation.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eConflicts of interest:\u003c/h2\u003e \u003cp\u003eAll authors declare no conflict of interest.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study received no specific funding from public, commercial, or not-for-profit funding entities\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eYanrong Wang: Data curation, Formal analysis, Investigation, Validation, Writing \u0026ndash; original draft, Writing \u0026ndash; review \u0026amp; editing. Ming Gao: Investigation, Validation, Data curation. Yan Huan: Investigation, Validation. Junhao You: Investigation, Validation. Lijuan Ding: Investigation, Validation,. Guanghai Dai: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Supervision, Writing \u0026ndash; review \u0026amp; editing. Xia Zhang: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Writing \u0026ndash; review \u0026amp; editing.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eGD contributed to study design and conception; XZ was responsible for the conduct and supervision of the study; YW, HY and MG were involved in data collection; YW and HY contributed to the statistical analysis; JY and LD made telephone follow-up; YW drafted the manuscript and polished the language. All authors have read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData availability statement\u003c/h2\u003e \u003cp\u003eThe relevant data supporting the conclusions of this article will be available by contacting the corresponding authors upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBuchanan, C.L.; Dorn, P.L.; Fey, J.; Giron, G.; Naik, A.; Mendez, J.; Murphy, C.; Sclafani, L.M. Locoregional recurrence after mastectomy: incidence and outcomes. \u003cem\u003eJournal of the American College of Surgeons\u003c/em\u003e \u003cstrong\u003e2006\u003c/strong\u003e, \u003cem\u003e203\u003c/em\u003e, 469\u0026ndash;474.\u003c/li\u003e\n\u003cli\u003eHalverson, K.J.; Perez, C.A.; Kuske, R.R.; Garcia, D.M.; Simpson, J.R.; Fineberg, B. 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Benefits, risks, and safety of external beam radiation therapy for breast cancer. \u003cem\u003eInternational Journal of Women's Health\u003c/em\u003e \u003cstrong\u003e2015\u003c/strong\u003e, \u003cem\u003e7\u003c/em\u003e, 449\u0026ndash;458, doi:10.2147/IJWH.S55552.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"breast neoplasms, isolated chest wall recurrence, treatment, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-4577325/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4577325/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eTo investigate the clinical features, molecular subtypes, and factors influencing metastasis in patients with breast cancer chest wall metastasis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe collected the clinical data of patients who developed isolated chest wall metastasis following radical surgery for breast cancer. The molecular subtypes of the primary lesions and secondary biopsy lesions in patients with chest wall metastasis were analyzed and summarized. The disease-free survival (DFS) after breast cancer surgery and its influencing factors were also documented.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOf the 99 cases of isolated chest wall recurrence included in our study, DFS varied from 1 to 264 months, with a median DFS of 36 months. The 3-year disease-free survival rate was 44.6%, while the 5-year rate was 24.2%. Molecular subtype changes occurred in a total of 28 cases before and after metastasis, accounting for 34% of the cases. COX multivariate analysis revealed that pathological type, surgical staging, postoperative expression status of ER (estrogen receptor), PR (progesterone receptor), Ki-67, HER-2 (human epidermal growth factor receptor-2), and the receipt of adjuvant chemotherapy after surgery were independent factors affecting chest wall recurrence and metastasis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eLocal recurrence after breast cancer surgery increases the risk of distant metastasis. Identifying high-risk factors for recurrence enables the tailoring of individualized comprehensive treatment plans based on the patient's condition, thus reducing the risk of local recurrence and improving survival outcomes.\u003c/p\u003e","manuscriptTitle":"Analysis of prognostic and predictive factors of isolated chest wall recurrence in breast cancer after mastectomy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-16 17:21:39","doi":"10.21203/rs.3.rs-4577325/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":"ecb53f86-658e-4fd1-a9fb-35ca5f60b530","owner":[],"postedDate":"July 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-09-03T11:02:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-16 17:21:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4577325","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4577325","identity":"rs-4577325","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}