{"paper_id":"3da54fd2-b321-4a0f-95eb-49a94c74b810","body_text":"Comparison of local recurrence outcomes between breast conservation therapy versus mastectomy for treatment of breast cancer among young woman: A systematic review and meta-analysis | 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 Systematic Review Comparison of local recurrence outcomes between breast conservation therapy versus mastectomy for treatment of breast cancer among young woman: A systematic review and meta-analysis Xiaowen Ma, Yiming Sun, Qi Guo, Feng Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4846744/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Recent clinical trials comparing local recurrence rates in young breast cancer(BC) patients after breast-conserving therapy (BCT) vs. mastectomy are scarce. This meta-analysis aims to determine the optimal surgical approach for this group by assessing local recurrence (LR) rates between BCT and mastectomy. Methods: We systematically searched four electronic databases (Medline, PubMed, Cochrane Library, and Web of Science) for relevant studies comparing LR rates in BC patients ≤40 years old treated with BCT plus radiotherapy or mastectomy. Studies meeting the inclusion criteria were synthesized using a random-effects model, with a focus on LR rates. We conducted sensitivity analyses and meta-regression to assess publication bias and heterogeneity, ensuring a rigorous evaluation of the available evidence. Results : Out of 485 screened citations, 11 studies encompassing 9215 patients were included, with 4190 undergoing BCT and 5025 undergoing mastectomy. The summary OR revealed a significantly higher risk of LR for BCT compared to mastectomy among young breast cancer patients (OR = 1.63; 95% CI: 1.25-2.13). Specifically, the BCT group exhibited a higher 5-year LR rate (OR = 1.86, 95% CI: 1.13-2.62) and a 5-10-year LR rate (OR = 1.50, 95% CI: 1.00-2.25) compared to the mastectomy group. This trend held true across tumor stages, with the BCT group showing increased LR risk for both T1-2 (OR = 1.88, 95% CI: 1.20-2.94) and T1-4 (OR = 1.46, 95% CI: 1.02-2.10) stages. Similarly, nodal status analysis indicated a higher LR risk for BCT in N0-1 (OR = 2.56, 95% CI: 1.90-3.44) and N0-3 (OR = 1.38, 95% CI: 0.99-1.93) stages. Notably, among very young women (age ≤ 35), the difference in LR rate between BCT and mastectomy was pronounced (OR = 2.04, 95% CI: 1.48-2.81). Overall, for breast cancer patients aged ≤ 40 years, the BCT group consistently demonstrated a higher risk of LR compared to the mastectomy group (OR = 1.53, 95% CI: 1.10-2.13). Conclusion : Our meta-analysis revealed that among young breast cancer patients, BCT was associated with a significantly elevated risk of LR compared to mastectomy, particularly in those ≤35 years old. This heightened risk persisted across various tumor and nodal stages. For very young breast cancer patients, a comprehensive consideration of surgical options is warranted, with caution exercised in selecting BCT. While overall survival (OS) rates were comparable between the two groups in young women, further research is warranted to elucidate these findings and guide clinical decision-making. [1-3] breast cancer local recurrence rate young woman breast-conserving therapy mastectomy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Literature shows comparable long-term survival rates between women undergoing BCT + WBRT and radical mastectomy [ 1 – 3 ] , with some newer data suggesting superior BC-specific survival and OS with BCT [ 4 – 10 ] . Despite advantages in OS and cause-specific survival over mastectomy without radiation [ 11 – 16 ] , young BC patients often face more aggressive disease and poorer prognosis [ 17 – 21 ] , especially those ≤ 35 years, with reported 10-year LR rates exceeding 30% [ 22 – 23 ] . Young age independently elevates LR risk post-BCT + WBRT [ 17 , 24 – 26 ] . Thus, we conducted a meta-analysis to assess BCT's efficacy vs mastectomy in reducing LR rates among young BC patients (≤ 40 years, with ≤ 35 years considered very young), as per ESBCS guidelines [ 27 – 28 ] . Methods Literature search The primary objective of this systematic review and meta-analysis was to comprehensively evaluate and report on the local recurrence outcomes observed in under-40 patients who underwent BCT or mastectomy for breast cancer. A thorough literature search by three reviewers, Xiaowen M, Yiming S, and Qi G, encompassed Medline, PubMed, Cochrane, and Web of Science from January 1, 2002 to January 1, 2022, without language or date restrictions. MeSH terms \"Breast Neoplasms,\" \"surgery,\" \"therapy,\" \"recurrence,\" and \"young\" were used. Clinical trials and RCTs were prioritized. Relevant studies comparing BCT vs. mastectomy with reported HR/RR/OR underwent independent screening, full-text review, and manual reference checks. EUSOMA and NCCN 2022 guidelines were reviewed. Only comparative studies meeting criteria were included in the meta-analysis, excluding ecological studies, case reports, reviews, and editorials. Eligibility criteria To be included in the meta-analysis, studies had to fulfill the following stringent criteria: (1) They must present adjusted risk estimates that directly compare BCT to mastectomy in under-40 patients diagnosed with BC, excluding those with prior cancer history or metastatic disease. (2) The studies had to be independent, without duplicating results published elsewhere; in cases of overlapping data, the larger sample size study was prioritized. (3) Clear reporting of LR rates or the number of recurrence cases was mandatory, and studies lacking a comparative group were excluded from consideration. Data extraction Data extraction was meticulously performed by three authors (Xiaowen M, Yiming S, and Qi G) in an independent yet collaborative manner, ensuring unanimity in outcomes. In cases where outcome data was incomplete, the corresponding authors were promptly contacted to solicit specific information or clarify details. A standardized protocol guided the data-collection process, facilitating the systematic extraction of pertinent information from each eligible study. For each study, we recorded an array of details, including the first author's name, publication year, study specifics (aims, patient accrual period, country of origin [single-center or population-based registry], eligibility criteria, median follow-up, T and N staging, median age, local recurrence (LR) and regional recurrence (RR) rates, hazard ratios/risk ratios, and p-values). Additionally, we documented the patient count and treatment specifics for both arms (BCT and mastectomy), encompassing the number of patients receiving adjuvant/neoadjuvant chemotherapy, adjuvant endocrine therapy, targeted therapy, and radiotherapy. Data analysis and statistical methods The HR values were derived directly from the authors' original datasets when not explicitly reported in the publications. Statistical analyses were executed utilizing RevMan version 5.3, with OR estimated for dichotomous outcomes employing a robust random-effects model. For continuous outcomes, a random-effects model with 95% confidence intervals (CI) was applied. Statistical significance was established at P < 0.05 or when the 95% CI excluded 1.00. Cochran's Q test and the I² statistic were leveraged to assess heterogeneity across studies, with I² values exceeding 50% indicative of significant heterogeneity and 0% suggesting no heterogeneity. To visually inspect publication bias, funnel plots were constructed, and their validity was reinforced through the Egger test, renowned for its enhanced statistical power. In the absence of heterogeneity, a fixed-effect model was adopted for the respective outcome measures. A sensitivity analysis in Stata version 17 delved into potential sources of heterogeneity and evaluated the robustness of results when estimating OR for dichotomous variables. Furthermore, regression analysis was conducted to discern the influence of tumor size and lymph node status on study outcomes across different investigations, thereby pinpointing potential sources of heterogeneity. Result Results of search strategy After a meticulous search utilizing the specified MeSH terms and additional sources, a total of 485 articles were initially identified. Following a rigorous screening process, 215 abstracts were selected for further examination based on their relevance. Upon thorough review of the full texts of these 215 studies, 204 were excluded primarily due to the absence of a direct comparison between BCT and mastectomy in terms of LR rates or the lack of pertinent HR/OR/RR data comparing these two treatment modalities. Consequently, a comprehensive flowchart (Fig. 1) was constructed to illustrate the article selection process and ensure transparency in the methodology. Description of studies The characteristics of the studies encompassed in this meta-analysis are succinctly presented in Table 1, detailing the total case count, publication year and country, study design, age and tumor stage controls, and follow-up duration for each study. The distribution of T stage and N stage among patients in the BCT and mastectomy groups is outlined in Table 2, revealing a higher prevalence of tumors >2 cm in the mastectomy group across five studies [32,34,35,37,38] and a greater percentage of positive axillary lymph nodes in the mastectomy group across four studies [32,33,35,36] . The meta-analysis revealed a significant difference in tumor size between BCT and mastectomy groups among under-40 patients, with BCT patients having a higher proportion of small tumors (≤T1) (OR=1.38, 95%CI: 1.23-1.56, P<0.00001). And forest plot illustrates that the BCT group has a higher proportion of patients without positive lymph node (N0) compared to the mastectomy group among patients under 40 years old (OR=1.32, 95%CI: 1.12-1.54, P=0.0007). Table 3 records the administration of adjuvant and neoadjuvant chemotherapy, adjuvant endocrine therapy, adjuvant targeted therapy, and adjuvant radiotherapy in both treatment groups. Notably, all patients undergoing BCT in five out of six studies [32-37] received adjuvant radiotherapy, while only 10% to 69% of mastectomy patients did, resulting in an overall radiotherapy ratio of 54.5% for the mastectomy group. The BCT group exhibited a significantly higher rate of radiotherapy compared to the mastectomy group (OR=2.28; 95% CI: 1.69-3.07; P<0.00001). However, for those studies with detailed data, the ORs for patients receiving adjuvant chemotherapy and hormonotherapy following mastectomy and BCT were not statistically significant (chemotherapy OR=0.92; 95% CI: 0.81-1.05; P=0.12; hormonotherapy OR=1.06; 95% CI: 0.88-1.28; P=0.51). Due to insufficient data, an analysis of neoadjuvant chemotherapy and adjuvant targeted therapy was not feasible. Table 4 summarizes the number of patients experiencing local recurrence (LR) in both groups, accompanied by the corresponding LR rates, HR/OR values, and P values. This compilation encompasses 11 population-based studies, totaling 9215 patients under 40 years old, with 4190 undergoing BCT and 5025 undergoing mastectomy. Four of these studies [31,32,33,37] reported statistically significant results, suggesting a potentially higher LR rate in the BCT group compared to the mastectomy group. Lastly, Table 5 evaluates the methodological quality of the observational studies using the Newcastle-Ottawa scale, providing an assessment of their rigor and credibility. All 11 articles received a Newcastle-Ottawa Scale (NOS) score ranging from 7 to 9, indicating medium to high quality. Meta-analysis results: 1 Subgroup analysis by follow up duration in young breast cancer patients (age≤40) comparing BCT and mastectomy. In our comprehensive meta-analysis, we analyzed 11 studies contributing 15 risk estimates, with four studies presenting two estimates based on median follow-up durations. Notably, the BCT group exhibited a 63% higher LR rate compared to the mastectomy group. Our analysis revealed a significant association between BCT and an elevated risk of LR (OR=1.63; 95% CI: 1.25-2.13), as depicted in Figure 2. Heterogeneity was observed among the included studies, with I²=70.2% and chi-square P=0.000. Subgroup analysis further elaborated that significant differences in LR rates existed between follow-up groups, specifically at 5 years (OR=1.86; 95% CI: 1.31-2.62) and 5_11 years (OR=1.50; 95% CI: 1.00-2.25). Remarkably, the 5-year LR rate in the BCT group was 86% higher than that in the mastectomy group. Sensitivity analysis confirmed the stability of our findings, with consistent results across different studies, as evidenced in Figure 3. The Egger's test (P=0.087) indicated no substantial publication bias. Regression analysis revealed that T stage (coefficient=-0.244, P=0.530), N stage (coefficient=-0.120, P=0.547), and follow-up time (coefficient=-0.306, P=0.333) did not significantly influence the OR. Means the differences in T stage, N stage, and follow-up among the included studies do not have a significant impact on the OR values of LR. However, the extremely low P-value obtained from the test of residual homogeneity hinted at a need for further model refinement or analysis to better elucidate the variations in LR rates, as illustrated in Figure 4. 2 Subgroup analysis by tumor stage duration in young breast cancer patients (age≤40) comparing BCT and mastectomy. As shown in Figure 5, both T1-2 patients [OR=1.88, 95% CI: 1.20-2.94] and T1-4 patients [OR=1.46, 95% CI: 1.02-2.10] in the BCT group demonstrated a significantly elevated risk of LR compared to those in the mastectomy group. The heterogeneity tests for these subgroups revealed substantial heterogeneity, with I²=70.2%, P=0.005 for T1-2 patients and I²=73.5%, P=0.000 for T1-4 patients, indicating variations among the included studies. Nonetheless, the sensitivity analysis underscored the robustness and reliability of our findings, reinforcing the significance of the observed differences in LR risk between the BCT and mastectomy groups across various T stages. 3 Subgroup analysis by node stage duration in young breast cancer patients (age≤40) comparing BCT and mastectomy. The meta-analysis unveiled a noteworthy disparity in LR risk among N0-1 patients, with those undergoing BCT experiencing a significantly elevated risk compared to mastectomy patients (OR=2.56,95% CI: 1.90-3.44), as depicted in Figure 6. However, this trend was not replicated in the N0-3 patient subgroup, where the BCT group did not exhibit a significantly higher risk of LR compared to the mastectomy group(OR=1.38,95% CI: 0.99-1.93). The heterogeneity test for the N0-1 patient subset returned an I²=0.0%, P-value=0.542, indicating an absence of significant heterogeneity among the contributing studies. But the sensitivity analysis underscored the robustness and reliability of our findings, reinforcing the distinct patterns of LR risk observed across different lymph node status categories. 4 Subgroup analysis by age group duration in breast cancer patients comparing BCT and mastectomy. As depicted in Figure 7, both age subgroups within the BCT group exhibited a significantly elevated risk of LR compared to the mastectomy group. Specifically, for patients aged ≤35 years(OR=2.04,95% CI: 1.48-2.81), for those aged ≤40 years(OR=1.53,95% CI: 1.10-2.13). The heterogeneity test for the first age subgroup (≤35 years) , I²= 27.9% P=0.239, indicating no significant heterogeneity among the included studies. In contrast, the heterogeneity test for the second age subgroup (≤40 years) showed I²=73.4%,P-value= 0.000, suggesting substantial heterogeneity. However, despite this heterogeneity in the second subgroup, the sensitivity analysis, confirmed the robustness and reliability of our findings, reinforcing the significantly higher risk of LR associated with BCT compared to mastectomy in both age subgroups. Discussion In the past, mastectomy has been the commonly accepted method for treating BC. However, several randomized clinical trials have shown that BCT can achieve similar OS rates in patients with EBC [ 4 – 10 ] . Nevertheless, there is ongoing debate regarding the use of BCT in patients under the age of 40, as young age has been identified as an independent risk factor for LR after conservative treatment. Additionally, more aggressive tumors are often found in this age group. [ 17 , 18 ] Our comprehensive meta-analysis, synthesizing data from 11 robust studies, has provided valuable insights into the comparative efficacy of BCT and mastectomy in managing I-IV stage breast cancer. The primary outcome of interest, LR, was significantly higher in the BCT group, with a 63% increased risk compared to the mastectomy group, as indicated by an OR of 1.63 (95% CI: 1.25–2.13), despite the higher utilization of radiotherapy, smaller tumor size, and absence of lymph node involvement (N 0 ) in the BCT group. In keeping with Fisher S et al. investigated survival in stage I-III breast cancer patients by surgical treatment and found that while LR rates were higher with BCT, the impact on overall survival was minimal in a publicly funded health care system [ 8 ] . To mitigate potential selection bias related to tumor stage, subgroup analysis was conducted. In the subgroup analysis, subgroup analyses further stratified by follow-up periods revealed a pronounced increase in the 5-year LR rate, with an 86% higher risk in the BCT group. This trend, though slightly reduced, persisted at the 10-year mark, suggesting a lasting impact of treatment choice on recurrence risk. The conclusion of this paper is similar to Lagendijk M et al. conducted a large-scale study involving 129,692 patients and found that BCT was associated with a higher risk of LR, particularly within the first 5 years post-surgery [ 4 ] . The significantly higher LR rates in young women (age ≤ 40), particularly in those with T1-2 and N0-1 stages, underscore the importance of considering patient age and tumor characteristics when deciding on the surgical approach. The robustness of our findings is supported by sensitivity analyses. In keeping with Agarwal S et al. reported that the effect of BCT vs. mastectomy on disease-specific survival for early-stage breast cancer showed a higher LR rate in the BCT group, emphasizing the need for careful patient selection and follow-up [ 5 ] . Both two age group of the BCT group showed a significantly higher risk of LR rate[OR = 2.04,95%CI:1.48–2.81, ≤ 35years old; OR = 1.53, 95%CI:1.10–2.13, ≤ 40years old] compared with mastectomy group. In particular, for breast cancer patients aged 35 years, LR was higher in the BCT group, 104% higher than in the mastectomy group. The conclusion from our meta-analysis is that BCT, despite its benefits in terms of breast preservation and cosmesis, may be associated with a higher risk of local recurrence, particularly in specific patient subgroups. This information is crucial for clinicians and patients when weighing the options of surgical treatments for early-stage breast cancer. Future research should continue to explore the reasons behind the increased recurrence rates in BCT and identify methods to mitigate this risk while preserving the benefits of breast conservation. And Local failures as a first event are strongly associated with BCT. [ 40 ] The findings of this meta-analysis suggest that mastectomy may be a more suitable option for EBC patients compared to BCT, same to EBC patients. About limitations, the current meta-analysis, while providing valuable insights into the differences in LR rates between BCT and mastectomy, has several limitations that should be acknowledged. Heterogeneity: Despite the robust statistical methods employed, significant heterogeneity among the studies was observed, indicating variability in patient populations, treatment protocols, and outcomes measures. Publication Bias: Although Egger's test did not suggest significant publication bias, the possibility of unpublished studies influencing the results cannot be entirely ruled out. Confounding Factors: The meta-regression analysis did not identify statistically significant relationships between T_stage, N_stage, follow_up, and LR rates, which may indicate the presence of unmeasured confounding factors. Generalizability: The patient populations in the included studies may not be fully representative of all breast cancer patients, potentially limiting the generalizability of the findings. Data Sources: The reliance on published data may have introduced reporting biases, and detailed individual patient data could provide a more nuanced understanding of the LR rates. Treatment Variations: Variations in surgical techniques, radiotherapy protocols, and systemic therapies across studies could affect the comparability of BCT and mastectomy outcomes. Future Perspectives: Looking ahead, there are several areas that warrant further investigation to build upon the findings of this meta-analysis: Individual Patient Data (IPD) Meta-Analysis: An IPD meta-analysis could provide a more detailed and nuanced understanding of the factors influencing LR rates. Subgroup Analyses: Further exploration of subgroups, such as molecular subtypes of breast cancer or specific patient demographics, could reveal additional insights into the differential effects of BCT and mastectomy. The current study is to analyze all breast cancer patients, and further studies can be conducted on age groups. Randomized controlled trials can determine whether patients younger than 35 years old have a higher recurrence rate and whether there is a significant difference in OS. Large, multi-center trials with standardized protocols could provide more robust evidence for comparing BCT and mastectomy outcomes. Quality of Life Assessments: Future research should include quality of life assessments alongside LR rates to offer a comprehensive view of treatment impacts. Declarations Author Contribution Ma Xiaowen ，Sun Yiming and Guo Qi were responsible for literature search and data organization. Ma Xiaowen conducted the data analysis, while Sun Yiming and Ma Xiaowen jointly authored the manuscript. Guo Qi was in charge of reviewing the data analysis results. Zhang Feng was responsible for the final article review. 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Eur J Cancer. 2012 Dec;48(18):3355-77. doi: 10.1016/j.ejca.2012.10.004. Epub 2012 Oct 29. PMID: 23116682. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 Dec 17;366(9503):2087-106. doi: 10.1016/S0140-6736(05)67887-7. PMID: 16360786. Li Y, Lu S, Zhang Y, Wang S, Liu H. Loco-regional recurrence trend and prognosis in young women with breast cancer according to molecular subtypes: analysis of 1099 cases. World J Surg Oncol. 2021 Apr 13;19(1):113. doi: 10.1186/s12957-021-02214-5. PMID: 33849563; PMCID: PMC8042870. Arriagada R, Lê MG, Contesso G, Guinebretière JM, Rochard F, Spielmann M. Predictive factors for local recurrence in 2006 patients with surgically resected small breast cancer. Ann Oncol. 2002 Sep;13(9):1404-13. doi: 10.1093/annonc/mdf227. PMID: 12196366. Erić I, Petek Erić A, Koprivčić I, Babić M, Pačarić S, Trogrlić B. Independent factors FOR poor prognosis in young patients with stage I-III breast cancer. Acta Clin Croat. 2020 Jun;59(2):242-251. doi: 10.20471/acc.2020.59.02.07. PMID: 33456111; PMCID: PMC7808215. Quan ML, Paszat LF, Fernandes KA, Sutradhar R, McCready DR, Rakovitch E, Warner E, Wright FC, Hodgson N, Brackstone M, Baxter NN. The effect of surgery type on survival and recurrence in very young women with breast cancer. J Surg Oncol. 2017 Feb;115(2):122-130. doi: 10.1002/jso.24489. Epub 2017 Jan 5. PMID: 28054348. Maishman T, Cutress RI, Hernandez A, Gerty S, Copson ER, Durcan L, Eccles DM. Local Recurrence and Breast Oncological Surgery in Young Women With Breast Cancer: The POSH Observational Cohort Study. Ann Surg. 2017 Jul;266(1):165-172. doi: 10.1097/SLA.0000000000001930. PMID: 27455160; PMCID: PMC5639998. I Frandsen J, Ly D, Cannon G, Suneja G, Matsen C, Gaffney DK, Wright M, Kokeny KE, Poppe MM. In the Modern Treatment Era, Is Breast Conservation Equivalent to Mastectomy in Women Younger Than 40 Years of Age? A Multi-Institution Study. Int J Radiat Oncol Biol Phys. 2015 Dec 1;93(5):1096-103. doi: 10.1016/j.ijrobp.2015.08.044. Epub 2015 Sep 1. PMID: 26581146. Yau TK, Choi CW, Sze H, Soong IS, Lee AW. Should young age be a contra-indication to breast conservation treatment in Chinese women? Twelve-year experience from a public cancer centre in Hong Kong. Hong Kong Med J. 2009 Apr;15(2):94-9. PMID: 19342734. Coulombe G, Tyldesley S, Speers C, Paltiel C, Aquino-Parsons C, Bernstein V, Truong PT, Keyes M, Olivotto IA. Is mastectomy superior to breast-conserving treatment for young women? Int J Radiat Oncol Biol Phys. 2007 Apr 1;67(5):1282-90. doi: 10.1016/j.ijrobp.2006.11.032. Epub 2007 Feb 1. PMID: 17275207. van der Sangen MJ, van de Wiel FM, Poortmans PM, Tjan-Heijnen VC, Nieuwenhuijzen GA, Roumen RM, Ernst MF, Tutein Nolthenius-Puylaert MC, Voogd AC. Are breast conservation and mastectomy equally effective in the treatment of young women with early breast cancer? Long-term results of a population-based cohort of 1,451 patients aged ≤ 40 years. Breast Cancer Res Treat. 2011 May;127(1):207-15. doi: 10.1007/s10549-010-1110-x. Epub 2010 Aug 12. PMID: 20703938. Plichta JK, Rai U, Tang R, Coopey SB, Buckley JM, Gadd MA, Specht MC, Hughes KS, Taghian AG, Smith BL. Factors Associated with Recurrence Rates and Long-Term Survival in Women Diagnosed with Breast Cancer Ages 40 and Younger. Ann Surg Oncol. 2016 Oct;23(10):3212-20. doi: 10.1245/s10434-016-5404-z. Epub 2016 Jul 12. PMID: 27406095. Wang L, He Y, Li J, Wang T, Xie Y, Fan Z, Ouyang T. Comparisons of breast conserving therapy versus mastectomy in young and old women with early-stage breast cancer: long-term results using propensity score adjustment method. Breast Cancer Res Treat. 2020 Oct;183(3):717-728. doi: 10.1007/s10549-020-05821-0. Epub 2020 Jul 26. PMID: 32715444. Blichert-Toft M, Nielsen M, Düring M, Møller S, Rank F, Overgaard M, Mouridsen HT. Long-term results of breast conserving surgery vs. mastectomy for early stage invasive breast cancer: 20-year follow-up of the Danish randomized DBCG-82TM protocol. Acta Oncol. 2008;47(4):672-81. doi: 10.1080/02841860801971439. PMID: 18465335. Tables Tables 1 to 5 are available in the Supplementary Files section 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-4846744\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Systematic Review\",\"associatedPublications\":[],\"authors\":[{\"id\":337335564,\"identity\":\"e11c8472-1344-4769-ba58-30776eb09d7b\",\"order_by\":0,\"name\":\"Xiaowen Ma\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYDACZuaDDyQMbOrtG85///HBwMaOsBZ2tmQDi4q0BAPGAwaSMwrSkglr4ecxk6g4czjBgPmAgTTPh0OMDYR06DYDbbnZlpZnznYgwdjG4AAzA/vhoxvwaTE7zHzw4cw2m2LLngMHknMM7vAx8KSl3cCvhS3ZWLItjbHhxsGGwzkGz5gZJHjMCGjhMZP+23aYseH+Y8ZmCwMggxgtEhJnDiduOHCMmZmBOC1A70tUpBlLNpxhY+wxSEtmI+iX84fBUSnHz3CGjeHHHxs7fvbDx/BqwQRspCkfBaNgFIyCUYANAABHHVFZ+6jqmQAAAABJRU5ErkJggg==\",\"orcid\":\"\",\"institution\":\"Hangzhou Woman’s Hospital\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Xiaowen\",\"middleName\":\"\",\"lastName\":\"Ma\",\"suffix\":\"\"},{\"id\":337335565,\"identity\":\"6e2ab782-4a2d-47e0-9003-eff5dc8a654b\",\"order_by\":1,\"name\":\"Yiming Sun\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Tongde Hospital Of Zhejiang Province\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yiming\",\"middleName\":\"\",\"lastName\":\"Sun\",\"suffix\":\"\"},{\"id\":337335566,\"identity\":\"6ea845d2-9f7b-4315-9064-e7e6259a70c2\",\"order_by\":2,\"name\":\"Qi Guo\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Hangzhou Woman’s Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Qi\",\"middleName\":\"\",\"lastName\":\"Guo\",\"suffix\":\"\"},{\"id\":337335567,\"identity\":\"765622d7-820c-4e9c-bacb-e0cdb9ed7c42\",\"order_by\":3,\"name\":\"Feng Zhang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Hangzhou Woman’s Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Feng\",\"middleName\":\"\",\"lastName\":\"Zhang\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2024-08-02 08:11:55\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-4846744/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-4846744/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":62119732,\"identity\":\"6bd49a94-e95c-46fd-b2ac-5aba0e47c17c\",\"added_by\":\"auto\",\"created_at\":\"2024-08-09 13:42:41\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":60774,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003earticle selection flowchart\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4846744/v1/eaf519bfdd9ad062c0a5e323.png\"},{\"id\":62118584,\"identity\":\"aa4e0d84-36d9-4098-a364-a41badeb2f1a\",\"added_by\":\"auto\",\"created_at\":\"2024-08-09 13:26:41\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":83265,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThe forest plot of subgroup analysis by follow-up duration in young breast cancer patients comparing BCT and mastectomy.\\u003c/p\\u003e\\n\\u003cp\\u003eNote:1 5year follow up; 2 5-11year follow up\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4846744/v1/8337f1df43f8294968243239.png\"},{\"id\":62118585,\"identity\":\"aeb87081-b1d6-4067-a360-c878b53477bb\",\"added_by\":\"auto\",\"created_at\":\"2024-08-09 13:26:41\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":58179,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eSensitivity test of LR rate in young patients comparing BCT and mastectomy\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4846744/v1/1447fbaeb967230b9a7f3d8c.png\"},{\"id\":62119146,\"identity\":\"a22547aa-c9a8-4ca5-b102-3cada637c117\",\"added_by\":\"auto\",\"created_at\":\"2024-08-09 13:34:41\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":94642,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eRegression analysis of LR rate in young patients comparing BCT and mastectomy\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4846744/v1/23b481210d40a339dfda31e6.png\"},{\"id\":62118586,\"identity\":\"10b98e8d-d49f-436b-a531-24f33e5683c9\",\"added_by\":\"auto\",\"created_at\":\"2024-08-09 13:26:42\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":83459,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThe forest plot of subgroup analysis by tumor stage duration in young breast cancer patients comparing BCT and mastectomy.\\u003c/p\\u003e\\n\\u003cp\\u003eNote: 1:T1-2 \\u0026nbsp;2:T1-4\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"5.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4846744/v1/3a5c402342432e47d897b15a.png\"},{\"id\":62119733,\"identity\":\"88f2fcb9-0312-41b3-8eac-8f2089194570\",\"added_by\":\"auto\",\"created_at\":\"2024-08-09 13:42:45\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":285482,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4846744/v1/31c9df57-7a91-4018-9137-d368799b33e2.pdf\"},{\"id\":62118582,\"identity\":\"8361731a-b357-4633-a21f-a882d3d70fa9\",\"added_by\":\"auto\",\"created_at\":\"2024-08-09 13:26:41\",\"extension\":\"docx\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":57985,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"Tables.docx\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4846744/v1/8bd825a1418712ed2de14203.docx\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Comparison of local recurrence outcomes between breast conservation therapy versus mastectomy for treatment of breast cancer among young woman: A systematic review and meta-analysis\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eLiterature shows comparable long-term survival rates between women undergoing BCT\\u0026thinsp;+\\u0026thinsp;WBRT and radical mastectomy \\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR2\\\" citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]\\u003c/sup\\u003e, with some newer data suggesting superior BC-specific survival and OS with BCT \\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR5 CR6 CR7 CR8 CR9\\\" citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]\\u003c/sup\\u003e. Despite advantages in OS and cause-specific survival over mastectomy without radiation \\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR12 CR13 CR14 CR15\\\" citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]\\u003c/sup\\u003e, young BC patients often face more aggressive disease and poorer prognosis \\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR18 CR19 CR20\\\" citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]\\u003c/sup\\u003e, especially those\\u0026thinsp;\\u0026le;\\u0026thinsp;35 years, with reported 10-year LR rates exceeding 30% \\u003csup\\u003e[\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]\\u003c/sup\\u003e. Young age independently elevates LR risk post-BCT\\u0026thinsp;+\\u0026thinsp;WBRT \\u003csup\\u003e[\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e, \\u003cspan additionalcitationids=\\\"CR25\\\" citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e]\\u003c/sup\\u003e. Thus, we conducted a meta-analysis to assess BCT's efficacy vs mastectomy in reducing LR rates among young BC patients (\\u0026le;\\u0026thinsp;40 years, with \\u0026le;\\u0026thinsp;35 years considered very young), as per ESBCS guidelines \\u003csup\\u003e[\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003eLiterature search\\u003c/p\\u003e \\u003cp\\u003e The primary objective of this systematic review and meta-analysis was to comprehensively evaluate and report on the local recurrence outcomes observed in under-40 patients who underwent BCT or mastectomy for breast cancer. A thorough literature search by three reviewers, Xiaowen M, Yiming S, and Qi G, encompassed Medline, PubMed, Cochrane, and Web of Science from January 1, 2002 to January 1, 2022, without language or date restrictions. MeSH terms \\\"Breast Neoplasms,\\\" \\\"surgery,\\\" \\\"therapy,\\\" \\\"recurrence,\\\" and \\\"young\\\" were used. Clinical trials and RCTs were prioritized. Relevant studies comparing BCT vs. mastectomy with reported HR/RR/OR underwent independent screening, full-text review, and manual reference checks. EUSOMA and NCCN 2022 guidelines were reviewed. Only comparative studies meeting criteria were included in the meta-analysis, excluding ecological studies, case reports, reviews, and editorials.\\u003c/p\\u003e \\u003cp\\u003eEligibility criteria\\u003c/p\\u003e \\u003cp\\u003eTo be included in the meta-analysis, studies had to fulfill the following stringent criteria: (1) They must present adjusted risk estimates that directly compare BCT to mastectomy in under-40 patients diagnosed with BC, excluding those with prior cancer history or metastatic disease. (2) The studies had to be independent, without duplicating results published elsewhere; in cases of overlapping data, the larger sample size study was prioritized. (3) Clear reporting of LR rates or the number of recurrence cases was mandatory, and studies lacking a comparative group were excluded from consideration.\\u003c/p\\u003e \\u003cp\\u003eData extraction\\u003c/p\\u003e \\u003cp\\u003eData extraction was meticulously performed by three authors (Xiaowen M, Yiming S, and Qi G) in an independent yet collaborative manner, ensuring unanimity in outcomes. In cases where outcome data was incomplete, the corresponding authors were promptly contacted to solicit specific information or clarify details. A standardized protocol guided the data-collection process, facilitating the systematic extraction of pertinent information from each eligible study. For each study, we recorded an array of details, including the first author's name, publication year, study specifics (aims, patient accrual period, country of origin [single-center or population-based registry], eligibility criteria, median follow-up, T and N staging, median age, local recurrence (LR) and regional recurrence (RR) rates, hazard ratios/risk ratios, and p-values). Additionally, we documented the patient count and treatment specifics for both arms (BCT and mastectomy), encompassing the number of patients receiving adjuvant/neoadjuvant chemotherapy, adjuvant endocrine therapy, targeted therapy, and radiotherapy.\\u003c/p\\u003e \\u003cp\\u003eData analysis and statistical methods\\u003c/p\\u003e \\u003cp\\u003eThe HR values were derived directly from the authors' original datasets when not explicitly reported in the publications. Statistical analyses were executed utilizing RevMan version 5.3, with OR estimated for dichotomous outcomes employing a robust random-effects model. For continuous outcomes, a random-effects model with 95% confidence intervals (CI) was applied. Statistical significance was established at P\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05 or when the 95% CI excluded 1.00. Cochran's Q test and the I\\u0026sup2; statistic were leveraged to assess heterogeneity across studies, with I\\u0026sup2; values exceeding 50% indicative of significant heterogeneity and 0% suggesting no heterogeneity. To visually inspect publication bias, funnel plots were constructed, and their validity was reinforced through the Egger test, renowned for its enhanced statistical power. In the absence of heterogeneity, a fixed-effect model was adopted for the respective outcome measures.\\u003c/p\\u003e \\u003cp\\u003eA sensitivity analysis in Stata version 17 delved into potential sources of heterogeneity and evaluated the robustness of results when estimating OR for dichotomous variables. Furthermore, regression analysis was conducted to discern the influence of tumor size and lymph node status on study outcomes across different investigations, thereby pinpointing potential sources of heterogeneity.\\u003c/p\\u003e\"},{\"header\":\"Result\",\"content\":\"\\u003cp\\u003eResults of search strategy\\u003c/p\\u003e\\n\\u003cp\\u003eAfter a meticulous search utilizing the specified MeSH terms and additional sources, a total of 485 articles were initially identified. Following a rigorous screening process, 215 abstracts were selected for further examination based on their relevance. Upon thorough review of the full texts of these 215 studies, 204 were excluded primarily due to the absence of a direct comparison between BCT and mastectomy in terms of LR rates or the lack of pertinent HR/OR/RR data comparing these two treatment modalities. Consequently, a comprehensive flowchart (Fig. 1) was constructed to illustrate the article selection process and ensure transparency in the methodology.\\u003c/p\\u003e\\n\\u003cp\\u003eDescription of studies\\u003c/p\\u003e\\n\\u003cp\\u003eThe characteristics of the studies encompassed in this meta-analysis are succinctly presented in Table 1, detailing the total case count, publication year and country, study design, age and tumor stage controls, and follow-up duration for each study.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eThe distribution of T stage and N stage among patients in the BCT and mastectomy groups is outlined in Table 2, revealing a higher prevalence of tumors \\u0026gt;2 cm in the mastectomy group across five studies \\u003csup\\u003e[32,34,35,37,38]\\u0026nbsp;\\u003c/sup\\u003eand a greater percentage of positive axillary lymph nodes in the mastectomy group across four studies\\u003csup\\u003e\\u0026nbsp;[32,33,35,36]\\u003c/sup\\u003e. The meta-analysis revealed a significant difference in tumor size between BCT and mastectomy groups among under-40 patients, with BCT patients having a higher proportion of small tumors (\\u0026le;T1) (OR=1.38, 95%CI: 1.23-1.56, P\\u0026lt;0.00001). And forest plot illustrates that the BCT group has a higher proportion of patients without positive lymph node (N0) compared to the mastectomy group among patients under 40 years old (OR=1.32, 95%CI: 1.12-1.54, P=0.0007).\\u003c/p\\u003e\\n\\u003cp\\u003eTable 3 records the administration of adjuvant and neoadjuvant chemotherapy, adjuvant endocrine therapy, adjuvant targeted therapy, and adjuvant radiotherapy in both treatment groups. Notably, all patients undergoing BCT in five out of six studies\\u003csup\\u003e\\u0026nbsp;[32-37]\\u003c/sup\\u003e received adjuvant radiotherapy, while only 10% to 69% of mastectomy patients did, resulting in an overall radiotherapy ratio of 54.5% for the mastectomy group. The BCT group exhibited a significantly higher rate of radiotherapy compared to the mastectomy group (OR=2.28; 95% CI: 1.69-3.07; P\\u0026lt;0.00001). However, for those studies with detailed data, the ORs for patients receiving adjuvant chemotherapy and hormonotherapy following mastectomy and BCT were not statistically significant (chemotherapy OR=0.92; 95% CI: 0.81-1.05; P=0.12; hormonotherapy OR=1.06; 95% CI: 0.88-1.28; P=0.51). Due to insufficient data, an analysis of neoadjuvant chemotherapy and adjuvant targeted therapy was not feasible.\\u003c/p\\u003e\\n\\u003cp\\u003eTable 4 summarizes the number of patients experiencing local recurrence (LR) in both groups, accompanied by the corresponding LR rates, HR/OR values, and P values. This compilation encompasses 11 population-based studies, totaling 9215 patients under 40 years old, with 4190 undergoing BCT and 5025 undergoing mastectomy. Four of these studies\\u003csup\\u003e\\u0026nbsp;[31,32,33,37]\\u0026nbsp;\\u003c/sup\\u003ereported statistically significant results, suggesting a potentially higher LR rate in the BCT group compared to the mastectomy group.\\u003c/p\\u003e\\n\\u003cp\\u003eLastly, Table 5 evaluates the methodological quality of the observational studies using the Newcastle-Ottawa scale, providing an assessment of their rigor and credibility. All 11 articles received a Newcastle-Ottawa Scale (NOS) score ranging from 7 to 9, indicating medium to high quality.\\u003c/p\\u003e\\n\\u003cp\\u003eMeta-analysis results:\\u003c/p\\u003e\\n\\u003cp\\u003e1\\u0026nbsp;Subgroup analysis by follow up duration in young breast cancer patients (age\\u0026le;40) comparing BCT and mastectomy.\\u003c/p\\u003e\\n\\u003cp\\u003eIn our comprehensive meta-analysis, we analyzed 11 studies contributing 15 risk estimates, with four studies presenting two estimates based on median follow-up durations. Notably, the BCT group exhibited a 63% higher LR rate compared to the mastectomy group. Our analysis revealed a significant association between BCT and an elevated risk of LR (OR=1.63; 95% CI: 1.25-2.13), as depicted in Figure 2. Heterogeneity was observed among the included studies, with I\\u0026sup2;=70.2% and chi-square P=0.000.\\u003c/p\\u003e\\n\\u003cp\\u003eSubgroup analysis further elaborated that significant differences in LR rates existed between follow-up groups, specifically at 5 years (OR=1.86; 95% CI: 1.31-2.62) and 5_11 years (OR=1.50; 95% CI: 1.00-2.25). Remarkably, the 5-year LR rate in the BCT group was 86% higher than that in the mastectomy group.\\u003c/p\\u003e\\n\\u003cp\\u003eSensitivity analysis confirmed the stability of our findings, with consistent results across different studies, as evidenced in Figure 3. The Egger\\u0026apos;s test (P=0.087) indicated no substantial publication bias.\\u003c/p\\u003e\\n\\u003cp\\u003eRegression analysis revealed that T stage (coefficient=-0.244, P=0.530), N stage (coefficient=-0.120, P=0.547), and follow-up time (coefficient=-0.306, P=0.333) did not significantly influence the OR. Means the differences in T stage, N stage, and follow-up among the included studies do not have a significant impact on the OR values of LR. However, the extremely low P-value obtained from the test of residual homogeneity hinted at a need for further model refinement or analysis to better elucidate the variations in LR rates, as illustrated in Figure 4.\\u003c/p\\u003e\\n\\u003cp\\u003e2 Subgroup analysis by tumor stage duration in young breast cancer patients (age\\u0026le;40) comparing BCT and mastectomy.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eAs shown in Figure 5, both T1-2 patients [OR=1.88, 95% CI: 1.20-2.94] and T1-4 patients [OR=1.46, 95% CI: 1.02-2.10] in the BCT group demonstrated a significantly elevated risk of LR compared to those in the mastectomy group. The heterogeneity tests for these subgroups revealed substantial heterogeneity, with I\\u0026sup2;=70.2%, P=0.005 for T1-2 patients and I\\u0026sup2;=73.5%, P=0.000 for T1-4 patients, indicating variations among the included studies. Nonetheless, the sensitivity analysis underscored the robustness and reliability of our findings, reinforcing the significance of the observed differences in LR risk between the BCT and mastectomy groups across various T stages. \\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e3 Subgroup analysis by node stage duration in young breast cancer patients (age\\u0026le;40) comparing BCT and mastectomy.\\u003c/p\\u003e\\n\\u003cp\\u003eThe meta-analysis unveiled a noteworthy disparity in LR risk among N0-1 patients, with those undergoing BCT experiencing a significantly elevated risk compared to mastectomy patients (OR=2.56,95% CI: 1.90-3.44), as depicted in Figure 6. However, this trend was not replicated in the N0-3 patient subgroup, where the BCT group did not exhibit a significantly higher risk of LR compared to the mastectomy group(OR=1.38,95% CI: 0.99-1.93).\\u003c/p\\u003e\\n\\u003cp\\u003eThe heterogeneity test for the N0-1 patient subset returned an I\\u0026sup2;=0.0%, P-value=0.542, indicating an absence of significant heterogeneity among the contributing studies. But the sensitivity analysis underscored the robustness and reliability of our findings, reinforcing the distinct patterns of LR risk observed across different lymph node status categories.\\u003c/p\\u003e\\n\\u003cp\\u003e4 Subgroup analysis by age group duration in breast cancer patients comparing BCT and mastectomy.\\u003c/p\\u003e\\n\\u003cp\\u003eAs depicted in Figure 7, both age subgroups within the BCT group exhibited a significantly elevated risk of LR compared to the mastectomy group. Specifically, for patients aged\\u0026nbsp;\\u0026le;35 years(OR=2.04,95% CI: 1.48-2.81), for those aged\\u0026nbsp;\\u0026le;40 years(OR=1.53,95% CI: 1.10-2.13).\\u003c/p\\u003e\\n\\u003cp\\u003eThe heterogeneity test for the first age subgroup (\\u0026le;35 years) , I\\u0026sup2;= 27.9% P=0.239, indicating no significant heterogeneity among the included studies. In contrast, the heterogeneity test for the second age subgroup (\\u0026le;40 years) showed I\\u0026sup2;=73.4%,P-value= 0.000, suggesting substantial heterogeneity.\\u003c/p\\u003e\\n\\u003cp\\u003eHowever, despite this heterogeneity in the second subgroup, the sensitivity analysis, confirmed the robustness and reliability of our findings, reinforcing the significantly higher risk of LR associated with BCT compared to mastectomy in both age subgroups.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eIn the past, mastectomy has been the commonly accepted method for treating BC. However, several randomized clinical trials have shown that BCT can achieve similar OS rates in patients with EBC \\u003csup\\u003e[\\u003cspan additionalcitationids=\\\"CR5 CR6 CR7 CR8 CR9\\\" citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]\\u003c/sup\\u003e. Nevertheless, there is ongoing debate regarding the use of BCT in patients under the age of 40, as young age has been identified as an independent risk factor for LR after conservative treatment. Additionally, more aggressive tumors are often found in this age group. \\u003csup\\u003e[\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]\\u003c/sup\\u003e\\u003c/p\\u003e \\u003cp\\u003e Our comprehensive meta-analysis, synthesizing data from 11 robust studies, has provided valuable insights into the comparative efficacy of BCT and mastectomy in managing I-IV stage breast cancer. The primary outcome of interest, LR, was significantly higher in the BCT group, with a 63% increased risk compared to the mastectomy group, as indicated by an OR of 1.63 (95% CI: 1.25\\u0026ndash;2.13), despite the higher utilization of radiotherapy, smaller tumor size, and absence of lymph node involvement (N\\u003csub\\u003e0\\u003c/sub\\u003e) in the BCT group. In keeping with Fisher S et al. investigated survival in stage I-III breast cancer patients by surgical treatment and found that while LR rates were higher with BCT, the impact on overall survival was minimal in a publicly funded health care system \\u003csup\\u003e[\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eTo mitigate potential selection bias related to tumor stage, subgroup analysis was conducted. In the subgroup analysis, subgroup analyses further stratified by follow-up periods revealed a pronounced increase in the 5-year LR rate, with an 86% higher risk in the BCT group. This trend, though slightly reduced, persisted at the 10-year mark, suggesting a lasting impact of treatment choice on recurrence risk. The conclusion of this paper is similar to Lagendijk M et al. conducted a large-scale study involving 129,692 patients and found that BCT was associated with a higher risk of LR, particularly within the first 5 years post-surgery \\u003csup\\u003e[\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eThe significantly higher LR rates in young women (age\\u0026thinsp;\\u0026le;\\u0026thinsp;40), particularly in those with T1-2 and N0-1 stages, underscore the importance of considering patient age and tumor characteristics when deciding on the surgical approach. The robustness of our findings is supported by sensitivity analyses. In keeping with Agarwal S et al. reported that the effect of BCT vs. mastectomy on disease-specific survival for early-stage breast cancer showed a higher LR rate in the BCT group, emphasizing the need for careful patient selection and follow-up \\u003csup\\u003e[\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]\\u003c/sup\\u003e.\\u003c/p\\u003e \\u003cp\\u003eBoth two age group of the BCT group showed a significantly higher risk of LR rate[OR\\u0026thinsp;=\\u0026thinsp;2.04,95%CI:1.48\\u0026ndash;2.81, \\u0026le;\\u0026thinsp;35years old; OR\\u0026thinsp;=\\u0026thinsp;1.53, 95%CI:1.10\\u0026ndash;2.13, \\u0026le;\\u0026thinsp;40years old] compared with mastectomy group. In particular, for breast cancer patients aged 35 years, LR was higher in the BCT group, 104% higher than in the mastectomy group.\\u003c/p\\u003e \\u003cp\\u003eThe conclusion from our meta-analysis is that BCT, despite its benefits in terms of breast preservation and cosmesis, may be associated with a higher risk of local recurrence, particularly in specific patient subgroups. This information is crucial for clinicians and patients when weighing the options of surgical treatments for early-stage breast cancer. Future research should continue to explore the reasons behind the increased recurrence rates in BCT and identify methods to mitigate this risk while preserving the benefits of breast conservation. And Local failures as a first event are strongly associated with BCT.\\u003csup\\u003e[\\u003cspan citationid=\\\"CR40\\\" class=\\\"CitationRef\\\"\\u003e40\\u003c/span\\u003e]\\u003c/sup\\u003e The findings of this meta-analysis suggest that mastectomy may be a more suitable option for EBC patients compared to BCT, same to EBC patients.\\u003c/p\\u003e \\u003cp\\u003eAbout limitations, the current meta-analysis, while providing valuable insights into the differences in LR rates between BCT and mastectomy, has several limitations that should be acknowledged. Heterogeneity: Despite the robust statistical methods employed, significant heterogeneity among the studies was observed, indicating variability in patient populations, treatment protocols, and outcomes measures. Publication Bias: Although Egger's test did not suggest significant publication bias, the possibility of unpublished studies influencing the results cannot be entirely ruled out. Confounding Factors: The meta-regression analysis did not identify statistically significant relationships between T_stage, N_stage, follow_up, and LR rates, which may indicate the presence of unmeasured confounding factors. Generalizability: The patient populations in the included studies may not be fully representative of all breast cancer patients, potentially limiting the generalizability of the findings. Data Sources: The reliance on published data may have introduced reporting biases, and detailed individual patient data could provide a more nuanced understanding of the LR rates. Treatment Variations: Variations in surgical techniques, radiotherapy protocols, and systemic therapies across studies could affect the comparability of BCT and mastectomy outcomes.\\u003c/p\\u003e \\u003cp\\u003eFuture Perspectives: Looking ahead, there are several areas that warrant further investigation to build upon the findings of this meta-analysis: Individual Patient Data (IPD) Meta-Analysis: An IPD meta-analysis could provide a more detailed and nuanced understanding of the factors influencing LR rates. Subgroup Analyses: Further exploration of subgroups, such as molecular subtypes of breast cancer or specific patient demographics, could reveal additional insights into the differential effects of BCT and mastectomy. The current study is to analyze all breast cancer patients, and further studies can be conducted on age groups. Randomized controlled trials can determine whether patients younger than 35 years old have a higher recurrence rate and whether there is a significant difference in OS. Large, multi-center trials with standardized protocols could provide more robust evidence for comparing BCT and mastectomy outcomes. Quality of Life Assessments: Future research should include quality of life assessments alongside LR rates to offer a comprehensive view of treatment impacts.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\u003cp\\u003eMa Xiaowen ，Sun Yiming and Guo Qi were responsible for literature search and data organization. Ma Xiaowen conducted the data analysis, while Sun Yiming and Ma Xiaowen jointly authored the manuscript. Guo Qi was in charge of reviewing the data analysis results. Zhang Feng was responsible for the final article review. Each author contributed significantly to the research, with Ma Xiaowen and Sun Yiming playing key roles in both data handling and manuscript preparation, and Guo Qi ensuring the accuracy of the analysis. Zhang Feng's review was instrumental in the manuscript's final quality.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n \\u003cli\\u003eVeronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002 Oct 17;347(16):1227-32. doi: 10.1056/NEJMoa020989. PMID: 12393819.\\u003c/li\\u003e\\n \\u003cli\\u003eVeronesi U, Banfi A, Saccozzi R, Salvadori B, Zucali R, Uslenghi C, Greco M, Luini A, Rilke F, Sultan L. Conservative treatment of breast cancer. A trial in progress at the Cancer Institute of Milan. 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PMID: 28054348.\\u003c/li\\u003e\\n \\u003cli\\u003eMaishman T, Cutress RI, Hernandez A, Gerty S, Copson ER, Durcan L, Eccles DM. Local Recurrence and Breast Oncological Surgery in Young Women With Breast Cancer: The POSH Observational Cohort Study. Ann Surg. 2017 Jul;266(1):165-172. doi: 10.1097/SLA.0000000000001930. PMID: 27455160; PMCID: PMC5639998.\\u003c/li\\u003e\\n \\u003cli\\u003eI Frandsen J, Ly D, Cannon G, Suneja G, Matsen C, Gaffney DK, Wright M, Kokeny KE, Poppe MM. In the Modern Treatment Era, Is Breast Conservation Equivalent to Mastectomy in Women Younger Than 40 Years of Age? A Multi-Institution Study. Int J Radiat Oncol Biol Phys. 2015 Dec 1;93(5):1096-103. doi: 10.1016/j.ijrobp.2015.08.044. Epub 2015 Sep 1. PMID: 26581146.\\u003c/li\\u003e\\n \\u003cli\\u003eYau TK, Choi CW, Sze H, Soong IS, Lee AW. Should young age be a contra-indication to breast conservation treatment in Chinese women? Twelve-year experience from a public cancer centre in Hong Kong. Hong Kong Med J. 2009 Apr;15(2):94-9. PMID: 19342734.\\u003c/li\\u003e\\n \\u003cli\\u003eCoulombe G, Tyldesley S, Speers C, Paltiel C, Aquino-Parsons C, Bernstein V, Truong PT, Keyes M, Olivotto IA. Is mastectomy superior to breast-conserving treatment for young women? Int J Radiat Oncol Biol Phys. 2007 Apr 1;67(5):1282-90. doi: 10.1016/j.ijrobp.2006.11.032. Epub 2007 Feb 1. PMID: 17275207.\\u003c/li\\u003e\\n \\u003cli\\u003evan der Sangen MJ, van de Wiel FM, Poortmans PM, Tjan-Heijnen VC, Nieuwenhuijzen GA, Roumen RM, Ernst MF, Tutein Nolthenius-Puylaert MC, Voogd AC. Are breast conservation and mastectomy equally effective in the treatment of young women with early breast cancer? Long-term results of a population-based cohort of 1,451 patients aged \\u0026le; 40 years. Breast Cancer Res Treat. 2011 May;127(1):207-15. doi: 10.1007/s10549-010-1110-x. Epub 2010 Aug 12. PMID: 20703938.\\u003c/li\\u003e\\n \\u003cli\\u003ePlichta JK, Rai U, Tang R, Coopey SB, Buckley JM, Gadd MA, Specht MC, Hughes KS, Taghian AG, Smith BL. Factors Associated with Recurrence Rates and Long-Term Survival in Women Diagnosed with Breast Cancer Ages 40 and Younger. Ann Surg Oncol. 2016 Oct;23(10):3212-20. doi: 10.1245/s10434-016-5404-z. Epub 2016 Jul 12. PMID: 27406095.\\u003c/li\\u003e\\n \\u003cli\\u003eWang L, He Y, Li J, Wang T, Xie Y, Fan Z, Ouyang T. Comparisons of breast conserving therapy versus mastectomy in young and old women with early-stage breast cancer: long-term results using propensity score adjustment method. Breast Cancer Res Treat. 2020 Oct;183(3):717-728. doi: 10.1007/s10549-020-05821-0. Epub 2020 Jul 26. PMID: 32715444.\\u003c/li\\u003e\\n \\u003cli\\u003eBlichert-Toft M, Nielsen M, D\\u0026uuml;ring M, M\\u0026oslash;ller S, Rank F, Overgaard M, Mouridsen HT. Long-term results of breast conserving surgery vs. mastectomy for early stage invasive breast cancer: 20-year follow-up of the Danish randomized DBCG-82TM protocol. Acta Oncol. 2008;47(4):672-81. doi: 10.1080/02841860801971439. PMID: 18465335.\\u003csup\\u003e\\u003c/sup\\u003e\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003eTables 1 to 5 are available in the Supplementary Files section\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":true,\"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\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"breast cancer, local recurrence rate, young woman, breast-conserving therapy, mastectomy\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4846744/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4846744/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground:\\u003c/strong\\u003e Recent clinical trials comparing local recurrence rates in young breast cancer(BC) patients after breast-conserving therapy (BCT) vs. mastectomy are scarce. This meta-analysis aims to determine the optimal surgical approach for this group by assessing local recurrence (LR) rates between BCT and mastectomy.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethods: \\u003c/strong\\u003eWe systematically searched four electronic databases (Medline, PubMed, Cochrane Library, and Web of Science) for relevant studies comparing LR rates in BC patients ≤40 years old treated with BCT plus radiotherapy or mastectomy. Studies meeting the inclusion criteria were synthesized using a random-effects model, with a focus on LR rates. We conducted sensitivity analyses and meta-regression to assess publication bias and heterogeneity, ensuring a rigorous evaluation of the available evidence.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults\\u003c/strong\\u003e: Out of 485 screened citations, 11 studies encompassing 9215 patients were included, with 4190 undergoing BCT and 5025 undergoing mastectomy. The summary OR revealed a significantly higher risk of LR for BCT compared to mastectomy among young breast cancer patients (OR = 1.63; 95% CI: 1.25-2.13). Specifically, the BCT group exhibited a higher 5-year LR rate (OR = 1.86, 95% CI: 1.13-2.62) and a 5-10-year LR rate (OR = 1.50, 95% CI: 1.00-2.25) compared to the mastectomy group. This trend held true across tumor stages, with the BCT group showing increased LR risk for both T1-2 (OR = 1.88, 95% CI: 1.20-2.94) and T1-4 (OR = 1.46, 95% CI: 1.02-2.10) stages. Similarly, nodal status analysis indicated a higher LR risk for BCT in N0-1 (OR = 2.56, 95% CI: 1.90-3.44) and N0-3 (OR = 1.38, 95% CI: 0.99-1.93) stages. Notably, among very young women (age ≤ 35), the difference in LR rate between BCT and mastectomy was pronounced (OR = 2.04, 95% CI: 1.48-2.81). Overall, for breast cancer patients aged ≤ 40 years, the BCT group consistently demonstrated a higher risk of LR compared to the mastectomy group (OR = 1.53, 95% CI: 1.10-2.13).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion\\u003c/strong\\u003e: Our meta-analysis revealed that among young breast cancer patients, BCT was associated with a significantly elevated risk of LR compared to mastectomy, particularly in those ≤35 years old. This heightened risk persisted across various tumor and nodal stages. For very young breast cancer patients, a comprehensive consideration of surgical options is warranted, with caution exercised in selecting BCT. While overall survival (OS) rates were comparable between the two groups in young women, further research is warranted to elucidate these findings and guide clinical decision-making. \\u003csup\\u003e[1-3]\\u003c/sup\\u003e\\u003c/p\\u003e\",\"manuscriptTitle\":\"Comparison of local recurrence outcomes between breast conservation therapy versus mastectomy for treatment of breast cancer among young woman: A systematic review and meta-analysis\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-08-09 13:26:35\",\"doi\":\"10.21203/rs.3.rs-4846744/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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\":\"7993d88e-20b3-4a27-a792-e6438a3d0b95\",\"owner\":[],\"postedDate\":\"August 9th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2024-08-09T13:26:35+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-08-09 13:26:35\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4846744\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4846744\",\"identity\":\"rs-4846744\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}