De-escalation of oncoplastic surgery and prediction of breast cancer survival beyond serial axillary dissection – A prospective study

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K. Mostaque, M. Kamal, A. M. M. Shariful Alam This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7316406/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: After introduction of the radiotherapy in breast cancer multimodality treatment has disregarded the therapeutic value of axillary lymph node dissection (ALND). Common practice is sentinel lymph node biopsy to count positive nodes only to forecast breast cancer prognosis. Exclusion of symmetry surgery, skin sparing breast reconstruction after oncologic resection of cancer, and addition of ipsilateral ALND might induce spontaneous enlargement of reconstructed smaller breast due to lymphedema effect thus help standardization of technical and safety aspects of Level 2 oncoplastic surgery (OPS). The objectives of study were (1) to observe the outcome after inclusion of ipsilateral ALND in place of symmetry surgery of contralateral normal breast in level 2 OPS and (2) to observe power of assessment of prognosis of pathological node stages and ALND based lymph node ratio (LNR) subgroups. Methods: Study conducted on 51 surgically treated breast cancer patients of a single institution. Data were collected and analyzed of three breast cancer patients treated with oncologic resection of tumor, skin sparing breast reconstruction and ipsilateral ALND avoiding contralateral symmetry surgery, and data of total and positive axillary node counts, patient distribution as per pathological node (pN) stages and LNR subgroups, and DFS and OS at follow-up date when all patients of high-risk LNR died. Results: Six years follow-up of patients who were treated with alternative OPS model indicated spontaneous enlargement of all operated breasts, perfect symmetrisation, and no loco-regional recurrence. The median DFS and overall OS on December 2022 were 49 . 23 and 52 . 63 months respectively. Significant statistical difference was observed of the distribution of patients among pN stages and LNR subgroups ( p = 0 . 000001) and of estimated mean DFS between low- and high-risk ( p = 0 . 000003 ), and intermediate- and high-risk LNR ( p = 0 . 000115 ), and of OS between low- and high-risk ( p = 0 . 000041 ), and intermediate- and high-risk LNR ( p = 0.000161 ) subgroups. Conclusions: Ipsilateral ALND model of OPS is a simpler therapeutic procedure causing spontaneous enlargement of the treated cancer bearing breast leading to almost natural symmetrisation, de-escalate surgical work load and is a safer procedure. ALND is powerful independent forecaster of breast cancer prognosis too. Biological sciences/Cancer Health sciences/Oncology Oncoplastic surgery axillary dissection model Breast cancer predictor axillary node staging Lymph node ratio breast cancer predictor Independent breast cancer survival predictor Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Background Michael Servetus (1509–1533 AD) was the first to introduce ipsilateral axillary lymph node dissection (ALND) with removal of breast tumors and a portion of pectoralis muscles. This surgical method was followed for 300 years and Halsted (1852–1922) made it popular 1 . After introduction of the radiotherapy as multimodality treatment of breast cancer (BC) therapeutic role of ALND was disregarded 1 . Currently occasional ALND is utilized as a therapeutic component of BC surgery and sentinel lymph node biopsy counts only positive axillary nodes for pN staging to forecast prognosis only. Though ALND is a simple procedure physicians focused on disadvantages 2 and surgeons put off thinking use of it. In this era of oncoplastic breast surgery (OPS) reincorporation of ipsilateral ALND deserve rethinking. The Level 2 OPS breast-conserving surgery has 3 steps, step-1: oncologic resection of 20–50% breast tissue and a part of redundant breast skin with partial mastectomy, step-2: ipsilateral breast reconstruction using volume displacement and sometime volume replacement techniques, and step-3: contralateral symmetry surgery when volume displacement mastopexy performed. Replacement of step 3 of Level 2 OPS with ipsilateral ALND and breast skin sparing surgery might induce spontaneous and fair enlargement of the reconstructed smaller breasts within months due to lymphedema effect, and an appreciable improvement of ptosis status . Preserved redundant skin of the breast should provide room for enlargement to achieve original size. Thus ALND should de-escalate contralateral symmetry surgery workload of Level 2 OPS, necessity of plastic surgeon involvement in reconstruction procedure, costs of mastopexy of contralateral normal breast, conserve the natural beauty and functions of normal breast 3 , importance of protracted training programs of OPS, and magnitude of immediate post-operative complications and contracture of OPS. Thus help standardization of easier and safer OPS, and improved patient aesthetic outcome. A universal question always asked by BC patients that how many days she could survive after completing treatment. The attending oncologist try to answer that question based on findings of different prognostic factors of BC. The pathological node (pN) stage of Tumor, lymph Node, and Metastasis (TNM) staging system of International Union against Cancer (UICC) published by the American Joint Committee on Cancer (AJCC) 4 , 5 has introduced positive axillary lymph node (LN) count that could forecast subjective outcome (prognosis) BC 6 . The presence of any axillary LN metastasis (+ ve LN), and the number of + ve LNs determines pN stage of BC 7 are (1) stage pN0 when no + ve LN, (2) pN1 when 1–3 + ve LNs, (3) pN2 when 4–9 + ve LNs and (4) pN3 when ≥ 10 + ve LNs 8 . Accordingly, BC patients with pN0 stage should have best prognosis with probable long survival and pN3 patients should have worst prognosis with short survival. Prognosis of early stage BC without axillary LN metastasis (-ve LNs) is favorable and + ve LNs is less favorable. The current thought is that more the number of + ve LNs identified the worse is long term survival 9 . The pN stages should powerfully forecast the subjective outcome of treated BC patient the end-point of which is either recurrences or deaths. The disease free survival (DFS) and overall survival (OS) of BC should be long in pN0 and shortest in pN3 stages that is number of recurrence or deaths should be lowest in pN0 and highest in pN3 subgroup at a particular time interval. It might be possible that pN staging should anticipate prognosis of the BC patients with precision. The aims of study were to indicate practical clinical outcome of treated BC patients based on pN stages and lymph node ratio (LNR) subgroups. The objectives of this study were to (1) standardize Level 2 OPS by adding ipsilateral ALND and avoid contralateral symmetry surgery, (2) the number of BC patients presented in different pN stages and LNR subgroups, (3) the distribution of number of recurrences and deaths and (4) DFS and OS of different subgroups at a defined follow-up date, and (5) survival functions estimates of pN stages and LNR subgroups after deaths of all patients of any one subgroup. This study should indicate alternative standard of Level 2 OPS and ability to forecast prognosis by pN stages of BC patient. Methods This prospective cohort study was conducted on 51 consecutive BC patients diagnosed and treated in Ahsania Mission Cancer and General Hospital, Dhaka, Bangladesh. The study period was from August 2016 through December 2019. The patient’s information was collected from documents in the hospital registry using a pretested research instrument after obtaining approval from the ethical board of Ahsania Mission Cancer & General Hospital, Plot # 03, Embankment Dive way, Sector-10, Uttara Model Town, Dhaka-1230, Bangladesh and informed consent of the patients. All patients who underwent BC surgery with ALND in afore said institution and maintaining follow-up from the date of enrolment were included in this study and those had distant metastasis at the time of diagnosis were excluded. Modified radical mastectomy of Patey is a nationally recommended routine surgical procedure for BC and all methods were performed in accordance with the national guidelines and regulation. Data of basic sociodemographic, tumor characters, intervention and outcome related variables were collected. Data collected on BC stage according to TNM staging of 8th edition, types of surgical treatment given, pathological tumor (pT) stage (the greatest dimension in centimeter of a single tumor and larger or largest tumor of multifocal / multicentric BC cases), total axillary lymph nodes (ALNs) and + ve ALNs (presence of any BC cell deposit within ALNs) counts, LNR (i.e. ratio of positive to dissected ALNs), pN stages (i.e. pN0, pN1, pN2, and pN3 stage) of TNM staging of BC 10 , LNR subgroups, date of diagnosis of BC by fine needle aspiration cytology or histology (start-point of OS), date of surgical treatment of BC (start-point of DFS), date of diagnosis of recurrence (end-point of DFS) and deaths (end-point of OS), DFS and OS in months, site of recurrence (local or metastatic), cause of death (breast cancer specific or other causes). If recurrence or death of patients didn’t occurred during study period or they were lost to follow-up at the last known contact was indicated as censored. Data were analyzed according to 2 follow-up dates: (1) last follow-up date of July 22, 2025 for OPS cases and (2) for assessment of BC prognosis on December 2022 because at that follow-up date death of all patients belonging to high-risk LNR subgroup had occurred. Follow-up study should continue further. Median and mean age of the patients were 48 and 47.29 ± 9.84 (28–75) years respectively. Female patients were 50 (98%), mean height was 1.52 ± 0.07 (1.4–1.78) meters. Median and mean weight were 59 and 59.16 ± 10.59 (35–103) kg respectively and mean body mass index was 25.71 ± 4.47 (14.2–40.23) kg/m 2 . This data was published in an earlier report 11 . The –ve LN cases were 13 (25.5%) and + ve LN cases 38 (74.5%). Median and mean ALNs dissected were 12 and 13.33 ± 5.23 (6–26) LNs. Number of ALNs removed within range of 6 to 9 was 11 (21.6%), 10 to 15 was 27 (53.1%), 16 to 20 was 7 (13.73%), and 21 to 26 was 6 (11.76%). Median and mean number of + ve LNs were 3 and 4.04 ± 4.67 (0–20) LNs. Median and mean number of + ve LNs in Surgery-First group were 4 and 5.37 ± 4.69 (1–20) LNs and of NAC-Surgery group were 4.33 and 4 ± 3.12 (0–8) LNs respectively. This data was published in another earlier report 3 . LNR divided into low (≤ 0.2) -, intermediate (0.21–0.65) - and high-risk (> 0.65) subgroups according to cut-off value of a previous published report 3 . All treated BC patients were included. MRM performed in majority of cases. Most cases of ALND is accomplished by Level I and II and in selected cases Level III dissection. In Level 2 OPS cases step-2 volume displacement technique of cancer bearing breast done using periareolar two concentric circular incision. The inner circular incision was put outside the nipple-areolar complex and de-epithelialization done in between incisions. Then undermining of skin were attained to release breast tissue to allow adequate mobilization for safe excision of cancer and reshaping of breast. Partial mastectomy done to remove the malignant tumor and a margin of healthy tissue around it resulting in excision of > 20% of breast tissue. Redundant breast skin is preserved to provide room for future enlargement of breast and achievement of original size. The remaining adequately mobilized breast tissue were repositioned to fill-up the cavity created by tumor excision. The cavity is marked with vascular clips around the wall. Thus a new smaller breast is created with almost natural shape along with some improvement of degrees of ptosis. Ipsilateral ALND done through a separate small incision at the upper end of anterior axillary fold for lymphedema effect on reconstructed breast, pN staging, and LNR sub-grouping. In all 3 OPS cases reduction mammoplasty of opposite normal breasts were avoided. All other adjuvant therapy offered according to highly individualized protocol of BC treatment. The sliced mastectomy specimen and axillary soft tissue were fixed in 10% neutral buffered formalin maintaining and recording cold ischemic time. The specimen send to pathology laboratory where grossing of the specimen was performed by the pathologist according to set protocol. Tissue blocks taken were (1) four blocks from breast tumor, (2) one each from skin and nipple and (3) of any multifocal/multicentric tumor, (4) one or two from non-tumorous area of breast, (5) one each from deep and peripheral resection margins, (6) two from each > 2 cm ALNs and (7) one from each of other resected LNs. The blocks were processed for routine paraffin embedding. Sections were cut at 5µ thickness and stained with routine H and E staining methods. After mounting in a slide were examined microscopically by pathologist. Immunohistochemistry performed on tumor tissue and a combined reports provided. Statistical analysis was performed using SPSS version 23 (IBM Corp, USA). Mean was expressed as mean ± SD (minimum-maximum). Median values were recorded when possible to provide an accurate picture of distributions. Student’s t-test was used for continuous and chi-square test for categorical variables, ANOVA, Kaplan-Meier survivability estimate with log-rank test, and univariate and multivariate analysis of Cox regression model of fit done to assess survival outcomes and to identify significance. P < 0.05 with 95% confidence interval (CI) were considered statistically significant. Results Out of three nipple-areola-breast skin sparing OPS plus ipsilateral ALND two (4%) patients were alive till last follow-up on June 2025 and one (2%) patient died on November 2020. Both survivors were pre-menopausal woman one is overweight and other of healthy weight. The operation included complete oncologic resection and partial mastectomy, ipsilateral reconstruction using volume displacement technique through circumareolar double Doughnut incision without removal of redundant skin of breast and contralateral symmetry surgery. Ipsilateral ALND done as an additional procedure. The tumors were pT1 stage, hormone receptors positive, and Her 2 negative. Both patients received adjuvant chemo-, radiation- and antihormone-therapy. Their mean disease free survival were approximately 6 years according to last follow-up date. The dead postmenopausal woman of OPS was 45 years old had single tumor of 3 cm size involving right breasts of infiltrating ductal carcinoma grade II, > 25% breast tissue along with tumor was removed using Level 2 displacement OPS preserving extra skin-nipple-areola of breast and ipsilateral ALND, however, did not received required adjuvant chemo-, radiation-, antihormone-, or targeted-therapy. She had 22 axillary lymph nodes and 4 were positive, progesterone receptor and Her 2 positive, and disease free and overall survival were 15.4 and 19.7 months respectively. The operated breast was free of recurrence, and death was due to widespread bilateral pulmonary and hepatic metastasis. All three OPS cases achieved enlargement of operated breasts leading to spontaneous symmetrisation (Figs. 1 and 2). The number of cases belonged to pN0, pN1, pN2, and pN3 were 13 (25.5%), 16 (31.4%), 18 (35.3%), and 4 (7.8%) and of low-, intermediate-, and high-risk LNR were 23 (45.1%), 19 (37.3%), and 9 (17.6%) respectively (Table 1 ). The difference was highly significant between pN stages and LNR subgroups ( p < 0 . 000001 ). The median and mean duration of follow-up (according to December 2022) were 55.30 and 53.04 ± 15.66 (15.60-81.23), of DFS 51.11 and 47.58 ± 16.70 (13.6-73.63), and of OS 52.43 and 50.95 ± 14.69 (15.57–74.80) months respectively. Total number of recurrences were 17 (33.3%) and 34 (66.7%) were censored of them 6 (17.65%) cases were dropped out (censored unrelated to the study during follow-up period). Number of deaths were 21 (41.18%). The distribution of recurrences of pN0, pN1, pN2, and pN3 of total were 2 (3.9%), 5 (9.8%), 9 (17.6%) and 1 (2%) cases respectively with no significant difference ( p = 0 . 232 ). The number of recurrences of low-, intermediate-, and high-risk LNR of total were 6 (11.8%), 5 (9.8%), and 6 (11.8%) respectively (Table 1 ) with no significant difference ( p = 0 . 065 ). Total number of deaths were 21(41.20%). The median and mean duration of DFS of death cases were 39.60 and 35.44 ± 17.63 (1.3–59.50) and of OS were 46.12 and 44.02 ± 17.80 (15.57–74.80) months respectively. The distribution of deaths among pN0, pN1, pN2, and pN3 out of total were 3 (5.9%), 5 (9.8%), 10 (19.6%), and 3 (5.9%) respectively with no significant difference ( p < 0.12 ). The death distribution among low-, intermediate- and high-risk LNR were 6 (25%), 5 (26.32%), and 9 (100%) respectively (Table 1 ) with significant difference ( p = 0.000393 ). Distribution of deaths among pN and LNR subgroups was significant ( p < 0 . 013 ). The estimate mean survival time of DFS for pN0, pN1, pN2, and pN3 were 59.4 (CI 55.7 and 63.2), 59.6 (CI 47.8 and 71.4), 48.5 (CI 36.6 and 60.3), and 46.7 (CI 39.6 and 53.0) months respectively. Estimated median survival time of DFS for pN2 was 50.4 (CI 34.7 and 66.2) months. Pair wise comparisons (Log Rank test) of DFS for pN stages indicated no significant difference between pN0, pN1 and pN3 except between pN0 and pN2 ( p = 0 . 048 ). However, survival functions curve of DFS for pN0 indicated best possible survival time while curves of pN1, pN2 and pN3 were similar and indicated worst survival time (Fig. 3). The estimate mean survival time of DFS for low-, intermediate-, and high-risk LNR were 58.6 (CI 52.8 and 64.3), 63.8 (CI 54.6 and 73.1), and 23 (CI 14.1 and 31.9) months respectively. The estimate median survival time of high-risk LNR was 16.2 (CI 8.8 and 23.6) months. Pair wise comparison (Log Rank) indicated highly significant difference between low- and intermediate- risk ( p = 0.003 ), low- and high-risk ( p = 0 . 000003 ) and intermediate- and high-risk LNR ( p = 0.000115 ). The curves of low- and intermediate-risk LNR were similar with best, and high-risk LNR with worst survival time (Fig. 4). The estimate mean survival time for OS of pN0, pN1, pN2 and pN3 subgroups were 62.61 (95% CI were 57.89 and 67.34), 66.61 (95% CI 59.14 and 74.08), 52.77 (95% CI 43.73 and 61.81), and 53.18 (95% CI 26.08 and 80.28) months respectively. The estimate median survival time for OS of pN2 and pN3 were 62.13 (95% CI 45.35 and 78.91) and 40.73 (95% CI 6.48 and 74.98) months respectively. Overall comparison (Log Rank test) of survival function indicated no significant difference of OS of pN stages (Log rank test, p = 0 . 068 ). Pair wise comparisons indicated significant difference between pN0 and pN2 ( p = 0 . 048 ) for OS and no significant difference were observed among pN0 and pN1 ( p = 0 . 891 ), pN0 and pN3 ( p = 0 . 10 ), pN1 and pN2 ( p = 0 . 058 ), pN1and pN3 ( p = 0 . 139 ), and pN2 and pN3 ( p = 0 . 863) . The survival function estimator of OS indicated curves of pN0 and pN1 were similar and the best survival time. On the other hand curves of pN2 and pN3 had similar but the worst survival time (Fig. 5). The estimate mean survival time of OS for LNR of low-, intermediate-, and high-risk LNR were 68.21 (95% CI 60.97 and 75.93), 68.50 (95% CI 62.08 and 74.93), and 37.35 (95% CI 23.54 and 51.15) months respectively. The estimate median survival of low- and high-risk LNR were72.63 (95% CI 5.75 and 89.51) and 27.7 (95% CI 12.13 and 43.27) months respectively. Overall comparisons (Log Ran test) of survival functions of OS of LNR group indicated highly significant difference ( p = 0.000006 ). Pair wise comparisons of OS indicated significant difference between low- and high-risk LNR ( p = 0 . 000041 ), and intermediate- and high-risk LNR ( p = 0 . 000161 ). There was no significant difference between low- and intermediate-risk LNR ( p = 0 . 819 ). The survival function estimator plots for OS indicated curves of low- and intermediate-risk LNR were similar with the best possible survival time. On the other hand curve of high-risk LNR indicated the worst survival time (Fig. 6). The variables like age in years, menopausal age groups, body weight, BMI, BMI categories, number of multicentric/multifocal breast tumor, maximum diameter of the tumor, pT stages, total number of ALNs dissected, number of positive ALN, histological grade, pN stages, LNR, LNR subgroups, ER, PR and Her-2 receptor, TNM stage group, and NAC status were analyzed using Cox regression model of fit. The univariate analysis of aforesaid covariates of DFS of BC of pN stages with statistical significance were of BMI categories (ß = 0.693, p = 0 . 039 , HR = 1.99, CI of HR 1.036 and 3.859),LNR (ß = 2.408, p = 0 . 003 , HR = 11.109, CI of HR 2.286 and 53.995), LNR subgroups (ß = 1.221, p = 0 . 003 , HR = 3.391, CI 1.531 and 7.51), Her-2 positive BC (ß = 2.085, p = 0 . 000264 , HR = 8047, CI 2.625 and 24.69), and NAC status (ß = 1.453, p = 0 . 005 , HR = 4.276, CI for HR 1.564 and 11.691). However, variables like age, pre- and post-menopausal age group, body weight, BMI, number of tumor in the breast, maximum diameter of the tumor, total ALN and positive ALN counts, pN stage, histological grade, ER and PR positivity, and TNM stage grouping were not significant. The multivariate Cox regression analysis of covariates for DFS were BMI categories, LNR and LNR subgroups indicated statistical significant goodness of fit of the variables in the model [ꭓ 2 (6) = 22.8, p = 0 .001] and independent predictor variables were found to be Low-risk LNR ( p = 0 . 012 ), Intermediate-risk LNR (ß = -5.434, p = 0 . 044 , HR = 0.004, CI 0.000022 and 0.873), and High-risk LNR (ß = -4.861, p = 0 . 008 , HR = 0.008, CI 0.00021 and 0.286). Univariate analysis of Cox regression model of fit for covariates of OS of BC with statistical significance were pT stages (ß = 0.798, p = 0 . 03 , HR = 2.222, CI of HR 1.08 and 4.569), number of positive LNs (ß = 0.077, p = 0 . 022 , HR = 1.08, CI of HR 1.011 and 1.154), pN stages (ß = 0.491, p = 0 . 044 , HR = 1.634, CI 1.013 and 2.636), LNR (ß = 2.048, p = 0 . 001 , HR = 7.751, CI 2.238 and 26.837), LNR subgroups (ß = 1.071, p = 0 . 001 , HR = 2.02, CI 1.533 and 5.56), Her 2 positive BC (ß = 2.075, p = 0 . 000073 , HR = 7.965, CI of HR 2.856 and 22.209), TNM stage grouping (ß = 0.239, p = 0 . 036 , HR = 1.269, CI 1.015 and 1.587) and NAC status (ß= 1.188, p = 0 . 012 , HR = 3.280, CI 1.298 and 8.289). The variables like age in years, pre- and post-menopausal age group, body weight, BMI, number of tumor in the breast, maximum diameter of tumor, histological grade, dissected ALN counts, ER and PR positivity were not statistically significant as covariates of OS of BC. Model coefficients of multivariate analysis of Cox regression survival model of OS of pT stages, number of positive ALNs, pN stages, LNR, LNR subgroups, and TNM stage grouping indicated significant goodness of fit when the model included this variables [ꭓ 2 (16) = 41.741, p = 0 . 000431 ] and independent covariates were Low-risk LNR ( p = 0 . 007 ), Intermediate-risk LNR (ß = -9.468, p = 0 . 019 , HR = 0.000077, CI 0.000 and 0.213), and High-risk LNR (ß = -9.009, p = 0 . 005 , HR = 0.000122, CI 0.000 and 0.07). Discussion Nowadays Level 2 OPS is most frequent surgical modality of treatment of BC 12 which is a combination of excision of the malignant breast tissue with at least 0.5 mm margin of surrounding healthy tissue and plastic surgery techniques for immediate reconstruction and symmetry surgery performed by reduction mammoplasty of opposite normal breast. On the other hand every surgical oncologist aware of the lymphedema of the upper extremity and pectoral region including leftover breast as a complication of ALND. Thus we can easily utilize the breast lymphedema of ALND as an alternative mechanism of spontaneous enlargement of the operated cancer-bearing reconstructed small breast instead of reduction of size of opposite normal breast. It should be expected that easier ipsilateral ALND compared to popular reduction mammoplasty of contralateral normal breast should be attractive routine alternative in OPS 3 because of skin sparing OPS with ipsilateral ALND developed a good looking scar free enlargement of operated cancer bearing breasts, create a more natural looking breast mound, maintain intact sensation and capability of lactation in every individual cases, and improvement of patient’s self-esteem and body image. This study observed significantly sizeable number of high risk cases were included in high-risk LNR subgroup compared to that of pN3 stage ( p < 0.001 ) of BC patients. LNR is a better predictor of prognosis than pN stage was observed in other study 13 . Overall comparisons of DFS indicated no significant difference of survival functions ( p = 0.074 ) in pN stages and highly significant difference in LNR subgroups ( p = 0.000006 ). Pair wise comparison of survival functions of DFS of pN subgroups indicated significant difference of pN0 with pN3 ( p = 0.006 ) and with pN2 ( p = 0.018 ), and survival plots of DFS indicated similar curves of pN1, pN2, and pN3 with no statistically significant difference between them. Thus pN0 of pN stage can well assess good prognosis with long survivability and on the other hand pN1, pN2 and pN3 made vague assessment of worst prognosis. The overall comparisons of survival functions of DFS of LNR indicated better expression with high precision of survival time ( p = 0 . 000066 ) than pN staging ( p = 0 . 068 ). Pair wise comparisons indicated highly significant difference of survival functions of DFS was observed between low- and high-risk LNR ( p = 0 . 000001 ), and intermediate- and high-risk LNR ( p = 0 . 000161 ) and no significant difference between low- and intermediate-risk LNR ( p = 0 . 772 ) indicated very high precision of DFS. The survival plots of low- and intermediate-risk LNR of DFS curves are similar indicating better and that of high-risk LNR worst survivability. The better predictive power of LNR than pN stages of DFS of BC patients was observed in a retrospective study 6 . Overall comparison of survival functions of OS of pN stage indicated no significant difference ( p = 0 . 068 ) and that of OS of LNR group significant difference ( p = 0 . 000006 ). Pair wise comparisons of survival function of OS of pN stage indicated significant difference between pN0 and pN2 ( p = 0 . 048 ), and no significant differences between pN0 with pN1and pN3, as well as pN1 with pN2 and pN3. The curves of the survival plot of pN1, pN2, and pN3 were similar indicating pN staging discriminate vague prognosis thus counting positive axillary lymph node only is not enough for prognostication. On the other hand, no significant difference of survival function of OS was observed between low- and intermediate-risk LNR subgroups ( p = 0 . 819 ) and their curves in the survival plot were similar too indicating best and high risk LNR subgroup had worst survival time. Pair wise comparisons of OS indicated significant difference between low- and high-risk LNR subgroups ( p = 0 . 000041 ), and that of intermediate- and high-risk LNR subgroups ( p = 0 . 000161 ). High-risk LNR subgroup had worst survival time. It is indicated that prognostication of BC using LNR could be possible with precision fulfilling mandatory requirement of ALND. One retrospective study of OS indicated LNR is superior to pN stage for the determination of BC prognosis 14 and another meta-analysis indicated high LNR value is associated with short OS of BC patients after neoadjuvant chemotherapy 15 . The reality is with the increased rate of detection of early BC (T1, T2) after introduction of screening program (40% T1 and 30% T2) 16 resulting in improvement of breast cancer-associated mortality 17 and increased procedures of sentinel lymph node biopsy (SLNB) along with declined number of ALND because of node staging of TNM classification require positive LN counts only. One study in China indicated the use of ALND declined from 94% on 1998 to 36% on 2004 in breast cancer surgery 18 . Another study in Spain indicated rate of ALND was 91% in 1998 that decreased to 34% within 2017 19 . There is progressively increased rate of detection of number of positive lymph nodes after introduction of SLNB due to significantly increased detection of micrometastasis form through pathological examination. Currently surgical oncologists of breasts cherishing the idea that ALND should be a selective operation. On the other hand, gastrointestinal (GI) oncologist give importance to extensive systemic LN dissection for carcinoma of the esophagus, stomach and colon. An analysis of Surveillance, Epidemiology, and End Results database showed that calculated OS increased by 7.6% for T1/2N0, 11% for T3N0, and 7% for T3N1 for every additional 10 LNs dissected which could be up to a cut point at 40 dissected LNs and data provided support in favor of extended lymphadenectomy for superior survival 20 . Comprehensive lymphadenectomy is a routine procedure in cases of GI carcinomata. Thus axillary lymphadenectomy should be a routine procedure irrespective of nodal status because of BC is an adenocarcinoma. This small scale prospective study indicated some important observations deserving large scale research. There is no national breast screening program in this country. Pair wise comparisons of survival functions indicated no significant difference between low- and intermediate-risk LNR in DFS ( p = 0.772 ) and OS ( p = 0.819 ). Survival functions estimator curves of DFS and OS also indicated low- and intermediate-risk LNR were similar although current study credited to three LNR risk groupings 3 . Above findings indicated that intermediate-risk should be incorporated in the low-risk LNR subgroup and LNR should be classified into low- and high-risk. Low- and high-risk LNR subgrouping was also adapted in other study 21 . The overall Cox regression model of fit for DFS indicated statistically significant ( p = 0.001 ) improvement of the model after addition of following covariates and efficiently explained the data. Negative regression coefficient (ß) of the variables like age in year ( p = 0 . 02 ) and the number of positive pN ( p = 0 . 039 ) were observed statistically significant indicating that these covariates improved prognosis with their increments. One study indicated younger BC age group exhibit more aggressive disease than older patient 22 and higher number of positive LNs were associated with shorter DFS 23 . Positive ß were observed in post-menopausal age group, BMI, tumor diameter, number of dissected LNs, LNR, TNM stage grouping, and NAC status. Statistically significant increase of recurrences of BC or decreased DFS of postmenopausal women ( p = 0 . 025 ) was observed in his study indicated an association with the number. Similar result was observed in other study 24 . Statistically significant positive ß of BMI ( p = 0 . 024 ) of this study indicated obese patients experienced worst DFS and was similar to that of other observations 25 . With the increase of pT stage ( p = 0 . 007 ) there was increased hazard rate, increased recurrence and decreased DFS. Similar result was observed in other study 26 . Regression coefficient (ß) of histological grade was slightly positive indicating that increased histological grade there was slight increase of recurrence rate. However, the effect was minimal. LNR subgroups significantly fit in the model ( p = 0 . 002 ) and indicated longer DFS in low-risk LNR than high-risk LNR. Similar result was observed in other study 27 . All NAC treated BC patients of this study had partial pathological response and indicated statistically significant decreased DFS ( p = 0 . 0000183 ) compared to the patients who did not received NAC. Similar result was also observed in other study 28 . Intermediate- ( p = 0.044 ) and high- risk ( p = 0.008 ) LNR were observed as independent covariates like that of other study 27 . The overall Cox regression model of fit for OS indicated statistically significant ( p = 0 . 000038 ) improvement of the model after inclusion of following defined covariates and efficiently explained the data. Slightly negative regression coefficient was observed for age in year, indicating that lower age is associated with higher hazard rate of OS, however, the effect is not statistically significant. Similar result was observed in another study 29 . Statistically significant negative ß was observed with Her 2 positive status ( p = 0.000073 ) indicating association with decreased hazard rate thus increased OS. Similar result observed in other study 30 . Statistically significant positive regression coefficient were observed with LNR ( p = 0 . 001 ), indicating that as LNR increased hazard rate increased significantly and OS decreased. Similar result observed in other study 27 . Positive regression coefficient of number of patients receiving NAC was significant ( p = 0 . 012 ) indicated that increased number of events (deaths) were associated with increased number of NAC patients compared to those not receiving NAC. Similar result observed in other study 31 . Positive regression coefficient with no statistical significance were observed with age group ( p = 0 . 0264 ), body weight ( p = 0 . 11 ), BMI ( p = 0 . 062 ), number of breast tumors ( p = 0 . 798 ), maximum diameter of the tumor ( p = 0 . 263 ), histological grade ( p = 0 . 387 ), total number of dissected LNs ( p = 0 . 335 ), ER ( p = 0 . 317 ), and PR ( p = 0 . 551 ). The multivariate Cox regression model analysis indicated that low-risk LNR was associated with increased DFS and OS. On the other hand intermediate- and high- risk LNRs were associated with decreased DFS and OS indicating ALND forecasts prognosis of breast cancer with precision. Similar result was observed in other study 27 . Conclusions Ipsilateral axillary lymph node dissection should diminishes workload of Level 2 step 3 of contralateral symmetry surgery of normal breasts of oncoplastic surgery, involvement of plastic surgeons, and spares extra time of training program on account of simplicity. It decreases chances of post-operative complications like infection, scar formation and deformity of the contralateral normal breast. Long term follow-up report indicated promising result of this alternative procedure, however, sample size is very small. Those who are experts in minimally invasive surgery on breast cancer should come forward to re-evaluate endoscopic application of this alternative model for further improved standardization. Greater number of high-risk breast cancer cases were brought to light due to routine axillary dissection and calculation of lymph node ratio subgrouping, and found be a unique procedure to identify the best and worst prognosis with efficient discrimination. Study also observed that pathological node staging of TNM classification is a powerless predictor of prognosis of breast cancers. Axillary lymph node dissection for breast cancers is a unique independent predictor could sensibly discriminate good prognosis from bad and worst one with distinct precision. Consequently lymph node ratio should be incorporated as superscript of pathological node stages of TNM classification for breast cancer mentioning positive and total number of dissected lymph nodes. The counting of only positive axillary lymph nodes is insufficient to predict prognosis of breast cancer. Abbreviations AJCC: American joint committee on cancer ALND: Axillary lymph node dissection ALNs: Axillary lymph nodes ANOVA: Analysis of variance BC: Breast cancer ß: Regression coefficient for the variable CI: 95% confidence interval DFS: Disease free survival ER: Estrogen receptor FISH: Fluorescence in situ hybridization GI: Gastrointestinal Her2: Human epidermal growth factor receptor HR: Hazard ratio IBM: International Business Machine Corporation LNs: Lymph nodes LNR: Lymph node Ratio MRM: Modified radical mastectomy NAC: Neoadjuvant chemotherapy OPS: Oncoplastic surgery OS: Overall survival pN: Pathological node PR: Progesterone receptor SLNB: Sentinel lymph node biopsy SPSS: Statistical package for the social sciences TNM: Tumor, lymph Node, Metastasis UICC: International union against cancer Declarations Ethical approval and consent to participate: This research work was conducted after obtaining approval from the institutional ethical board and informed consent of the patients. Consent of publication: All authors consented for publication of this manuscript in the Breast Cancer Research. Availability of supporting data: This prospective research work is continuing its’ long-term follow-up study. The dataset used during current study are available from corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interest. Funding: There is no financial arrangement with anyone. Authors contributions: A. K. Mostaque contributed to the design of the experiment, performed all surgical interventions, collection of data of the patients, analysis and interpretation of data, continuing long term follow-up, and preparation of the paper. M. Kamal contributed designing pathological methodology, perform most of the histology and immunohistochemistry of the specimens and revising the manuscript. A.M.M. Shariful Alam contributed in collection of data, designing methodology, and repeated revision of manuscript. Acknowledgements: We acknowledge with sorrow the recent death of the author Professor Dr. M. Kamal due to liver cancer who contributed so much in designing pathological methodology, in preparation of histology and immunohistochemistry reports and revision of manuscript. References Freeman MD, Gopman JM, Salzberg CA. The evolution of mastectomy surgical technique: from mutilation to medicine. Gland Surg. 2018 [Accessed 1 January 2023];7(3):308 – 315. DOI:10.21037/gs.2017.09.07 Giuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, et al. Effect of axillary dissection vs no axillary dissection on 10-years overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017 [Accessed 9 April 2023];318(10):918-926. DOI: 10.1001/jama.2017.11470 Mostaque AK, Mamun MAA, Kamal M, Alam AMMS, Chowdhury IU. Oncoplastic surgery and outcome prediction deserve axillary lymph node dissection – treatment results of 51 cases of breast cancer. IISJ. 2021 [Accessed 11 June 2023];5(09):25-37. Available from https://iisj.in/index.php/iisj/article/view/344 Arnone P, Zurrida S, Viale G, Dellapasqua S, Montagna E, Arnaboldi P, et al. The TNM classification of breast cancer: need for change. Update Surg. 2010 [Accessed 31 January 2023];26:75 – 81. DOI: 10.1007/s13304-010-0014-y Sawaki M, Shien T, Iwata H. TNM classification of malignant tumors (Breast cancer study group). JJCO. 2019 [Accessed 29 January 2023];49 (3):228 -231. DOI: 10.1093/jjco/hyy182 Xiao XS, Tang HL, Xie XH, Li LS, Kong YN, Wu MQ, et al. Metastatic axillary lymph node ratio (LNR) is prognostically superior to pN staging in patients with breast cancer – results for 804 Chinese patients from a single institution. Asian Pac J Cancer Prev. 2013;14(9):5210–5223. DOI: https://dx.doi.org/10.7314/APJCP.2013.14.9.5219 Chang JM, Leung JWT, Moy L, Ha SA, Moon WK. Axillary nodal evaluation in breast cancer: state of the art. J Radiol. 2020 [Accessed 24 January 2023];295(3):500 – 515. https://doi.org/10.1148/radiol.2020192534 Safavi A, Kaviani A, Mohammadzadeh N, Zand S, Krag DN. Breast cancer prognostication by pathologic node staging (pN-staging) system versus lymph node ratio (LNR): A critical review of conflicts with number of nodes, Z-0011 trial, staging cut- points, neo-adjuvant therapy and survival estimation. Arch Breast Cancer. 2017;4(4):110-123. DOI: 10.19187/abc.201744110-123 Zhao X, Wei J, Li X, Tang H, Wang P, Cao S. Increasing negative lymph node count predicts favorable OS and DFS in breast cancer with different lymph node-positive subgroups. J PloS ONE. 2018;13(3):e0193784. DOI: https://doi.org/10.1371/journal.pone.0193784 Koh J, Kim MJ. Introduction of a new staging system of breast cancer for radiologists: An emphasis on the prognostic stage. Korean J Radiol. 2019 [Accessed 7 May 2023];20(1):69-82. DOI: 10.3348/kjr.2018.023 Mostaque AK, Mamun MAA, Alam AMMS, Chowdhury IU, Sharif RB. Assessment of anthropometric measurements, time lag between diagnosis and surgery, postoperative recovery time, and outcome of oncoplastic surgery of treated breast cancer patients. J MAR Oncol. 2022 [Accessed 13 Oct 2023];3(2):1-17. Available from: htpps://www. medicalandresearch.com Thompson PW, Chatterge A, Losken A. Standards in oncoplastic breast-conserving surgery. Ann Breast Surg. 2022 [Accessed 9 September 2024];6:37. DOI: 10.21037/abs-21-33 Ahn SH, Kim HJ, Lee JW, Noh DY, Yang JH, Jung SS, et al. Breast Cancer Res Treat. 2011 [Accessed 14 January 2024];130:507-515. DOI: https://doi.org/10.1007/s10549-011-1730-9 Wu S-G, He Z-Y, Li Q, Lin H-X, Guan X-X. Prognostic value of metastatic axillary lymph node ratio for Chinese breast cancer patients. J PloS ONE. 2013 [Accessed 12 June 2024];8(4):e61410. DOI: 10.1371/journal.pone.0061410 Liu J, Li Y, Zhang W, Yang C, Yang C, Chen L, et al. The prognostic role of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy: a doe response meta-analysis. Front Surg. 2022 [Accessed 12 June 2024];9:971030. DOI: 10.3389/fsurg.2022.971030 Eisemann N, Waldmann A, Kataliic A. Epidemiology of breast cancer – current figures and trend. Gaburtsilfe Feauenheilkd. 2013 [Accessed 22 December 2023];73(2):130-135. DOI: 10.1055/s-0032-1328075 Triev PDY, Mello-Thomas CR, Baron ML, Lewis SJ. Look how far we have come: BREAST cancer detection education on the international stage. Front Oncol. 2023 [Accessed 23 December 2023);12:1023714. DOI: 10.3389/onc.2022.1023714 Gou Z, Lu X, He M, Yu L. Trends in axillary surgery and clinical outcomes among breast cancer patients with sentinel node metastasis. The Breast. 2022 [Accessed 20 December 2023];63:9-15. DOI: 10.1016/j.breast.2022.02.014 Garcia-Novoa A, Acea-Nebril B, Casal-Beloy I, Garea CC, Gomez-Dovigo A, Builes-Ramirez S, et al. The decline of axillary lymph node dissection in breast cancer. Evolution of its indication over the last 20 years. J CIR ESP. 2019 [Accessed 24 December 2023];97(4):222-229). DOI: 10.1016/j.cir.eng,2019,01.018 Smith DD, Schwarz RR, Schwarz RE. Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database. J Clin Oncol. 2005 [Accessed 26 December 2023];23(28):7114-24. DOI: 10.1200/jco.2005.14.621 Soran A, Ozman T, Salamat A, Soybir G, Johnson R. Lymph node ratio (LNR): Predicting prognosis after neoadjuvant chemotherapy (NAC) in breast cancer patients. Eur J Breast Health. 2019 [Accessed 12 August 2024];15(4):249-255. DOI: 10.5152/ejbh.2019.4848 Chen H-I, Zhou M-q, Tian W, Meng K-x, He H-f. Effect of age on breast cancer patient prognosis: A population-based study using the SEER 18 data base. PloS ONE. 2016 [Accessed 9 ay 2025];11(10):e0165409. doi: 10.1371/journal.pone.0165409 Tonellotto F, Bergman A, de Souza Abraháo K, de Aguiar SS, Bello MA, Thuler LCS. Impact of number of positive lymph nodes and lymph node ratio on survival of women with node positive breast cancer. Eur J Breast Health. 2019 [Accessed 14 ay 2025];15(2):76 – 84. doi: 10.5152/ejbh.2019.4414 Xie Y, Deng Y, Wei S, Huang Z, Li L, Huang K et al. Age has a U-shaped relationship with breast cancer outcomes in women: a cohort study. Front Oncol.2023 [Accessed 15 May 2025];13:1265304. doi: 10.3389/fonc.2023.1265304 Zangouri V, Balaneji SS, Golmoradi R, Kafili E, Bologhi S, Mousavi SA et al. Effects of BMI on prognosis, disease-free survival and overall survival of breast cancer. BC Cancer. 2025 [Accessed 16 May 2025];25:257. doi: https://doi.org/10.1186/s12885-025-13638-7 Liu Y, He , Zuo W-J, Hao S, Wang Z-H, Shao Z-M. Tumor size still impacts prognosis in breast cancer with extensive nodal involvement. Front Oncol. 2021 [Accessed 16 May 2025];11:585613. doi: 10.3389/fonc.2021.585613 Solac M, Turkoz FP, Keskin O, Aksoy S, Babacan T, Sarici F e al. The Lymph node ratio as an independent prognostic factor for non-metastatic node-positive breast cancer recurrence and mortality. JBUON. 2015 [Accessed 19 May 2025];20(3):737-745. PMID: 26214625 Gentile D, Sagona A, Camillia CD, Fernandes B, Barbieri E, Grimaldi SD et al. Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients. J Breast.2023 [Accessed 20 May 2025];69:323-329. doi: htpps://doi.org/10.1016/j.breast.2023.03.016 Sbaity E, Tamim H, Fuleihan G E-H, Abbas J, Zahwe M, Sayed RE et al. Effect of young age (below 40 years) on oncologic outcomes in Lebanese patient with breast cancer: a matched cohort study. BMC Cancer. 2024 [Accessed 25 May 2025];24:560. doi: https://doi.org/10.1186/s12885-024-11910-w Löb S, Linsmeier E, Herbert SL, Schlaiß T, Kiesel , Wischhusen J et al.Prognostic effect of Her2 evolution from primary breast cancer to breast cancer metastases. J Cancer Res Clin Oncol. 2023 [Accessed 26 May 2025];149(8):5417-5428. doi: 10.1007/s99432-922-94486-0 Table 1 Table 1 is available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-7316406","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":508910065,"identity":"f651e00a-9117-40ee-92ee-57165fde533a","order_by":0,"name":"A. K. Mostaque","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYFAD/vaDDxgYDhCllrEBTEmcSTYgUQtDgpkEUVp029ufP/hRdliOv+FAWjVPzR05fgbmh49u4NFiduaMYWPPucPGEocbj93mOfbMWLKBzdg4B5+WGzmMDbxthxMbDhxIu83DdjhxwwEeNmn8WtIfNv5tO1w//0CCWTHPP6K0JBg2A21JMABqYQZZR1gL0C+zZc6lG268cSZZcm7fYWPJZkJ+Od7+4OObMmt5ufPtBz+8+QYMOvbmh4/xaYEANgjFxAMimQkqR9LC+IMo1aNgFIyCUTDSAABV8VdgiUgx6QAAAABJRU5ErkJggg==","orcid":"","institution":"Gonoshayastha Somajvittik Medical College","correspondingAuthor":true,"prefix":"","firstName":"A.","middleName":"K.","lastName":"Mostaque","suffix":""},{"id":508910066,"identity":"861a0528-569b-4860-9111-96f407386c4c","order_by":1,"name":"M. Kamal","email":"","orcid":"","institution":"Bangabandhu Sheikh Mujib Medical University","correspondingAuthor":false,"prefix":"","firstName":"M.","middleName":"","lastName":"Kamal","suffix":""},{"id":508910067,"identity":"a924250b-32b1-4d09-9965-e873784f12c3","order_by":2,"name":"A. M. M. Shariful Alam","email":"","orcid":"","institution":"Ahsania Mission Cancer and General Hospital","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"M. M. Shariful","lastName":"Alam","suffix":""}],"badges":[],"createdAt":"2025-08-07 08:23:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7316406/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7316406/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90544381,"identity":"fcb56bfd-9e05-49b2-bb0b-8a6de149c6d8","added_by":"auto","created_at":"2025-09-04 00:18:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":5996267,"visible":true,"origin":"","legend":"\u003cp\u003eImage of first case of oncoplastic surgery with ipsilateral axillary dissection.\u003c/p\u003e\n\u003cp\u003eA 40 years old female cancer survivor presented with a 2 cm size infiltrating ductal carcinoma grade-II at upper outer quadrant of left breast of pN0 stage after excision of \u0026gt;20% breast tissue including tumor. There is noticeable improvement of breast ptosis with minimal edema at pectoral and shoulder region, subtle edema of left upper extremity and perfect breasts symmetrisation. Image taken 20\u003csup\u003e.\u003c/sup\u003e73 months after surgery.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7316406/v1/47c8b18ef48bbd53fd182fd9.png"},{"id":90544388,"identity":"f55ab071-384c-43d4-bb1a-0bbb79e5eec7","added_by":"auto","created_at":"2025-09-04 00:18:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11460503,"visible":true,"origin":"","legend":"\u003cp\u003eImage of second case of oncoplastic breast surgery plus ipsilateral axillary dissection.\u003c/p\u003e\n\u003cp\u003eA 38 years old cancer survivor presented with 1\u003csup\u003e.\u003c/sup\u003e8 cm size recurrent residual infiltrating ductal carcinoma grade-II at upper outer quadrant of left breast .One positive node out of 22 axillary nodes dissected and about 25% breast issue with tumor was excised. Image taken 19.27 months after surgery.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7316406/v1/276cd667795bc3d58c4e1c62.png"},{"id":90545200,"identity":"83edd012-39a0-4ea6-9b1d-eae9871e94c8","added_by":"auto","created_at":"2025-09-04 00:34:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":296035,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival Functions of DFS of pN stages of treated breast cancer patients.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7316406/v1/f3bd59f1c5d3d390bde091bc.png"},{"id":90544384,"identity":"b6c00270-2faf-43fc-92cc-ad91886db290","added_by":"auto","created_at":"2025-09-04 00:18:23","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":271967,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival Functions of DFS of LNR groups of treated breast cancer patients.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7316406/v1/7dd6effbd8bb23af85912665.png"},{"id":90545053,"identity":"a1bcc036-f137-4a00-9fb4-94697148d640","added_by":"auto","created_at":"2025-09-04 00:26:23","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":287297,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival Functions of OS of pN groups of treated breast cancer patients.\u003c/p\u003e","description":"","filename":"Fig5.png","url":"https://assets-eu.researchsquare.com/files/rs-7316406/v1/0c9b11bd060f589b905b692f.png"},{"id":90544390,"identity":"f31591cf-218e-43e3-ba60-c45a995ab1c7","added_by":"auto","created_at":"2025-09-04 00:18:23","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":268699,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival unction of OS of LNR groups of treated breast cancer patients.\u003c/p\u003e","description":"","filename":"Fig6.png","url":"https://assets-eu.researchsquare.com/files/rs-7316406/v1/6d2398fb608da46839339986.png"},{"id":92375917,"identity":"20c948af-d3b3-48de-8f0c-9aed04576a73","added_by":"auto","created_at":"2025-09-29 04:47:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":27627068,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7316406/v1/09160335-3fd4-4faf-944e-1e25a8cd4a18.pdf"},{"id":90544373,"identity":"9e2afc0a-ea75-4f5c-897f-89ccea557221","added_by":"auto","created_at":"2025-09-04 00:18:23","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16270,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7316406/v1/8ffd0b4adffc92db0226c31d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"De-escalation of oncoplastic surgery and prediction of breast cancer survival beyond serial axillary dissection – A prospective study","fulltext":[{"header":"Background","content":"\u003cp\u003eMichael Servetus (1509\u0026ndash;1533 AD) was the first to introduce ipsilateral axillary lymph node dissection (ALND) with removal of breast tumors and a portion of pectoralis muscles. This surgical method was followed for 300 years and Halsted (1852\u0026ndash;1922) made it popular \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAfter introduction of the radiotherapy as multimodality treatment of breast cancer (BC) therapeutic role of ALND was disregarded \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Currently occasional ALND is utilized as a therapeutic component of BC surgery and sentinel lymph node biopsy counts only positive axillary nodes for pN staging to forecast prognosis only. Though ALND is a simple procedure physicians focused on disadvantages \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e and surgeons put off thinking use of it. In this era of oncoplastic breast surgery (OPS) reincorporation of ipsilateral ALND deserve rethinking. The Level 2 OPS breast-conserving surgery has 3 steps, step-1: oncologic resection of 20\u0026ndash;50% breast tissue and a part of redundant breast skin with partial mastectomy, step-2: ipsilateral breast reconstruction using volume displacement and sometime volume replacement techniques, and step-3: contralateral symmetry surgery when volume displacement mastopexy performed. Replacement of step 3 of Level 2 OPS with \u003cem\u003eipsilateral ALND and breast skin sparing surgery might induce spontaneous and fair enlargement of the reconstructed smaller breasts within months due to lymphedema effect, and an appreciable improvement of ptosis status\u003c/em\u003e. \u003cem\u003ePreserved redundant skin of the breast should provide room for enlargement to achieve original size.\u003c/em\u003e Thus ALND should de-escalate contralateral symmetry surgery workload of Level 2 OPS, necessity of plastic surgeon involvement in reconstruction procedure, costs of mastopexy of contralateral normal breast, conserve the natural beauty and functions of normal breast \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e, importance of protracted training programs of OPS, and magnitude of immediate post-operative complications and contracture of OPS. Thus help standardization of easier and safer OPS, and improved patient aesthetic outcome.\u003c/p\u003e\u003cp\u003eA universal question always asked by BC patients that how many days she could survive after completing treatment. The attending oncologist try to answer that question based on findings of different prognostic factors of BC. The pathological node (pN) stage of Tumor, lymph Node, and Metastasis (TNM) staging system of International Union against Cancer (UICC) published by the American Joint Committee on Cancer (AJCC) \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e has introduced positive axillary lymph node (LN) count that could forecast subjective outcome (prognosis) BC \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. The presence of any axillary LN metastasis (+\u0026thinsp;ve LN), and the number of +\u0026thinsp;ve LNs determines pN stage of BC \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e are (1) stage pN0 when no\u0026thinsp;+\u0026thinsp;ve LN, (2) pN1 when 1\u0026ndash;3\u0026thinsp;+\u0026thinsp;ve LNs, (3) pN2 when 4\u0026ndash;9\u0026thinsp;+\u0026thinsp;ve LNs and (4) pN3 when \u0026ge;\u0026thinsp;10\u0026thinsp;+\u0026thinsp;ve LNs \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Accordingly, BC patients with pN0 stage should have best prognosis with probable long survival and pN3 patients should have worst prognosis with short survival. Prognosis of early stage BC without axillary LN metastasis (-ve LNs) is favorable and +\u0026thinsp;ve LNs is less favorable. The current thought is that more the number of +\u0026thinsp;ve LNs identified the worse is long term survival \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. The pN stages should powerfully forecast the subjective outcome of treated BC patient the end-point of which is either recurrences or deaths. The disease free survival (DFS) and overall survival (OS) of BC should be long in pN0 and shortest in pN3 stages that is number of recurrence or deaths should be lowest in pN0 and highest in pN3 subgroup at a particular time interval. It might be possible that pN staging should anticipate prognosis of the BC patients with precision. The aims of study were to indicate practical clinical outcome of treated BC patients based on pN stages and lymph node ratio (LNR) subgroups. The objectives of this study were to (1) standardize Level 2 OPS by adding ipsilateral ALND and avoid contralateral symmetry surgery, (2) the number of BC patients presented in different pN stages and LNR subgroups, (3) the distribution of number of recurrences and deaths and (4) DFS and OS of different subgroups at a defined follow-up date, and (5) survival functions estimates of pN stages and LNR subgroups after deaths of all patients of any one subgroup. This study should indicate alternative standard of Level 2 OPS and ability to forecast prognosis by pN stages of BC patient.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis prospective cohort study was conducted on 51 consecutive BC patients diagnosed and treated in Ahsania Mission Cancer and General Hospital, Dhaka, Bangladesh. The study period was from August 2016 through December 2019. The patient\u0026rsquo;s information was collected from documents in the hospital registry using a pretested research instrument after obtaining approval from the ethical board of Ahsania Mission Cancer \u0026amp; General Hospital, Plot # 03, Embankment Dive way, Sector-10, Uttara Model Town, Dhaka-1230, Bangladesh and informed consent of the patients. All patients who underwent BC surgery with ALND in afore said institution and maintaining follow-up from the date of enrolment were included in this study and those had distant metastasis at the time of diagnosis were excluded. Modified radical mastectomy of Patey is a nationally recommended routine surgical procedure for BC and all methods were performed in accordance with the national guidelines and regulation.\u003c/p\u003e\u003cp\u003eData of basic sociodemographic, tumor characters, intervention and outcome related variables were collected. Data collected on BC stage according to TNM staging of 8th edition, types of surgical treatment given, pathological tumor (pT) stage (the greatest dimension in centimeter of a single tumor and larger or largest tumor of multifocal / multicentric BC cases), total axillary lymph nodes (ALNs) and +\u0026thinsp;ve ALNs (presence of any BC cell deposit within ALNs) counts, LNR (i.e. ratio of positive to dissected ALNs), pN stages (i.e. pN0, pN1, pN2, and pN3 stage) of TNM staging of BC \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, LNR subgroups, date of diagnosis of BC by fine needle aspiration cytology or histology (start-point of OS), date of surgical treatment of BC (start-point of DFS), date of diagnosis of recurrence (end-point of DFS) and deaths (end-point of OS), DFS and OS in months, site of recurrence (local or metastatic), cause of death (breast cancer specific or other causes). If recurrence or death of patients didn\u0026rsquo;t occurred during study period or they were lost to follow-up at the last known contact was indicated as censored.\u003c/p\u003e\u003cp\u003eData were analyzed according to 2 follow-up dates: (1) last follow-up date of July 22, 2025 for OPS cases and (2) for assessment of BC prognosis on December 2022 because at that follow-up date death of all patients belonging to high-risk LNR subgroup had occurred. Follow-up study should continue further.\u003c/p\u003e\u003cp\u003eMedian and mean age of the patients were 48 and 47.29\u0026thinsp;\u0026plusmn;\u0026thinsp;9.84 (28\u0026ndash;75) years respectively. Female patients were 50 (98%), mean height was 1.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07 (1.4\u0026ndash;1.78) meters. Median and mean weight were 59 and 59.16\u0026thinsp;\u0026plusmn;\u0026thinsp;10.59 (35\u0026ndash;103) kg respectively and mean body mass index was 25.71\u0026thinsp;\u0026plusmn;\u0026thinsp;4.47 (14.2\u0026ndash;40.23) kg/m\u003csup\u003e2\u003c/sup\u003e. This data was published in an earlier report \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe \u0026ndash;ve LN cases were 13 (25.5%) and +\u0026thinsp;ve LN cases 38 (74.5%). Median and mean ALNs dissected were 12 and 13.33\u0026thinsp;\u0026plusmn;\u0026thinsp;5.23 (6\u0026ndash;26) LNs. Number of ALNs removed within range of 6 to 9 was 11 (21.6%), 10 to 15 was 27 (53.1%), 16 to 20 was 7 (13.73%), and 21 to 26 was 6 (11.76%). Median and mean number of +\u0026thinsp;ve LNs were 3 and 4.04\u0026thinsp;\u0026plusmn;\u0026thinsp;4.67 (0\u0026ndash;20) LNs. Median and mean number of +\u0026thinsp;ve LNs in Surgery-First group were 4 and 5.37\u0026thinsp;\u0026plusmn;\u0026thinsp;4.69 (1\u0026ndash;20) LNs and of NAC-Surgery group were 4.33 and 4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.12 (0\u0026ndash;8) LNs respectively. This data was published in another earlier report \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eLNR divided into low (\u0026le;\u0026thinsp;0.2) -, intermediate (0.21\u0026ndash;0.65) - and high-risk (\u0026gt;\u0026thinsp;0.65) subgroups according to cut-off value of a previous published report \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eAll treated BC patients were included. MRM performed in majority of cases. Most cases of ALND is accomplished by Level I and II and in selected cases Level III dissection.\u003c/p\u003e\u003cp\u003eIn Level 2 OPS cases step-2 volume displacement technique of cancer bearing breast done using periareolar two concentric circular incision. The inner circular incision was put outside the nipple-areolar complex and de-epithelialization done in between incisions. Then undermining of skin were attained to release breast tissue to allow adequate mobilization for safe excision of cancer and reshaping of breast. Partial mastectomy done to remove the malignant tumor and a margin of healthy tissue around it resulting in excision of \u0026gt;\u0026thinsp;20% of breast tissue. Redundant breast skin is preserved to provide room for future enlargement of breast and achievement of original size. The remaining adequately mobilized breast tissue were repositioned to fill-up the cavity created by tumor excision. The cavity is marked with vascular clips around the wall. Thus a new smaller breast is created with almost natural shape along with some improvement of degrees of ptosis. Ipsilateral ALND done through a separate small incision at the upper end of anterior axillary fold for lymphedema effect on reconstructed breast, pN staging, and LNR sub-grouping. In all 3 OPS cases reduction mammoplasty of opposite normal breasts were avoided. All other adjuvant therapy offered according to highly individualized protocol of BC treatment.\u003c/p\u003e\u003cp\u003eThe sliced mastectomy specimen and axillary soft tissue were fixed in 10% neutral buffered formalin maintaining and recording cold ischemic time. The specimen send to pathology laboratory where grossing of the specimen was performed by the pathologist according to set protocol. Tissue blocks taken were (1) four blocks from breast tumor, (2) one each from skin and nipple and (3) of any multifocal/multicentric tumor, (4) one or two from non-tumorous area of breast, (5) one each from deep and peripheral resection margins, (6) two from each \u0026gt;\u0026thinsp;2 cm ALNs and (7) one from each of other resected LNs. The blocks were processed for routine paraffin embedding. Sections were cut at 5\u0026micro; thickness and stained with routine H and E staining methods. After mounting in a slide were examined microscopically by pathologist. Immunohistochemistry performed on tumor tissue and a combined reports provided.\u003c/p\u003e\u003cp\u003eStatistical analysis was performed using SPSS version 23 (IBM Corp, USA). Mean was expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (minimum-maximum). Median values were recorded when possible to provide an accurate picture of distributions. Student\u0026rsquo;s t-test was used for continuous and chi-square test for categorical variables, ANOVA, Kaplan-Meier survivability estimate with log-rank test, and univariate and multivariate analysis of Cox regression model of fit done to assess survival outcomes and to identify significance. P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 with 95% confidence interval (CI) were considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOut of three nipple-areola-breast skin sparing OPS plus ipsilateral ALND two (4%) patients were alive till last follow-up on June 2025 and one (2%) patient died on November 2020. Both survivors were pre-menopausal woman one is overweight and other of healthy weight. The operation included complete oncologic resection and partial mastectomy, ipsilateral reconstruction using volume displacement technique through circumareolar double Doughnut incision without removal of redundant skin of breast and contralateral symmetry surgery. Ipsilateral ALND done as an additional procedure. The tumors were pT1 stage, hormone receptors positive, and Her 2 negative. Both patients received adjuvant chemo-, radiation- and antihormone-therapy. Their mean disease free survival were approximately 6 years according to last follow-up date.\u003c/p\u003e\n\u003cp\u003eThe dead postmenopausal woman of OPS was 45 years old had single tumor of 3 cm size involving right breasts of infiltrating ductal carcinoma grade II, \u0026gt;\u0026thinsp;25% breast tissue along with tumor was removed using Level 2 displacement OPS preserving extra skin-nipple-areola of breast and ipsilateral ALND, however, did not received required adjuvant chemo-, radiation-, antihormone-, or targeted-therapy. She had 22 axillary lymph nodes and 4 were positive, progesterone receptor and Her 2 positive, and disease free and overall survival were 15.4 and 19.7 months respectively. The operated breast was free of recurrence, and death was due to widespread bilateral pulmonary and hepatic metastasis.\u003c/p\u003e\n\u003cp\u003eAll three OPS cases achieved enlargement of operated breasts leading to spontaneous symmetrisation (Figs. 1 and 2).\u003c/p\u003e\n\u003cp\u003eThe number of cases belonged to pN0, pN1, pN2, and pN3 were 13 (25.5%), 16 (31.4%), 18 (35.3%), and 4 (7.8%) and of low-, intermediate-, and high-risk LNR were 23 (45.1%), 19 (37.3%), and 9 (17.6%) respectively (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). The difference was highly significant between pN stages and LNR subgroups (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000001\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eThe median and mean duration of follow-up (according to December 2022) were 55.30 and 53.04\u0026thinsp;\u0026plusmn;\u0026thinsp;15.66 (15.60-81.23), of DFS 51.11 and 47.58\u0026thinsp;\u0026plusmn;\u0026thinsp;16.70 (13.6-73.63), and of OS 52.43 and 50.95\u0026thinsp;\u0026plusmn;\u0026thinsp;14.69 (15.57\u0026ndash;74.80) months respectively. Total number of recurrences were 17 (33.3%) and 34 (66.7%) were censored of them 6 (17.65%) cases were dropped out (censored unrelated to the study during follow-up period). Number of deaths were 21 (41.18%).\u003c/p\u003e\n\u003cp\u003eThe distribution of recurrences of pN0, pN1, pN2, and pN3 of total were 2 (3.9%), 5 (9.8%), 9 (17.6%) and 1 (2%) cases respectively with no significant difference (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e232\u003c/em\u003e). The number of recurrences of low-, intermediate-, and high-risk LNR of total were 6 (11.8%), 5 (9.8%), and 6 (11.8%) respectively (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) with no significant difference (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e065\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003eTotal number of deaths were 21(41.20%). The median and mean duration of DFS of death cases were 39.60 and 35.44\u0026thinsp;\u0026plusmn;\u0026thinsp;17.63 (1.3\u0026ndash;59.50) and of OS were 46.12 and 44.02\u0026thinsp;\u0026plusmn;\u0026thinsp;17.80 (15.57\u0026ndash;74.80) months respectively. The distribution of deaths among pN0, pN1, pN2, and pN3 out of total were 3 (5.9%), 5 (9.8%), 10 (19.6%), and 3 (5.9%) respectively with no significant difference (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.12\u003c/em\u003e). The death distribution among low-, intermediate- and high-risk LNR were 6 (25%), 5 (26.32%), and 9 (100%) respectively (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e) with significant difference (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.000393\u003c/em\u003e). Distribution of deaths among pN and LNR subgroups was significant (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e013\u003c/em\u003e).\u003c/p\u003e\n\u003cdiv\u003eThe estimate mean survival time of DFS for pN0, pN1, pN2, and pN3 were 59.4 (CI 55.7 and 63.2), 59.6 (CI 47.8 and 71.4), 48.5 (CI 36.6 and 60.3), and 46.7 (CI 39.6 and 53.0) months respectively. Estimated median survival time of DFS for pN2 was 50.4 (CI 34.7 and 66.2) months. Pair wise comparisons (Log Rank test) of DFS for pN stages indicated no significant difference between pN0, pN1 and pN3 except between pN0 and pN2 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e048\u003c/em\u003e). However, survival functions curve of DFS for pN0 indicated best possible survival time while curves of pN1, pN2 and pN3 were similar and indicated worst survival time (Fig.\u0026nbsp;3).\u003c/div\u003e\n\u003cp\u003eThe estimate mean survival time of DFS for low-, intermediate-, and high-risk LNR were 58.6 (CI 52.8 and 64.3), 63.8 (CI 54.6 and 73.1), and 23 (CI 14.1 and 31.9) months respectively. The estimate median survival time of high-risk LNR was 16.2 (CI 8.8 and 23.6) months. Pair wise comparison (Log Rank) indicated highly significant difference between low- and intermediate- risk (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.003\u003c/em\u003e), low- and high-risk (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000003\u003c/em\u003e) and intermediate- and high-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.000115\u003c/em\u003e). The curves of low- and intermediate-risk LNR were similar with best, and high-risk LNR with worst survival time (Fig.\u0026nbsp;4).\u003c/p\u003e\n\u003cp\u003eThe estimate mean survival time for OS of pN0, pN1, pN2 and pN3 subgroups were 62.61 (95% CI were 57.89 and 67.34), 66.61 (95% CI 59.14 and 74.08), 52.77 (95% CI 43.73 and 61.81), and 53.18 (95% CI 26.08 and 80.28) months respectively. The estimate median survival time for OS of pN2 and pN3 were 62.13 (95% CI 45.35 and 78.91) and 40.73 (95% CI 6.48 and 74.98) months respectively. Overall comparison (Log Rank test) of survival function indicated no significant difference of OS of pN stages (Log rank test, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e068\u003c/em\u003e). Pair wise comparisons indicated significant difference between pN0 and pN2 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e048\u003c/em\u003e) for OS and no significant difference were observed among pN0 and pN1 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e891\u003c/em\u003e), pN0 and pN3 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e10\u003c/em\u003e), pN1 and pN2 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e058\u003c/em\u003e), pN1and pN3 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e139\u003c/em\u003e), and pN2 and pN3 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e863)\u003c/em\u003e. The survival function estimator of OS indicated curves of pN0 and pN1 were similar and the best survival time. On the other hand curves of pN2 and pN3 had similar but the worst survival time (Fig.\u0026nbsp;5).\u003c/p\u003e\n\u003cp\u003eThe estimate mean survival time of OS for LNR of low-, intermediate-, and high-risk LNR were 68.21 (95% CI 60.97 and 75.93), 68.50 (95% CI 62.08 and 74.93), and 37.35 (95% CI 23.54 and 51.15) months respectively. The estimate median survival of low- and high-risk LNR were72.63 (95% CI 5.75 and 89.51) and 27.7 (95% CI 12.13 and 43.27) months respectively. Overall comparisons (Log Ran test) of survival functions of OS of LNR group indicated highly significant difference (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.000006\u003c/em\u003e). Pair wise comparisons of OS indicated significant difference between low- and high-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000041\u003c/em\u003e), and intermediate- and high-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000161\u003c/em\u003e). There was no significant difference between low- and intermediate-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e819\u003c/em\u003e). The survival function estimator plots for OS indicated curves of low- and intermediate-risk LNR were similar with the best possible survival time. On the other hand curve of high-risk LNR indicated the worst survival time (Fig.\u0026nbsp;6).\u003c/p\u003e\n\u003cp\u003eThe variables like age in years, menopausal age groups, body weight, BMI, BMI categories, number of multicentric/multifocal breast tumor, maximum diameter of the tumor, pT stages, total number of ALNs dissected, number of positive ALN, histological grade, pN stages, LNR, LNR subgroups, ER, PR and Her-2 receptor, TNM stage group, and NAC status were analyzed using Cox regression model of fit. The univariate analysis of aforesaid covariates of DFS of BC of pN stages with statistical significance were of BMI categories (\u0026szlig; = 0.693, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e039\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;1.99, CI of HR 1.036 and 3.859),LNR (\u0026szlig; = 2.408, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e003\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;11.109, CI of HR 2.286 and 53.995), LNR subgroups (\u0026szlig; = 1.221, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e003\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;3.391, CI 1.531 and 7.51), Her-2 positive BC (\u0026szlig; = 2.085, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000264\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;8047, CI 2.625 and 24.69), and NAC status (\u0026szlig; = 1.453, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e005\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;4.276, CI for HR 1.564 and 11.691). However, variables like age, pre- and post-menopausal age group, body weight, BMI, number of tumor in the breast, maximum diameter of the tumor, total ALN and positive ALN counts, pN stage, histological grade, ER and PR positivity, and TNM stage grouping were not significant. The multivariate Cox regression analysis of covariates for DFS were BMI categories, LNR and LNR subgroups indicated statistical significant goodness of fit of the variables in the model [ꭓ\u003csup\u003e2\u003c/sup\u003e(6)\u0026thinsp;=\u0026thinsp;22.8, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.001] and independent predictor variables were found to be Low-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e012\u003c/em\u003e), Intermediate-risk LNR (\u0026szlig; = -5.434, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e044\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;0.004, CI 0.000022 and 0.873), and High-risk LNR (\u0026szlig; = -4.861, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e008\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;0.008, CI 0.00021 and 0.286). Univariate analysis of Cox regression model of fit for covariates of OS of BC with statistical significance were pT stages (\u0026szlig; = 0.798, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e03\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;2.222, CI of HR 1.08 and 4.569), number of positive LNs (\u0026szlig; = 0.077, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e022\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;1.08, CI of HR 1.011 and 1.154), pN stages (\u0026szlig; = 0.491, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e044\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;1.634, CI 1.013 and 2.636), LNR (\u0026szlig; = 2.048, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e001\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;7.751, CI 2.238 and 26.837), LNR subgroups (\u0026szlig; = 1.071, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e001\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;2.02, CI 1.533 and 5.56), Her 2 positive BC (\u0026szlig; = 2.075, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000073\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;7.965, CI of HR 2.856 and 22.209), TNM stage grouping (\u0026szlig; = 0.239, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e036\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;1.269, CI 1.015 and 1.587) and NAC status (\u0026szlig;= 1.188, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e012\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;3.280, CI 1.298 and 8.289). The variables like age in years, pre- and post-menopausal age group, body weight, BMI, number of tumor in the breast, maximum diameter of tumor, histological grade, dissected ALN counts, ER and PR positivity were not statistically significant as covariates of OS of BC. Model coefficients of multivariate analysis of Cox regression survival model of OS of pT stages, number of positive ALNs, pN stages, LNR, LNR subgroups, and TNM stage grouping indicated significant goodness of fit when the model included this variables [ꭓ\u003csup\u003e\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e (16)\u0026thinsp;=\u0026thinsp;41.741, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000431\u003c/em\u003e] and independent covariates were Low-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e007\u003c/em\u003e), Intermediate-risk LNR (\u0026szlig; = -9.468, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e019\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;0.000077, CI 0.000 and 0.213), and High-risk LNR (\u0026szlig; = -9.009, \u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e005\u003c/em\u003e, HR\u0026thinsp;=\u0026thinsp;0.000122, CI 0.000 and 0.07).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eNowadays Level 2 OPS is most frequent surgical modality of treatment of BC \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e which is a combination of excision of the malignant breast tissue with at least 0.5 mm margin of surrounding healthy tissue and plastic surgery techniques for immediate reconstruction and symmetry surgery performed by reduction mammoplasty of opposite normal breast. On the other hand every surgical oncologist aware of the lymphedema of the upper extremity and pectoral region including leftover breast as a complication of ALND. Thus we can easily utilize the breast lymphedema of ALND as an alternative mechanism of spontaneous enlargement of the operated cancer-bearing reconstructed small breast instead of reduction of size of opposite normal breast. It should be expected that easier ipsilateral ALND compared to popular reduction mammoplasty of contralateral normal breast should be attractive routine alternative in OPS \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e because of skin sparing OPS with ipsilateral ALND developed a good looking scar free enlargement of operated cancer bearing breasts, create a more natural looking breast mound, maintain intact sensation and capability of lactation in every individual cases, and improvement of patient\u0026rsquo;s self-esteem and body image.\u003c/p\u003e\u003cp\u003eThis study observed significantly sizeable number of high risk cases were included in high-risk LNR subgroup compared to that of pN3 stage (\u003cem\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/em\u003e) of BC patients. LNR is a better predictor of prognosis than pN stage was observed in other study \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. Overall comparisons of DFS indicated no \u003cem\u003esignificant\u003c/em\u003e difference of survival functions (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.074\u003c/em\u003e) in pN stages and highly significant difference in LNR subgroups (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.000006\u003c/em\u003e). Pair wise comparison of survival functions of DFS of pN subgroups indicated significant difference of pN0 with pN3 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.006\u003c/em\u003e) and with pN2 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.018\u003c/em\u003e), and survival plots of DFS indicated similar curves of pN1, pN2, and pN3 with no statistically significant difference between them. Thus pN0 of pN stage can well assess good prognosis with long survivability and on the other hand pN1, pN2 and pN3 made vague assessment of worst prognosis. The overall comparisons of survival functions of DFS of LNR indicated better expression with high precision of survival time (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000066\u003c/em\u003e) than pN staging (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e068\u003c/em\u003e). Pair wise comparisons indicated highly significant difference of survival functions of DFS was observed between low- and high-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000001\u003c/em\u003e), and intermediate- and high-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000161\u003c/em\u003e) and no significant difference between low- and intermediate-risk LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e772\u003c/em\u003e) indicated very high precision of DFS. The survival plots of low- and intermediate-risk LNR of DFS curves are similar indicating better and that of high-risk LNR worst survivability. The better predictive power of LNR than pN stages of DFS of BC patients was observed in a retrospective study \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOverall comparison of survival functions of OS of pN stage indicated no significant difference (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e068\u003c/em\u003e) and that of OS of LNR group significant difference (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000006\u003c/em\u003e). Pair wise comparisons of survival function of OS of pN stage indicated significant difference between pN0 and pN2 (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e048\u003c/em\u003e), and no significant differences between pN0 with pN1and pN3, as well as pN1 with pN2 and pN3. The curves of the survival plot of pN1, pN2, and pN3 were similar indicating pN staging discriminate vague prognosis thus counting positive axillary lymph node only is not enough for prognostication. On the other hand, no significant difference of survival function of OS was observed between low- and intermediate-risk LNR subgroups (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e819\u003c/em\u003e) and their curves in the survival plot were similar too indicating best and high risk LNR subgroup had worst survival time. Pair wise comparisons of OS indicated significant difference between low- and high-risk LNR subgroups (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000041\u003c/em\u003e), and that of intermediate- and high-risk LNR subgroups (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000161\u003c/em\u003e). High-risk LNR subgroup had worst survival time. It is indicated that prognostication of BC using LNR could be possible with precision fulfilling mandatory requirement of ALND. One retrospective study of OS indicated LNR is superior to pN stage for the determination of BC prognosis \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e and another meta-analysis indicated high LNR value is associated with short OS of BC patients after neoadjuvant chemotherapy \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. The reality is with the increased rate of detection of early BC (T1, T2) after introduction of screening program (40% T1 and 30% T2) \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003eresulting in improvement of breast cancer-associated mortality \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003eand increased procedures of sentinel lymph node biopsy (SLNB) along with declined number of ALND because of node staging of TNM classification require positive LN counts only. One study in China indicated the use of ALND declined from 94% on 1998 to 36% on 2004 in breast cancer surgery \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. Another study in Spain indicated rate of ALND was 91% in 1998 that decreased to 34% within 2017 \u003csup\u003e19\u003c/sup\u003e. There is progressively increased rate of detection of number of positive lymph nodes after introduction of SLNB due to significantly increased detection of micrometastasis form through pathological examination. Currently surgical oncologists of breasts cherishing the idea that ALND should be a selective operation. On the other hand, gastrointestinal (GI) oncologist give importance to extensive systemic LN dissection for carcinoma of the esophagus, stomach and colon. An analysis of Surveillance, Epidemiology, and End Results database showed that calculated OS increased by 7.6% for T1/2N0, 11% for T3N0, and 7% for T3N1 for every additional 10 LNs dissected which could be up to a cut point at 40 dissected LNs and data provided support in favor of extended lymphadenectomy for superior survival \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Comprehensive lymphadenectomy is a routine procedure in cases of GI carcinomata. Thus axillary lymphadenectomy should be a routine procedure irrespective of nodal status because of BC is an adenocarcinoma.\u003c/p\u003e\u003cp\u003eThis small scale prospective study indicated some important observations deserving large scale research. There is no national breast screening program in this country.\u003c/p\u003e\u003cp\u003ePair wise comparisons of survival functions indicated no significant difference between low- and intermediate-risk LNR in DFS (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.772\u003c/em\u003e) and OS (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.819\u003c/em\u003e). Survival functions estimator curves of DFS and OS also indicated low- and intermediate-risk LNR were similar although current study credited to three LNR risk groupings \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Above findings indicated that intermediate-risk should be incorporated in the low-risk LNR subgroup and LNR should be classified into low- and high-risk. Low- and high-risk LNR subgrouping was also adapted in other study \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe overall Cox regression model of fit for DFS indicated statistically significant (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.001\u003c/em\u003e) improvement of the model after addition of following covariates and efficiently explained the data. Negative regression coefficient (\u0026szlig;) of the variables like age in year (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e02\u003c/em\u003e) and the number of positive pN (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e039\u003c/em\u003e) were observed statistically significant indicating that these covariates improved prognosis with their increments. One study indicated younger BC age group exhibit more aggressive disease than older patient \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e and higher number of positive LNs were associated with shorter DFS \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. Positive \u0026szlig; were observed in post-menopausal age group, BMI, tumor diameter, number of dissected LNs, LNR, TNM stage grouping, and NAC status. Statistically significant increase of recurrences of BC or decreased DFS of postmenopausal women (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e025\u003c/em\u003e) was observed in his study indicated an association with the number. Similar result was observed in other study \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. Statistically significant positive \u0026szlig; of BMI (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e024\u003c/em\u003e) of this study indicated obese patients experienced worst DFS and was similar to that of other observations \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. With the increase of pT stage (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e007\u003c/em\u003e) there was increased hazard rate, increased recurrence and decreased DFS. Similar result was observed in other study \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. Regression coefficient (\u0026szlig;) of histological grade was slightly positive indicating that increased histological grade there was slight increase of recurrence rate. However, the effect was minimal. LNR subgroups significantly fit in the model (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e002\u003c/em\u003e) and indicated longer DFS in low-risk LNR than high-risk LNR. Similar result was observed in other study \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. All NAC treated BC patients of this study had partial pathological response and indicated statistically significant decreased DFS (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e0000183\u003c/em\u003e) compared to the patients who did not received NAC. Similar result was also observed in other study\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Intermediate- (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.044\u003c/em\u003e) and high- risk (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.008\u003c/em\u003e) LNR were observed as independent covariates like that of other study \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe overall Cox regression model of fit for OS indicated statistically significant (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e000038\u003c/em\u003e) improvement of the model after inclusion of following defined covariates and efficiently explained the data. Slightly negative regression coefficient was observed for age in year, indicating that lower age is associated with higher hazard rate of OS, however, the effect is not statistically significant. Similar result was observed in another study \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. Statistically significant negative \u0026szlig; was observed with Her 2 positive status (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0.000073\u003c/em\u003e) indicating association with decreased hazard rate thus increased OS. Similar result observed in other study \u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. Statistically significant positive regression coefficient were observed with LNR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e001\u003c/em\u003e), indicating that as LNR increased hazard rate increased significantly and OS decreased. Similar result observed in other study \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Positive regression coefficient of number of patients receiving NAC was significant (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e012\u003c/em\u003e) indicated that increased number of events (deaths) were associated with increased number of NAC patients compared to those not receiving NAC. Similar result observed in other study \u003csup\u003e31\u003c/sup\u003e. Positive regression coefficient with no statistical significance were observed with age group (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e0264\u003c/em\u003e), body weight (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e11\u003c/em\u003e), BMI (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e062\u003c/em\u003e), number of breast tumors (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e798\u003c/em\u003e), maximum diameter of the tumor (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e263\u003c/em\u003e), histological grade (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e387\u003c/em\u003e), total number of dissected LNs (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e335\u003c/em\u003e), ER (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e317\u003c/em\u003e), and PR (\u003cem\u003ep\u0026thinsp;=\u0026thinsp;0\u003c/em\u003e.\u003cem\u003e551\u003c/em\u003e). The multivariate Cox regression model analysis indicated that low-risk LNR was associated with increased DFS and OS. On the other hand intermediate- and high- risk LNRs were associated with decreased DFS and OS indicating ALND forecasts prognosis of breast cancer with precision. Similar result was observed in other study \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIpsilateral axillary lymph node dissection should diminishes workload of Level 2 step 3 of contralateral symmetry surgery of normal breasts of oncoplastic surgery, involvement of plastic surgeons, and spares extra time of training program on account of simplicity. It decreases chances of post-operative complications like infection, scar formation and deformity of the contralateral normal breast. Long term follow-up report indicated promising result of this alternative procedure, however, sample size is very small. Those who are experts in minimally invasive surgery on breast cancer should come forward to re-evaluate endoscopic application of this alternative model for further improved standardization.\u003c/p\u003e\u003cp\u003eGreater number of high-risk breast cancer cases were brought to light due to routine axillary dissection and calculation of lymph node ratio subgrouping, and found be a unique procedure to identify the best and worst prognosis with efficient discrimination. Study also observed that pathological node staging of TNM classification is a powerless predictor of prognosis of breast cancers. Axillary lymph node dissection for breast cancers is a unique independent predictor could sensibly discriminate good prognosis from bad and worst one with distinct precision. Consequently lymph node ratio should be incorporated as superscript of pathological node stages of TNM classification for breast cancer mentioning positive and total number of dissected lymph nodes. The counting of only positive axillary lymph nodes is insufficient to predict prognosis of breast cancer.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAJCC: American joint committee on cancer\u003c/p\u003e\n\u003cp\u003eALND: Axillary lymph node dissection\u003c/p\u003e\n\u003cp\u003eALNs: Axillary lymph nodes\u003c/p\u003e\n\u003cp\u003eANOVA: Analysis of variance\u003c/p\u003e\n\u003cp\u003eBC: Breast cancer\u003c/p\u003e\n\u003cp\u003e\u0026szlig;: Regression coefficient for the variable\u003c/p\u003e\n\u003cp\u003eCI: 95% confidence interval\u003c/p\u003e\n\u003cp\u003eDFS: Disease free survival\u003c/p\u003e\n\u003cp\u003eER: Estrogen receptor\u003c/p\u003e\n\u003cp\u003eFISH: Fluorescence in situ hybridization\u003c/p\u003e\n\u003cp\u003eGI: Gastrointestinal\u003c/p\u003e\n\u003cp\u003eHer2: Human epidermal growth factor receptor\u003c/p\u003e\n\u003cp\u003eHR: Hazard ratio\u003c/p\u003e\n\u003cp\u003eIBM: International Business Machine Corporation\u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLNs: Lymph nodes\u003c/p\u003e\n\u003cp\u003eLNR: Lymph node Ratio\u003c/p\u003e\n\u003cp\u003eMRM: Modified radical mastectomy\u003c/p\u003e\n\u003cp\u003eNAC: Neoadjuvant chemotherapy\u003c/p\u003e\n\u003cp\u003eOPS: Oncoplastic surgery\u003c/p\u003e\n\u003cp\u003eOS: Overall survival\u003c/p\u003e\n\u003cp\u003epN: Pathological node\u003c/p\u003e\n\u003cp\u003ePR: Progesterone receptor\u003c/p\u003e\n\u003cp\u003eSLNB: Sentinel lymph node biopsy\u003c/p\u003e\n\u003cp\u003eSPSS: Statistical package for the social sciences\u003c/p\u003e\n\u003cp\u003eTNM: Tumor, lymph Node, Metastasis\u003c/p\u003e\n\u003cp\u003eUICC: International union against cancer\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eresearch work was conducted\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eafter obtaining approval from the institutional ethical board and informed consent of the patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent of publication:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors consented for publication of this manuscript in the Breast Cancer Research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of supporting data:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective research work is continuing its\u0026rsquo; long-term follow-up study. The dataset used during current study are available from corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interest.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no financial arrangement with anyone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. K. Mostaque contributed to the design of the experiment, performed all surgical interventions, collection of data of the patients, analysis and interpretation of data, continuing long term follow-up, and preparation of the paper. M. Kamal contributed designing pathological methodology, perform most of the histology and immunohistochemistry of the specimens and revising the manuscript. A.M.M. Shariful Alam contributed in collection of data, designing methodology, and repeated revision of manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge with sorrow the recent death of the author Professor Dr. M. Kamal due to liver cancer who contributed so much in designing pathological methodology, in preparation of histology and immunohistochemistry reports and revision of manuscript. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFreeman MD, Gopman JM, Salzberg CA. The evolution of mastectomy surgical technique: from mutilation to medicine. Gland Surg. 2018 [Accessed 1 January 2023];7(3):308 \u0026ndash; 315. DOI:10.21037/gs.2017.09.07\u003c/li\u003e\n\u003cli\u003eGiuliano AE, Ballman KV, McCall L, Beitsch PD, Brennan MB, Kelemen PR, et al. Effect of axillary dissection vs no axillary dissection on 10-years overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017 [Accessed 9 April 2023];318(10):918-926. DOI: 10.1001/jama.2017.11470\u003c/li\u003e\n\u003cli\u003eMostaque AK, Mamun MAA, Kamal M, Alam AMMS, Chowdhury IU. Oncoplastic surgery and outcome prediction deserve axillary lymph node dissection \u0026ndash; treatment results of 51 cases of breast cancer. IISJ. 2021 [Accessed 11 June 2023];5(09):25-37. Available from https://iisj.in/index.php/iisj/article/view/344\u003c/li\u003e\n\u003cli\u003eArnone P, Zurrida S, Viale G, Dellapasqua S, Montagna E, Arnaboldi P, et al. The TNM classification of breast cancer: need for change. Update Surg. 2010 [Accessed 31 January 2023];26:75 \u0026ndash; 81. DOI: 10.1007/s13304-010-0014-y\u003c/li\u003e\n\u003cli\u003eSawaki M, Shien T, Iwata H. TNM classification of malignant tumors (Breast cancer study group). JJCO. 2019 [Accessed 29 January 2023];49 (3):228 -231. DOI: 10.1093/jjco/hyy182\u003c/li\u003e\n\u003cli\u003eXiao XS, Tang HL, Xie XH, Li LS, Kong YN, Wu MQ, et al. Metastatic axillary lymph node ratio (LNR) is prognostically superior to pN staging in patients with breast cancer \u0026ndash; results for 804 Chinese patients from a single institution. Asian Pac J Cancer Prev. 2013;14(9):5210\u0026ndash;5223. DOI: https://dx.doi.org/10.7314/APJCP.2013.14.9.5219\u003c/li\u003e\n\u003cli\u003eChang JM, Leung JWT, Moy L, Ha SA, Moon WK. Axillary nodal evaluation in breast cancer: state of the art. J Radiol. 2020 [Accessed 24 January 2023];295(3):500 \u0026ndash; 515. https://doi.org/10.1148/radiol.2020192534\u003c/li\u003e\n\u003cli\u003eSafavi A, Kaviani A, Mohammadzadeh N, Zand S, Krag DN. Breast cancer prognostication by pathologic node staging (pN-staging) system versus lymph node ratio (LNR): A critical review of conflicts with number of nodes, Z-0011 trial, staging cut- points, neo-adjuvant therapy and survival estimation. Arch Breast Cancer. 2017;4(4):110-123. DOI: 10.19187/abc.201744110-123\u003c/li\u003e\n\u003cli\u003eZhao X, Wei J, Li X, Tang H, Wang P, Cao S. Increasing negative lymph node count predicts favorable OS and DFS in breast cancer with different lymph node-positive subgroups. J PloS ONE. 2018;13(3):e0193784. DOI: https://doi.org/10.1371/journal.pone.0193784\u003c/li\u003e\n\u003cli\u003eKoh J, Kim MJ. Introduction of a new staging system of breast cancer for radiologists: An emphasis on the prognostic stage. Korean J Radiol. 2019 [Accessed 7 May 2023];20(1):69-82. DOI: 10.3348/kjr.2018.023\u003c/li\u003e\n\u003cli\u003eMostaque AK, Mamun MAA, Alam AMMS, Chowdhury IU, Sharif RB. Assessment of anthropometric measurements, time lag between diagnosis and surgery, postoperative recovery time, and outcome of oncoplastic surgery of treated breast cancer patients. J MAR Oncol. 2022 [Accessed 13 Oct 2023];3(2):1-17. Available from: htpps://www. medicalandresearch.com\u003c/li\u003e\n\u003cli\u003eThompson PW, Chatterge A, Losken A. Standards in oncoplastic breast-conserving surgery. Ann Breast Surg. 2022 [Accessed 9 September 2024];6:37. DOI: 10.21037/abs-21-33\u003c/li\u003e\n\u003cli\u003eAhn SH, Kim HJ, Lee JW, Noh DY, Yang JH, Jung SS, et al. Breast Cancer Res Treat. 2011 [Accessed 14 January 2024];130:507-515. DOI: https://doi.org/10.1007/s10549-011-1730-9\u003c/li\u003e\n\u003cli\u003eWu S-G, He Z-Y, Li Q, Lin H-X, Guan X-X. Prognostic value of metastatic axillary lymph node ratio for Chinese breast cancer patients. J PloS ONE. 2013 [Accessed 12 June 2024];8(4):e61410. DOI: 10.1371/journal.pone.0061410\u003c/li\u003e\n\u003cli\u003eLiu J, Li Y, Zhang W, Yang C, Yang C, Chen L, et al. The prognostic role of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy: a doe response meta-analysis. Front Surg. 2022 [Accessed 12 June 2024];9:971030. DOI: 10.3389/fsurg.2022.971030\u003c/li\u003e\n\u003cli\u003eEisemann N, Waldmann A, Kataliic A. Epidemiology of breast cancer \u0026ndash; current figures and trend. Gaburtsilfe Feauenheilkd. 2013 [Accessed 22 December 2023];73(2):130-135. DOI: 10.1055/s-0032-1328075\u003c/li\u003e\n\u003cli\u003eTriev PDY, Mello-Thomas CR, Baron ML, Lewis SJ. Look how far we have come: BREAST cancer detection education on the international stage. Front Oncol. 2023 [Accessed 23 December 2023);12:1023714. DOI: 10.3389/onc.2022.1023714\u003c/li\u003e\n\u003cli\u003eGou Z, Lu X, He M, Yu L. Trends in axillary surgery and clinical outcomes among breast cancer patients with sentinel node metastasis. The Breast. 2022 [Accessed 20 December 2023];63:9-15. DOI: 10.1016/j.breast.2022.02.014\u003c/li\u003e\n\u003cli\u003eGarcia-Novoa A, Acea-Nebril B, Casal-Beloy I, Garea CC, Gomez-Dovigo A, Builes-Ramirez S, et al. The decline of axillary lymph node dissection in breast cancer. Evolution of its indication over the last 20 years. J CIR ESP. 2019 [Accessed 24 December 2023];97(4):222-229). DOI: 10.1016/j.cir.eng,2019,01.018\u003c/li\u003e\n\u003cli\u003eSmith DD, Schwarz RR, Schwarz RE. Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database. J Clin Oncol. 2005 [Accessed 26 December 2023];23(28):7114-24. DOI: 10.1200/jco.2005.14.621\u003c/li\u003e\n\u003cli\u003eSoran A, Ozman T, Salamat A, Soybir G, Johnson R. Lymph node ratio (LNR): Predicting prognosis after neoadjuvant chemotherapy (NAC) in breast cancer patients. Eur J Breast Health. 2019 [Accessed 12 August 2024];15(4):249-255. DOI: 10.5152/ejbh.2019.4848\u003c/li\u003e\n\u003cli\u003eChen H-I, Zhou M-q, Tian W, Meng K-x, He H-f. Effect of age on breast cancer patient prognosis: A population-based study using the SEER 18 data base. PloS ONE. 2016 [Accessed 9 ay 2025];11(10):e0165409. doi: 10.1371/journal.pone.0165409\u003c/li\u003e\n\u003cli\u003eTonellotto F, Bergman A, de Souza Abrah\u0026aacute;o K, de Aguiar SS, Bello MA, Thuler LCS. Impact of number of positive lymph nodes and lymph node ratio on survival of women with node positive breast cancer. Eur J Breast Health. 2019 [Accessed 14 ay 2025];15(2):76 \u0026ndash; 84. doi: 10.5152/ejbh.2019.4414\u003c/li\u003e\n\u003cli\u003eXie Y, Deng Y, Wei S, Huang Z, Li L, Huang K et al. Age has a U-shaped relationship with breast cancer outcomes in women: a cohort study. Front Oncol.2023 [Accessed 15 May 2025];13:1265304. doi: 10.3389/fonc.2023.1265304\u003c/li\u003e\n\u003cli\u003eZangouri V, Balaneji SS, Golmoradi R, Kafili E, Bologhi S, Mousavi SA et al. Effects of BMI on prognosis, disease-free survival and overall survival of breast cancer. BC Cancer. 2025 [Accessed 16 May 2025];25:257. doi: https://doi.org/10.1186/s12885-025-13638-7\u003c/li\u003e\n\u003cli\u003eLiu Y, He , Zuo W-J, Hao S, Wang Z-H, Shao Z-M. Tumor size still impacts prognosis in breast cancer with extensive nodal involvement. Front Oncol. 2021 [Accessed 16 May 2025];11:585613. doi: 10.3389/fonc.2021.585613\u003c/li\u003e\n\u003cli\u003eSolac M, Turkoz FP, Keskin O, Aksoy S, Babacan T, Sarici F e al. The Lymph node ratio as an independent prognostic factor for non-metastatic node-positive breast cancer recurrence and mortality. JBUON. 2015 [Accessed 19 May 2025];20(3):737-745. PMID: 26214625\u003c/li\u003e\n\u003cli\u003eGentile D, Sagona A, Camillia CD, Fernandes B, Barbieri E, Grimaldi SD et al. Pathologic response and residual tumor cellularity after neo-adjuvant chemotherapy predict prognosis in breast cancer patients. J Breast.2023 [Accessed 20 May 2025];69:323-329. doi: htpps://doi.org/10.1016/j.breast.2023.03.016\u003c/li\u003e\n\u003cli\u003eSbaity E, Tamim H, Fuleihan G E-H, Abbas J, Zahwe M, Sayed RE et al. Effect of young age (below 40 years) on oncologic outcomes in Lebanese patient with breast cancer: a matched cohort study. BMC Cancer. 2024 [Accessed 25 May 2025];24:560. doi: https://doi.org/10.1186/s12885-024-11910-w\u003c/li\u003e\n\u003cli\u003eL\u0026ouml;b S, Linsmeier E, Herbert SL, Schlai\u0026szlig; T, Kiesel , Wischhusen J et al.Prognostic effect of Her2 evolution from primary breast cancer to breast cancer metastases. J Cancer Res Clin Oncol. 2023 [Accessed 26 May 2025];149(8):5417-5428. doi: 10.1007/s99432-922-94486-0\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1 is 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":"[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":"Oncoplastic surgery axillary dissection model, Breast cancer predictor axillary node staging, Lymph node ratio breast cancer predictor, Independent breast cancer survival predictor","lastPublishedDoi":"10.21203/rs.3.rs-7316406/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7316406/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e After introduction of the radiotherapy in breast cancer multimodality treatment has disregarded the therapeutic value of axillary lymph node dissection (ALND). Common practice is sentinel lymph node biopsy to count positive nodes only to forecast breast cancer prognosis. Exclusion of symmetry surgery, skin sparing breast reconstruction after oncologic resection of cancer, and addition of ipsilateral ALND might induce spontaneous enlargement of reconstructed smaller breast due to lymphedema effect thus help standardization of technical and safety aspects of Level 2 oncoplastic surgery (OPS). The objectives of study were (1) to observe the outcome after inclusion of \u003cem\u003eipsilateral ALND\u003c/em\u003e \u003cem\u003ein place of symmetry surgery of contralateral normal breast in level 2 OPS\u003c/em\u003e and (2) to observe power of assessment of prognosis of pathological node stages and ALND based lymph node ratio (LNR) subgroups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eStudy conducted on 51 surgically treated breast cancer patients of a single institution. Data were collected and analyzed of three breast cancer patients treated with oncologic resection of tumor, skin sparing breast reconstruction and ipsilateral ALND avoiding contralateral symmetry surgery, and data of total and positive axillary node counts, patient distribution as per pathological node (pN) stages and LNR subgroups, and DFS and OS at follow-up date when all patients of high-risk LNR died.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u0026nbsp; Six years follow-up of patients who were treated with alternative OPS model indicated spontaneous enlargement of all operated breasts, perfect symmetrisation, and no loco-regional recurrence.\u003c/p\u003e\n\u003cp\u003eThe median DFS and overall OS on December 2022 were 49\u003csup\u003e.\u003c/sup\u003e23 and 52\u003csup\u003e.\u003c/sup\u003e63 months respectively. Significant statistical difference was observed of the distribution of patients among pN stages and LNR subgroups (\u003cem\u003ep = 0\u003c/em\u003e\u003csup\u003e\u003cem\u003e.\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e000001)\u003c/em\u003e and of estimated mean DFS between low- and high-risk (\u003cem\u003ep = 0\u003c/em\u003e\u003csup\u003e\u003cem\u003e.\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e000003\u003c/em\u003e), and intermediate- and high-risk LNR (\u003cem\u003ep = 0\u003c/em\u003e\u003csup\u003e\u003cem\u003e.\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e000115\u003c/em\u003e), and of OS between low- and high-risk (\u003cem\u003ep = 0\u003c/em\u003e\u003csup\u003e\u003cem\u003e.\u003c/em\u003e\u003c/sup\u003e\u003cem\u003e000041\u003c/em\u003e), and intermediate- and high-risk LNR (\u003cem\u003ep = 0.000161\u003c/em\u003e) subgroups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eIpsilateral ALND model of OPS is a simpler therapeutic procedure causing spontaneous enlargement of the treated cancer bearing breast leading to almost natural symmetrisation, de-escalate surgical work load and is a safer procedure. ALND is powerful independent forecaster of breast cancer prognosis too.\u0026nbsp;\u003cstrong\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"De-escalation of oncoplastic surgery and prediction of breast cancer survival beyond serial axillary dissection – A prospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-04 00:18:18","doi":"10.21203/rs.3.rs-7316406/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":"e1957966-af13-4a44-a445-b44bfe26c1b4","owner":[],"postedDate":"September 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":54045601,"name":"Biological sciences/Cancer"},{"id":54045602,"name":"Health sciences/Oncology"}],"tags":[],"updatedAt":"2025-09-29T04:38:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-04 00:18:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7316406","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7316406","identity":"rs-7316406","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}