Low pectoralis major muscle mass predicts the risk of post-surgical bleeding after mastectomy in patients with breast cancer

Low pectoralis major muscle mass predicts the risk of post-surgical bleeding after mastectomy in patients with breast cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Low pectoralis major muscle mass predicts the risk of post-surgical bleeding after mastectomy in patients with breast cancer Ryoko Iji, Takaaki Oba, Reina Miyazawa, Ayaka Kitazawa, Nami Kiyosawa, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8846876/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Purpose Post-surgical bleeding is a clinically relevant complication after mastectomy. Although high body mass index (BMI) is associated with the risk of this complication, the impact of regional skeletal muscle mass adjacent to the operative field remains unclear. This study aims to evaluate the association between pectoralis major muscle mass and post-surgical bleeding after mastectomy in patients with breast cancer. Methods We retrospectively analyzed 669 patients who underwent mastectomy between 2015 and 2022, involving a total of 709 breasts. The pectoralis major muscle area was measured using preoperative computed tomography (CT) at the Th2 level, and the pectoralis major muscle index (PMI) was then calculated as the muscle area divided by height squared. We analyzed the association between BMI and PMI, and the incidence of post-surgical bleeding. Results Post-surgical bleeding occurred in 42 cases (5.9%). Patients who experienced bleeding had significantly higher BMI (26.1 ± 4.7 vs. 22.8 ± 3.8, p < 0.0001) and lower PMI (2.76 ± 0.69 vs. 3.12 ± 0.82, p < 0.001) than those without bleeding. BMI and PMI were weakly correlated (r = 0.16). On multivariate analysis, high BMI (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.27–1.52, p < 0.0001) and low PMI (HR 0.18, 95% CI 0.09–0.32, p < 0.0001) were independently associated with an increased risk of post-surgical bleeding. Combined stratification demonstrated that patients with a high BMI and low PMI had the highest incidence of bleeding (20.1%), whereas those with a low BMI and high PMI had the lowest risk (1.3%). Conclusions Low PMI and high BMI are independent predictors of post-surgical bleeding after mastectomy. Assessment of regional muscle mass using preoperative CT may enhance perioperative risk stratification in patients with breast cancer. Pectoralis major muscle index Body mass index Post-surgical bleeding Mastectomy Breast cancer Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Breast cancer is the most common solid malignancy in women and remains a major cause of cancer-related mortality worldwide [ 1 ]. Surgery has long been be the cornerstone of treatment for early-stage breast cancer even in the era of advances in systemic therapy and radiotherapy. Breast-conserving surgery (BCS) followed by whole-breast irradiation is widely accepted for women with relatively small tumors, whereas mastectomy is still frequently selected for patients with extensive disease, contraindications to irradiation, or according to patients’ preference [ 2 – 4 ]. However, mastectomy carries a higher risk of postoperative complications, including post-surgical bleeding, surgical site infection, and skin flap necrosis than BCS [ 5 ]. Among these, post-surgical bleeding is particularly clinically important because it may necessitate blood transfusion or reoperation and can prolong hospitalization [ 6 ]. Body composition has been recognized as an important factor affecting the risk of postoperative complications in breast cancer surgery [ 7 ]. In particular, elevated body mass index (BMI) has long been identified as a risk factor for wound complications, infections, and post-surgical bleeding [ 7 – 9 ]. However, BMI is a crude measure of body composition and does not distinguish between adipose and lean mass. In parallel, growing evidence suggests that sarcopenia, characterized by reduced skeletal muscle mass, is associated with higher risk of postoperative complications and poorer outcomes in patients undergoing surgery for various solid malignancies [ 10 , 11 ]. In these settings, the skeletal muscle index (SMI), which is calculated as the ratio of skeletal muscle area at the third lumbar vertebral level (L3) on computed tomography (CT) divided by height squared (m 2 ), has been widely used as an objective indicator of muscle mass [ 12 – 14 ]. Low SMI has been increasingly recognized as a marker of frailty and impaired tissue integrity, and has been associated with adverse surgical outcomes, including wound complications and bleeding in surgery for various solid malignancies [ 15 , 16 ]. Consistent with this concept, we previously reported that low SMI when combined with high BMI was associated with the increased risk of post-surgical bleeding after mastectomy in patients with breast cancer [ 17 ]. Despite this, major limitations of applying L3-based SMI to breast cancer surgery are that abdominal CT is not routinely performed in patients with early-stage disease and that L3-based measurements may not adequately reflect local tissue characteristics at the operative field. Importantly, pectoralis major muscle is routinely exposed during mastectomy. Because post-surgical bleeding most commonly originates from vessels within the subcutaneous tissue or on the surface of the pectoralis major muscle, muscle mass directly adjacent to the operative field may be more relevant to bleeding risk than global skeletal muscle mass. In this regard, chest CT is routinely obtained for staging in patients with breast cancer, and the pectoralis major muscle is clearly visualized. Hence, focusing on the pectoralis major muscle, which is directly involved in the operative field of mastectomy represents clinically relevant approach to evaluating bleeding risk after mastectomy. To date, no study has evaluated the clinical significance of pectoralis major muscle mass as a risk factor for post-surgical complications. The present study aimed to clarify the impact of the pectoralis major muscle mass on post-surgical bleeding after mastectomy in patients with breast cancer. Using preoperative chest CT images, we quantified the pectoralis major muscle mass and evaluated its association, together with BMI and their combination, with the risk of post-surgical bleeding. Methods Patients and study design We conducted a retrospective review of patients with breast cancer who underwent surgery at Shinshu University Hospital between January 2015 and December 2022. Eligible patients met the following criteria: (1) pathologically confirmed breast cancer established by core needle biopsy or vacuum-assisted biopsy, (2) preoperative CT image is available, and (3) treated with mastectomy. The type of axillary surgical procedure (none, sentinel lymph node biopsy [SLNB], or axillary dissection [Ax]) did not affect eligibility for inclusion in this study. Exclusion criteria were: (1) patients who underwent immediate one-stage reconstruction and (2) male patients. A total of 669 patients met the criteria. Because 20 patients had synchronous bilateral disease and underwent bilateral mastectomy, 709 breasts were included in the analysis, and all analyses were performed on a per-breast basis ( Supplementary Fig. 1 ). Node-positive patients received neoadjuvant chemotherapy (NAC) with either triweekly fluorouracil–epirubicin–cyclophosphamide (FEC; 500 mg/m² fluorouracil, 100 mg/m² epirubicin, 500 mg/m² cyclophosphamide) or epirubicin–cyclophosphamide (EC; 90 mg/m² epirubicin, 500 mg/m² cyclophosphamide), followed by taxane-based regimens (docetaxel 75 mg/m² every three weeks or weekly paclitaxel 80 mg/m²), each administered for four cycles. Patients with human epidermal growth factor receptor 2 (HER2)-positive or triple-negative (TN) breast cancer could also receive NAC irrespective of nodal status. In HER2-positive cases, trastuzumab (6 mg/kg triweekly or 2 mg/kg weekly) with or without pertuzumab (420 mg triweekly) was administered concurrently with taxanes. The study complied with institutional and national ethical guidelines and the principles of the Declaration of Helsinki. This study was approved by the local ethics committee on the clinical investigation of Shinshu University (no. 6712). Written informed consent was waived owing to the opt-out policy on the institutional website. All data were anonymized before analysis. Data collection We extracted clinical and pathological data from medical records. Clinical variables, included age, presence of comorbidity (hypertension, dyslipidemia, and diabetes), presence of anticoagulant therapy and antiplatelet therapy, platelet count in peripheral blood, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), laterality, height, body weight, presence of NAC, surgical procedure, surgeon category, operation time, intraoperative blood loss (ml), drainage duration (day), hospital stay (day) Pathological variables included histological type of tumor, pathological tumor size, lymph node status, estrogen receptor (ER) status, progesterone receptor (PgR) status, and HER2 status. Surgeons were classified as residents or faculty members, with faculty defined as board-certified specialists of the Japan Breast Cancer Society. At our institution, resident-performed surgeries were always performed under direct supervision, with a faculty surgeon assigned as the first assistant. Breast cancer subtypes were categorized as follows: luminal (ER and/or PgR-positive and HER2-negative), luminal HER2 (ER and/or PR-positive and HER2-positive), HER2-enriched (ER- and PR-negative, HER2-positive), and TN (ER-, PR-, and HER2-negative). For mastectomy with SLNB or simple mastectomy, a 15-Fr J-VAC® (Johnson & Johnson, NJ) drain was placed in the subcutaneous space. When Ax was performed, an additional axillary drain was inserted at axilla. Drainage duration was defined as the time from surgery to removal of all drains. At our institution, oral antiplatelet therapy was discontinued 7–14 days before surgery, whereas direct oral anticoagulant therapy was discontinued 1 day before surgery. Measurement of pectoralis major muscle mass index (PMI) Preoperative CT was routinely performed within 1 month prior to the surgery. For patients receiving NAC, CT was performed > 3 weeks after the completion of NAC. The pectoralis major muscle area (PMA) was assessed on axial CT slices at the level of the second thoracic vertebra (Th2). Using EV Insite R software (PSP Corporation, Tokyo), the PMA was semiautomatically delineated within attenuation thresholds of − 29 to 150 Hounsfield units and expressed in cm². Pectoralis major muscle mass index (PMI) was calculated as the ratio of PMA divided by height squared (m 2 ). BMI was calculated as body weight (kg) within 1 month prior to the surgery divided by height squared (m 2 ). Cutoff values for BMI and PMI associated with post-surgical bleeding were determined using receiver operating characteristic (ROC) curve analysis. Definition of post-surgical bleeding Wounds were routinely compressed using a bust band to minimize postoperative bleeding. If we suspected post-surgical bleeding with swelling of the wound or the continuous bloody discharge from the J-VAC® drain, hemostasis was attempted by placing a pile of gauze through manual compression at the suspected bleeding point. Post-surgical bleeding was defined as either: (1) hemorrhage requiring postoperative manual compression, or (2) > 100 mL of bloody output from the J-VAC® drain by the morning of postoperative day 1. In patients undergoing mastectomy with Ax, a bloody discharge of > 100 ml from either of the two J-VAC® drains was considered post-surgical bleeding. The J-VAC® drain was removed when the drainage volume was < 25 ml per day. These criteria were consistently applied according to institutional postoperative management protocols. Statistical analyses Categorical variables were compared using chi-square tests, whereas continuous variables were analyzed with two-sided t -tests. Logistic regression models were used for univariate and multivariate assessments of bleeding-related factors. Variables with p < 0.05 on univariate analysis were included in the multivariate model. All statistical analyses were performed using GraphPad Prism 9.3.1 (GraphPad Software, CA, USA), and p < 0.05 was considered statistically significant. Results Patient characteristics The clinicopathological characteristics of the patients are summarized in Table 1 . The mean age of the patients (± standard deviation) was 59.9 ± 13.8 years. Hypertension, dyslipidemia, and diabetes were present in 195 (27.5%), 124 (17.5%), and 52 (7.3%) patients, respectively. Oral anticoagulant and antiplatelet therapies were administered in 17 (2.4%) and 19 (2.7%) patients, respectively. The mean values of coagulation-related parameters including platelet count, PT-INR, and APTT were 25.6 ± 7.1 ×10⁴/µL, 1.00 ± 0.12, and 27.0 ± 4.2 seconds, respectively. Breast cancer was located in the right breast in 329 cases (46.4%) and on the left breast in 380 cases (53.6%). NAC was administered to 171 patients (24.1%). Regarding axillary management, 415 breasts (58.5%) underwent mastectomy with SLNB or none, while Ax was performed in 294 breasts (41.5%). Surgery was performed by a resident in 402 cases (56.6%) and by a faculty in 307 cases (43.4%). The mean operation time was 205.1 ± 67.4 mins, and the mean intraoperative blood loss was 85.5 ± 73.2 mL. The mean duration of postoperative drainage was 4.3 ± 1.7 days, and the mean postoperative hospital stay was 7.0 ± 2.5 days. With regard to pathological findings, ductal carcinoma was the most frequent histological type (574 cases, 80.9%), followed by lobular carcinoma (50 cases, 7.1%) and other histological subtypes (85 cases, 12.0%). Tumors measuring ≤ 2.0 cm were observed in 359 cases (50.6%), whereas tumors > 2.0 cm were present in 350 cases (49.4%). Pathological lymph node metastasis was identified in 198 cases (27.9%). Most patients had stage II–III disease (573 cases, 80.8%), whereas stage 0–I and stage IV disease accounted for 121 (17.1%) and 15 cases (2.1%), respectively. Regarding breast cancer subtype, luminal was the most common (446 cases, 62.9%), followed by luminal HER2 (106 cases, 15.0%), TN (90 cases, 12.7%), and HER2-enriched (59 cases, 8.3%). Clinicopathological characteristics stratified by post-surgical bleeding Post-surgical bleeding occurred in 42 (5.9%) breasts. The patients were divided into no-bleeding (n = 667) and bleeding (n = 42) groups, and their clinicopathological characteristics were compared ( Table 1 ). No significant differences were observed between the two groups with respect to age, comorbidities (hypertension, dyslipidemia, or diabetes), use of oral antiplatelet or anticoagulant therapy, coagulation-related parameters (platelet count, PT-INR, APTT) or breast cancer laterality. Variables reflecting the disease extent showed consistent trends between the two groups. Although no significant differences were observed in tumor size, histological type, or intrinsic subtype between the two groups, patients in the bleeding group were significantly less likely to have received NAC (4.7% vs. 25.3%, p = 0.01), undergone Ax (19.0% vs. 39.0%, p = 0.001), or have pathological lymph node metastasis (7.1% vs. 29.2%, p = 0.001). Consequently, stage 0–I disease was more prevalent in the bleeding group (57.1% vs. 14.5%, p = 0.001). Regarding perioperative clinical factors, no significant differences in the operation time or intraoperative blood loss were observed. The surgeon category differed between the groups, with faculty surgeons accounting for a significantly higher proportion of the bleeding group (59.5% vs. 42.2%, p = 0.04). The duration of postoperative drainage was significantly longer in the bleeding group than in the no-bleeding group (5.8 ± 1.7 vs. 3.3 ± 1.2 days, p < 0.001). Postoperative length of hospital stay also tended to be longer in the bleeding group, although the difference did not reach statistical significance (7.8 ± 2.4 vs. 7.1 ± 2.5 days, p = 0.08). Comparison of BMI and PMI according to post-surgical bleeding We next compared BMI and PMI between patients with and without post-surgical bleeding. BMI was significantly higher in the bleeding group (26.1 ± 4.7) than in the no-bleeding group (22.8 ± 3.8) ( p < 0.0001) (Fig. 1 A). On the other hand, PMI was significantly lower in the bleeding group (2.76 ± 0.69) than in the no-bleeding group (3.12 ± 0.82) ( p < 0.001) (Fig. 1 B). Incidence of post-surgical bleeding according to BMI and PMI Given that patients who experienced post-surgical bleeding tended to have a higher BMI and lower PMI, we next compared the incidence of bleeding across BMI- and PMI-defined subgroups. Patients were divided into high and low BMI or PMI groups according to the cutoff values determined by ROC curve analysis for post-surgical bleeding. The cutoff values were 23.7 for BMI (area under the curve [AUC] = 0.71; sensitivity/specificity = 0.64) and 2.90 for PMI (AUC = 0.64; sensitivity/specificity = 0.59). In the BMI analysis, patients in the BMI-high group exhibited a significantly higher incidence of post-surgical bleeding (10.9%) than those in the BMI-low group (3.1%) ( p < 0.0001) (Fig. 2 , Supplementary Table 1 ). Conversely, the PMI-low group demonstrated a significantly higher incidence of bleeding (8.4%) than the PMI-high group (4.1%) ( p = 0.02) (Fig. 2 , Supplementary Table 2 ). Taken together, these findings indicate that a high BMI and low PMI are significant risk factors for post-surgical bleeding. Correlation between preoperative BMI and PMI In our previous study, a moderate positive correlation between BMI and SMI was observed (r = 0.54) in a breast cancer cohort [ 17 ]. Hypothesizing that PMI would also positively correlate with BMI, we investigated the correlation between BMI and PMI. We found that PMI showed a weak positive correlation with BMI (r = 0.16) (Fig. 3 ), indicating that PMI and BMI capture different components of body composition and function as independent factors. Impact of BMI and PMI as risk factors for post-surgical bleeding Next, we explored independent risk factors for postsurgical bleeding using univariate and multivariate analyses. Because BMI and PMI showed a weak correlation (Fig. 3 ), both variables were included in the univariate and multivariate models. Univariate analysis revealed that axillary procedure (none or SLNB) (hazard ratio [HR], 3.19; 95% confidence interval [CI], 1.53–7.56; p = 0.001), low PMI (HR, 0.51; 95% CI, 0.31–0.78; p = 0.002), and high BMI (HR, 1.12; 95% CI, 1.10–1.25; p < 0.0001) were significantly associated with post-surgical bleeding ( Table 2 ). In the multivariate logistic regression analysis, axillary procedure (none or SLNB) (HR, 5.07; 95% CI, 2.27–12.8; p < 0.0001), low PMI (HR, 0.18; 95% CI, 0.09–0.32; p < 0.0001), and high BMI (HR, 1.38; 95% CI, 1.27–1.52; p < 0.0001) remained significant ( Table 2 ), indicating that both higher BMI and lower PMI independently increase the risk of this complication. Combinatorial impact of BMI and PMI as a risk factor for post-surgical bleeding As shown in the preceding analyses, high BMI and low PMI may be independent risk factors for postsurgical bleeding. To evaluate their combined effect, we stratified the patients into four BMI-PMI categories (BMI-low/PMI-high, BMI-low/PMI-low, BMI-high/PMI-high, and BMI-high/PMI-low). The BMI-high/PMI-low group showed the most pronounced susceptibility to bleeding (20.1%), with progressively lower rates observed in the BMI-high/PMI-high (7.4%), BMI-low/PMI-low (4.8%), and BMI-low/PMI-high (1.3%) groups ( p < 0.001) (Fig. 4 , Supplementary Table 3 ). Discussion This study demonstrated that an elevated BMI and reduced PMI were significant risk factors for post-surgical bleeding after mastectomy. Notably, their combined assessment identified patients at an elevated risk of this complication more effectively than either factor alone. To the best of our knowledge, this is the first study to show that the pectoralis major muscle mass may contribute to bleeding risk in patients with breast cancer undergoing mastectomy. The primary sources of post-surgical bleeding following mastectomy are likely inadequately sealed vessels on the surface of the pectoralis major muscle, within the subcutaneous fat, or in the axillary region. Since a wider extent of tissue dissection is generally associated with an increased risk of post-surgical bleeding [ 18 ], Ax would be expected to confer a higher bleeding risk than SLNB. However, in line with the results of this study, our previous study demonstrated that Ax was associated with a lower risk of post-surgical bleeding than SLNB. This paradoxical result suggests that in patients undergoing mastectomy, post-surgical bleeding is more likely to originate from the surface of the pectoralis major muscle or subcutaneous tissue than from the axillary region. In patients with high BMI, abundant subcutaneous fat may obscure small vessels and hinder meticulous hemostasis, resulting in an increased risk of inadequate ligation and subsequent bleeding. This is consistent with the higher incidence of post-surgical bleeding observed in patients with an elevated BMI in this study. Moreover, patients with a low PMI tend to have an atrophic pectoralis major muscle, which may increase the fragility of the vessels running over the muscle, thereby predisposing them to post-surgical bleeding. Taken together, these findings suggest that excess subcutaneous fat and reduced pectoralis major muscle mass, represented by high BMI and low PMI, are synergistically associated with an increased risk of post-surgical bleeding after mastectomy. In our previous study, SMI assessed at the L3 level was not a significant risk factor for post-surgical bleeding when considered alone [ 17 ]. However, when SMI was normalized to BMI, the resulting SMI-to-BMI ratio became a robust predictor of post-surgical bleeding, highlighting the importance of relative muscle mass in the context of overall adiposity rather than absolute skeletal muscle quantity. These findings suggested that sarcopenia is insufficient to explain bleeding susceptibility unless accompanied by excess adiposity, a condition conceptually aligned with sarcopenic obesity [ 19 , 20 ]. In contrast, in the present study, PMI showed only a very weak correlation with BMI, and a low PMI was independently associated with post-surgical bleeding, even without normalization for BMI. This discrepancy highlights the fundamental differences between global muscle indices and region-specific muscle assessments. While L3-based SMI reflects the overall trunk musculature and requires adjustment for body weight to capture clinically relevant vulnerability, PMI represents the local muscle mass adjacent to the operative field and may directly influence tissue integrity and vulnerability during surgery for breast cancer. Consequently, PMI and BMI function as largely independent risk factors, and their combination identifies patients at particularly high risk of post-surgical bleeding after mastectomy. Interestingly, the surgeon category was associated with post-surgical bleeding in our cohort, with a higher incidence observed in faculty-performed procedures, as shown in Table 1 . This finding appears counterintuitive given that surgical experience is generally associated with improved perioperative outcomes [ 21 – 23 ]. Several factors specific to breast surgery may explain these findings. First, mastectomy is a highly standardized procedure with well-established operative steps, routine drain placement, and institutional protocols for postoperative compression and monitoring, which may attenuate the differences attributable to individual techniques. Second, resident operations are typically conducted under the supervision of direct faculty members. Indeed, at our institution, all resident-performed breast surgeries were conducted by a faculty surgeon who served as the first assistant. This mandatory supervision system likely ensures consistent intraoperative hemostatic quality and mitigates differences related to surgeon experience. Consistent with this notion, previous large database analyses have shown that trainee participation in breast surgery does not increase the incidence of early postoperative complications [ 24 ]. Third, faculty surgeons were more likely to be assigned to technically demanding or high-risk cases, including those with a higher BMI. Such case allocations may partially account for the increased risk of bleeding observed in surgeries performed by faculty members. Finally, experience-based effects may become more apparent in technically novel and/or complex approaches such as endoscopic/robotic surgery, where measurable learning curves have been reported [ 25 ], rather than in conventional mastectomy. Collectively, these considerations suggest that in routine mastectomy practice, patient-related factors (BMI and PMI) appear to play a more prominent role than operator-related factors in determining post-surgical bleeding risk. This study has some limitations. First, this was a retrospective analysis conducted at a single institution, which may be associated with a selection bias. Second, the number of post-surgical bleeding events was relatively small, potentially limiting the statistical power of the multivariable analyses. Third, post-surgical bleeding was defined based on early postoperative clinical criteria, which may not fully capture minor or late-onset bleeding events. Finally, as the study population consisted exclusively of Japanese patients, the generalizability of these findings to other populations remains uncertain. To overcome these limitations, prospective multicenter studies with larger and more diverse cohorts are warranted. Conclusions This study demonstrates that BMI and PMI are independent predictors of post-surgical bleeding after mastectomy for breast cancer. The preoperative assessment of body composition may help identify patients with a higher risk of bleeding. Abbreviations BCS, breast-conserving surgery; BMI, body mass index; SMI, skeletal muscle index; L3, third lumbar vertebral level; CT, computed tomography; SLNB, sentinel lymph node biopsy; Ax, axillary dissection; NAC, neoadjuvant chemotherapy; FEC, fluorouracil–epirubicin–cyclophosphamide; EC, epirubicin–cyclophosphamide; HER2, human epidermal growth factor receptor 2; TN, triple-negative; PT-INR, prothrombin time-international normalized ratio; APTT, activated partial thromboplastin time; ER, estrogen receptor; PgR, progesterone receptor; PMI, pectoralis major muscle mass index; PMA, pectoralis major muscle area; Th2, second thoracic vertebra; ROC, receiver operating characteristic; HR, hazard ratio; CI, confidence interval Declarations Acknowledgement: We would like to thank Editage (www.editage.com) for English language editing. Funding This work was not funded by any grant. Competing Interests The authors declare that they have no competing interests. Author Contributions Ryoko Iji and Takaaki Oba designed the study. Reina Miyazawa, Ayaka Kitazawa, Nami Kiyosawa, Shota Katsuyama, Hiroki Morikawa, Masatsugu Amitani, Tatsunori Chino, Tadafumi Sshimizu, Mayu Ono, Keiko Natori and Toshiharu Kanai collected the clinical data. Ryoko Iji and Takaaki Oba performed the statistical analysis. The draft manuscript was prepared by Ryoko Iji, Takaaki Oba and Ken-ichi Ito. All authors read and approved the final manuscript. Data Availability The data supporting the findings of this work are available from the authors upon reasonable request. Ethics approval: The study was conducted in accordance with the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013) and approved by the ethics committee of Shinshu University (approval no. 6712). Consent to participate: Given the retrospective nature of the study using anonymized data, the requirement for written informed consent was waived. 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J Am Coll Surg 221:988–994 Soomro NA, Hashimoto DA, Porteous AJ, Ridley CJA, Marsh WJ, Ditto R, Roy S (2020) Systematic review of learning curves in robot-assisted surgery. BJS Open 4:27–44 Tables Tables 1 and 2 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Supplementaryfigure.pptx Supplemetaryfigurelegends.docx SupplementaryTable1.docx SupplementaryTable2.docx SupplementaryTable3.docx Tables.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 12 Apr, 2026 Reviewers agreed at journal 23 Mar, 2026 Reviewers invited by journal 20 Mar, 2026 Editor assigned by journal 11 Feb, 2026 Submission checks completed at journal 11 Feb, 2026 First submitted to journal 10 Feb, 2026 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8846876","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":610695257,"identity":"89a11a32-0252-4267-afe4-b092cefae4b8","order_by":0,"name":"Ryoko Iji","email":"","orcid":"","institution":"Shinshu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ryoko","middleName":"","lastName":"Iji","suffix":""},{"id":610695258,"identity":"6c94dadd-c071-4b48-a7b2-e21afd35b851","order_by":1,"name":"Takaaki Oba","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYFACNgYGxgYGOQYJIAlEUMCDWwMPVIsx6VoSGyQYGJC04AH27McSP3zcYZc+f3Zz28OfOw4zGBxgfviBQeYOblt40g5LzjyTnLvhzsF2Y94zIC1sxhIMPM/wOCy9QZq3jTl3g0RimzRj2+H6DQcYzIDih3Fr4X/e/Ju3rT5dfkZim+TPNpAt7N/wa5FIOwa05XACw43ENglesBYeArbceJZmOfPMccMNQC1AvekMkod5iiUS8PiFvT/N+MbHHdXy8jPSnwEdZs3Ad7x944ePPbhDDAtgBuLEngOkaAGDH6RrGQWjYBSMgmELAOxtVS2VbpnrAAAAAElFTkSuQmCC","orcid":"","institution":"Shinshu University School of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Takaaki","middleName":"","lastName":"Oba","suffix":""},{"id":610695259,"identity":"ddc137b4-1a04-4c47-8012-cf71c707eb35","order_by":2,"name":"Reina Miyazawa","email":"","orcid":"","institution":"Shinshu University School of 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Medicine","correspondingAuthor":false,"prefix":"","firstName":"Keiko","middleName":"","lastName":"Natori","suffix":""},{"id":610695269,"identity":"f2e13b18-7c95-4832-b42c-913d617f184f","order_by":12,"name":"Toshiharu Kanai","email":"","orcid":"","institution":"Shinshu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Toshiharu","middleName":"","lastName":"Kanai","suffix":""},{"id":610695270,"identity":"246608ef-e24a-4037-b459-a963aba690fb","order_by":13,"name":"Ken-ichi Ito","email":"","orcid":"","institution":"Shinshu University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ken-ichi","middleName":"","lastName":"Ito","suffix":""}],"badges":[],"createdAt":"2026-02-11 04:08:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8846876/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8846876/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105456644,"identity":"0e6de779-cdf6-45c7-9dc2-2f29a035dd56","added_by":"auto","created_at":"2026-03-26 09:15:06","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":77383,"visible":true,"origin":"","legend":"\u003cp\u003eViolin plot for BMI and PMI in the bleeding group and the no-bleeding group. The left panel (A) shows the result of BMI (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.0001), while the right panel (B) of PMI (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eBMI: Body mass index, PMI: Pectoralis major muscle index\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/6662ff2a477ae71190508fe1.png"},{"id":105456635,"identity":"02c7da2d-0d37-4236-9468-acd3f3216d91","added_by":"auto","created_at":"2026-03-26 09:15:05","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":61037,"visible":true,"origin":"","legend":"\u003cp\u003eIncidence of post-surgical bleeding according to BMI (Left) and PMI (Right). Specific percentages and \u003cem\u003ep\u003c/em\u003e values are indicated on the data panel.\u003c/p\u003e\n\u003cp\u003eBMI: Body mass index, PMI: Pectoralis major muscle index\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/27d96795ff13849bce5d65bf.png"},{"id":105456634,"identity":"c871f20a-4fe9-4a4a-887e-c18aa7694982","added_by":"auto","created_at":"2026-03-26 09:15:05","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":40996,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot of PMI against BMI. Correlation is shown using Pearson correlation coefficients (r) (r = 0.16).\u003c/p\u003e\n\u003cp\u003eBMI: Body mass index, PMI: Pectoralis major muscle index\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/db7005e0507572bb659a7a0c.png"},{"id":105566974,"identity":"7bca7015-68bb-4bdd-98ed-8b6c4ab0f029","added_by":"auto","created_at":"2026-03-27 12:57:54","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":64231,"visible":true,"origin":"","legend":"\u003cp\u003eIncidence of post-surgical bleeding in the BMI-low/PMI-high, the BMI-low/PMI-low, BMI-high/PMI-high, and BMI-high/PMI-low group. Specific percentages and \u003cem\u003ep\u003c/em\u003evalues are indicated on the data panel.\u003c/p\u003e\n\u003cp\u003eBMI: Body mass index, PMI: Pectoralis major muscle index\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/7afb274f7dcceef285a2f701.png"},{"id":105570075,"identity":"3e4f2ed4-1801-4a41-bd8d-f1c192cc833a","added_by":"auto","created_at":"2026-03-27 13:14:24","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1040995,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/ad201294-42dd-4e0a-92cc-fa064c46dbc1.pdf"},{"id":105456643,"identity":"9d15596f-3e78-4c96-a45f-abadcda9cb5f","added_by":"auto","created_at":"2026-03-26 09:15:06","extension":"pptx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":41955,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfigure.pptx","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/c423fcfc450efa6f41f3b023.pptx"},{"id":105456638,"identity":"bea4afe8-47ed-479d-9890-d2821e5ddf64","added_by":"auto","created_at":"2026-03-26 09:15:05","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":34271,"visible":true,"origin":"","legend":"","description":"","filename":"Supplemetaryfigurelegends.docx","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/fbdb28ed934148dc35f2d6e9.docx"},{"id":105565698,"identity":"5cb5a145-055f-4f46-bbd4-213f4ff76f73","added_by":"auto","created_at":"2026-03-27 12:54:05","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16845,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/12cf5fb10b089b4e54f69a05.docx"},{"id":105456642,"identity":"543808f7-21fd-49c2-82e1-b04bfd321204","added_by":"auto","created_at":"2026-03-26 09:15:05","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":16825,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/0e08c26a7d20931f982498a7.docx"},{"id":105566478,"identity":"23dd614e-c8f4-4ffa-99dd-ae53ab2ec295","added_by":"auto","created_at":"2026-03-27 12:56:29","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":17296,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable3.docx","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/caa51a2804ebf659f9a29415.docx"},{"id":105565936,"identity":"d5795d24-faf6-490a-a59c-640baadf1fd4","added_by":"auto","created_at":"2026-03-27 12:54:48","extension":"docx","order_by":6,"title":"","display":"","copyAsset":false,"role":"supplement","size":53303,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.docx","url":"https://assets-eu.researchsquare.com/files/rs-8846876/v1/7dda916fe12c55c2f3e79a31.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Low pectoralis major muscle mass predicts the risk of post-surgical bleeding after mastectomy in patients with breast cancer","fulltext":[{"header":"Background","content":"\u003cp\u003eBreast cancer is the most common solid malignancy in women and remains a major cause of cancer-related mortality worldwide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Surgery has long been be the cornerstone of treatment for early-stage breast cancer even in the era of advances in systemic therapy and radiotherapy. Breast-conserving surgery (BCS) followed by whole-breast irradiation is widely accepted for women with relatively small tumors, whereas mastectomy is still frequently selected for patients with extensive disease, contraindications to irradiation, or according to patients\u0026rsquo; preference [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, mastectomy carries a higher risk of postoperative complications, including post-surgical bleeding, surgical site infection, and skin flap necrosis than BCS [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Among these, post-surgical bleeding is particularly clinically important because it may necessitate blood transfusion or reoperation and can prolong hospitalization [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBody composition has been recognized as an important factor affecting the risk of postoperative complications in breast cancer surgery [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In particular, elevated body mass index (BMI) has long been identified as a risk factor for wound complications, infections, and post-surgical bleeding [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, BMI is a crude measure of body composition and does not distinguish between adipose and lean mass. In parallel, growing evidence suggests that sarcopenia, characterized by reduced skeletal muscle mass, is associated with higher risk of postoperative complications and poorer outcomes in patients undergoing surgery for various solid malignancies [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In these settings, the skeletal muscle index (SMI), which is calculated as the ratio of skeletal muscle area at the third lumbar vertebral level (L3) on computed tomography (CT) divided by height squared (m\u003csup\u003e2\u003c/sup\u003e), has been widely used as an objective indicator of muscle mass [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Low SMI has been increasingly recognized as a marker of frailty and impaired tissue integrity, and has been associated with adverse surgical outcomes, including wound complications and bleeding in surgery for various solid malignancies [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Consistent with this concept, we previously reported that low SMI when combined with high BMI was associated with the increased risk of post-surgical bleeding after mastectomy in patients with breast cancer [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite this, major limitations of applying L3-based SMI to breast cancer surgery are that abdominal CT is not routinely performed in patients with early-stage disease and that L3-based measurements may not adequately reflect local tissue characteristics at the operative field. Importantly, pectoralis major muscle is routinely exposed during mastectomy. Because post-surgical bleeding most commonly originates from vessels within the subcutaneous tissue or on the surface of the pectoralis major muscle, muscle mass directly adjacent to the operative field may be more relevant to bleeding risk than global skeletal muscle mass. In this regard, chest CT is routinely obtained for staging in patients with breast cancer, and the pectoralis major muscle is clearly visualized. Hence, focusing on the pectoralis major muscle, which is directly involved in the operative field of mastectomy represents clinically relevant approach to evaluating bleeding risk after mastectomy. To date, no study has evaluated the clinical significance of pectoralis major muscle mass as a risk factor for post-surgical complications.\u003c/p\u003e \u003cp\u003eThe present study aimed to clarify the impact of the pectoralis major muscle mass on post-surgical bleeding after mastectomy in patients with breast cancer. Using preoperative chest CT images, we quantified the pectoralis major muscle mass and evaluated its association, together with BMI and their combination, with the risk of post-surgical bleeding.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients and study design\u003c/h2\u003e \u003cp\u003e We conducted a retrospective review of patients with breast cancer who underwent surgery at Shinshu University Hospital between January 2015 and December 2022. Eligible patients met the following criteria: (1) pathologically confirmed breast cancer established by core needle biopsy or vacuum-assisted biopsy, (2) preoperative CT image is available, and (3) treated with mastectomy. The type of axillary surgical procedure (none, sentinel lymph node biopsy [SLNB], or axillary dissection [Ax]) did not affect eligibility for inclusion in this study. Exclusion criteria were: (1) patients who underwent immediate one-stage reconstruction and (2) male patients. A total of 669 patients met the criteria. Because 20 patients had synchronous bilateral disease and underwent bilateral mastectomy, 709 breasts were included in the analysis, and all analyses were performed on a per-breast basis (\u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e).\u003c/p\u003e \u003cp\u003eNode-positive patients received neoadjuvant chemotherapy (NAC) with either triweekly fluorouracil\u0026ndash;epirubicin\u0026ndash;cyclophosphamide (FEC; 500 mg/m\u0026sup2; fluorouracil, 100 mg/m\u0026sup2; epirubicin, 500 mg/m\u0026sup2; cyclophosphamide) or epirubicin\u0026ndash;cyclophosphamide (EC; 90 mg/m\u0026sup2; epirubicin, 500 mg/m\u0026sup2; cyclophosphamide), followed by taxane-based regimens (docetaxel 75 mg/m\u0026sup2; every three weeks or weekly paclitaxel 80 mg/m\u0026sup2;), each administered for four cycles. Patients with human epidermal growth factor receptor 2 (HER2)-positive or triple-negative (TN) breast cancer could also receive NAC irrespective of nodal status. In HER2-positive cases, trastuzumab (6 mg/kg triweekly or 2 mg/kg weekly) with or without pertuzumab (420 mg triweekly) was administered concurrently with taxanes.\u003c/p\u003e \u003cp\u003e The study complied with institutional and national ethical guidelines and the principles of the Declaration of Helsinki. This study was approved by the local ethics committee on the clinical investigation of Shinshu University (no. 6712). Written informed consent was waived owing to the opt-out policy on the institutional website. All data were anonymized before analysis.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eWe extracted clinical and pathological data from medical records. Clinical variables, included age, presence of comorbidity (hypertension, dyslipidemia, and diabetes), presence of anticoagulant therapy and antiplatelet therapy, platelet count in peripheral blood, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), laterality, height, body weight, presence of NAC, surgical procedure, surgeon category, operation time, intraoperative blood loss (ml), drainage duration (day), hospital stay (day) Pathological variables included histological type of tumor, pathological tumor size, lymph node status, estrogen receptor (ER) status, progesterone receptor (PgR) status, and HER2 status. Surgeons were classified as residents or faculty members, with faculty defined as board-certified specialists of the Japan Breast Cancer Society. At our institution, resident-performed surgeries were always performed under direct supervision, with a faculty surgeon assigned as the first assistant.\u003c/p\u003e \u003cp\u003eBreast cancer subtypes were categorized as follows: luminal (ER and/or PgR-positive and HER2-negative), luminal HER2 (ER and/or PR-positive and HER2-positive), HER2-enriched (ER- and PR-negative, HER2-positive), and TN (ER-, PR-, and HER2-negative).\u003c/p\u003e \u003cp\u003eFor mastectomy with SLNB or simple mastectomy, a 15-Fr J-VAC\u0026reg; (Johnson \u0026amp; Johnson, NJ) drain was placed in the subcutaneous space. When Ax was performed, an additional axillary drain was inserted at axilla. Drainage duration was defined as the time from surgery to removal of all drains. At our institution, oral antiplatelet therapy was discontinued 7\u0026ndash;14 days before surgery, whereas direct oral anticoagulant therapy was discontinued 1 day before surgery.\u003c/p\u003e\n\u003ch3\u003eMeasurement of pectoralis major muscle mass index (PMI)\u003c/h3\u003e\n\u003cp\u003ePreoperative CT was routinely performed within 1 month prior to the surgery. For patients receiving NAC, CT was performed\u0026thinsp;\u0026gt;\u0026thinsp;3 weeks after the completion of NAC. The pectoralis major muscle area (PMA) was assessed on axial CT slices at the level of the second thoracic vertebra (Th2). Using EV Insite R software (PSP Corporation, Tokyo), the PMA was semiautomatically delineated within attenuation thresholds of \u0026minus;\u0026thinsp;29 to 150 Hounsfield units and expressed in cm\u0026sup2;. Pectoralis major muscle mass index (PMI) was calculated as the ratio of PMA divided by height squared (m\u003csup\u003e2\u003c/sup\u003e). BMI was calculated as body weight (kg) within 1 month prior to the surgery divided by height squared (m\u003csup\u003e2\u003c/sup\u003e). Cutoff values for BMI and PMI associated with post-surgical bleeding were determined using receiver operating characteristic (ROC) curve analysis.\u003c/p\u003e\n\u003ch3\u003eDefinition of post-surgical bleeding\u003c/h3\u003e\n\u003cp\u003eWounds were routinely compressed using a bust band to minimize postoperative bleeding. If we suspected post-surgical bleeding with swelling of the wound or the continuous bloody discharge from the J-VAC\u0026reg; drain, hemostasis was attempted by placing a pile of gauze through manual compression at the suspected bleeding point.\u003c/p\u003e \u003cp\u003ePost-surgical bleeding was defined as either: (1) hemorrhage requiring postoperative manual compression, or (2)\u0026thinsp;\u0026gt;\u0026thinsp;100 mL of bloody output from the J-VAC\u0026reg; drain by the morning of postoperative day 1. In patients undergoing mastectomy with Ax, a bloody discharge of \u0026gt;\u0026thinsp;100 ml from either of the two J-VAC\u0026reg; drains was considered post-surgical bleeding. The J-VAC\u0026reg; drain was removed when the drainage volume was \u0026lt;\u0026thinsp;25 ml per day. These criteria were consistently applied according to institutional postoperative management protocols.\u003c/p\u003e\n\u003ch3\u003eStatistical analyses\u003c/h3\u003e\n\u003cp\u003eCategorical variables were compared using chi-square tests, whereas continuous variables were analyzed with two-sided \u003cem\u003et\u003c/em\u003e-tests. Logistic regression models were used for univariate and multivariate assessments of bleeding-related factors. Variables with \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 on univariate analysis were included in the multivariate model. All statistical analyses were performed using GraphPad Prism 9.3.1 (GraphPad Software, CA, USA), and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eThe clinicopathological characteristics of the patients are summarized in \u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e. The mean age of the patients (\u0026plusmn;\u0026thinsp;standard deviation) was 59.9\u0026thinsp;\u0026plusmn;\u0026thinsp;13.8 years. Hypertension, dyslipidemia, and diabetes were present in 195 (27.5%), 124 (17.5%), and 52 (7.3%) patients, respectively. Oral anticoagulant and antiplatelet therapies were administered in 17 (2.4%) and 19 (2.7%) patients, respectively. The mean values of coagulation-related parameters including platelet count, PT-INR, and APTT were 25.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1 \u0026times;10⁴/\u0026micro;L, 1.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12, and 27.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2 seconds, respectively. Breast cancer was located in the right breast in 329 cases (46.4%) and on the left breast in 380 cases (53.6%). NAC was administered to 171 patients (24.1%). Regarding axillary management, 415 breasts (58.5%) underwent mastectomy with SLNB or none, while Ax was performed in 294 breasts (41.5%). Surgery was performed by a resident in 402 cases (56.6%) and by a faculty in 307 cases (43.4%). The mean operation time was 205.1\u0026thinsp;\u0026plusmn;\u0026thinsp;67.4 mins, and the mean intraoperative blood loss was 85.5\u0026thinsp;\u0026plusmn;\u0026thinsp;73.2 mL. The mean duration of postoperative drainage was 4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 days, and the mean postoperative hospital stay was 7.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 days. With regard to pathological findings, ductal carcinoma was the most frequent histological type (574 cases, 80.9%), followed by lobular carcinoma (50 cases, 7.1%) and other histological subtypes (85 cases, 12.0%). Tumors measuring\u0026thinsp;\u0026le;\u0026thinsp;2.0 cm were observed in 359 cases (50.6%), whereas tumors\u0026thinsp;\u0026gt;\u0026thinsp;2.0 cm were present in 350 cases (49.4%). Pathological lymph node metastasis was identified in 198 cases (27.9%). Most patients had stage II\u0026ndash;III disease (573 cases, 80.8%), whereas stage 0\u0026ndash;I and stage IV disease accounted for 121 (17.1%) and 15 cases (2.1%), respectively. Regarding breast cancer subtype, luminal was the most common (446 cases, 62.9%), followed by luminal HER2 (106 cases, 15.0%), TN (90 cases, 12.7%), and HER2-enriched (59 cases, 8.3%).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eClinicopathological characteristics stratified by post-surgical bleeding\u003c/h3\u003e\n\u003cp\u003ePost-surgical bleeding occurred in 42 (5.9%) breasts. The patients were divided into no-bleeding (n\u0026thinsp;=\u0026thinsp;667) and bleeding (n\u0026thinsp;=\u0026thinsp;42) groups, and their clinicopathological characteristics were compared (\u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e). No significant differences were observed between the two groups with respect to age, comorbidities (hypertension, dyslipidemia, or diabetes), use of oral antiplatelet or anticoagulant therapy, coagulation-related parameters (platelet count, PT-INR, APTT) or breast cancer laterality. Variables reflecting the disease extent showed consistent trends between the two groups. Although no significant differences were observed in tumor size, histological type, or intrinsic subtype between the two groups, patients in the bleeding group were significantly less likely to have received NAC (4.7% vs. 25.3%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.01), undergone Ax (19.0% vs. 39.0%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), or have pathological lymph node metastasis (7.1% vs. 29.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Consequently, stage 0\u0026ndash;I disease was more prevalent in the bleeding group (57.1% vs. 14.5%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eRegarding perioperative clinical factors, no significant differences in the operation time or intraoperative blood loss were observed. The surgeon category differed between the groups, with faculty surgeons accounting for a significantly higher proportion of the bleeding group (59.5% vs. 42.2%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04). The duration of postoperative drainage was significantly longer in the bleeding group than in the no-bleeding group (5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7 vs. 3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 days, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Postoperative length of hospital stay also tended to be longer in the bleeding group, although the difference did not reach statistical significance (7.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 vs. 7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 days, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.08).\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComparison of BMI and PMI according to post-surgical bleeding\u003c/h2\u003e \u003cp\u003eWe next compared BMI and PMI between patients with and without post-surgical bleeding. BMI was significantly higher in the bleeding group (26.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7) than in the no-bleeding group (22.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). On the other hand, PMI was significantly lower in the bleeding group (2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69) than in the no-bleeding group (3.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e\u003cb\u003eIncidence of post-surgical bleeding according to BMI and PMI\u003c/b\u003e\u003c/h2\u003e \u003cp\u003eGiven that patients who experienced post-surgical bleeding tended to have a higher BMI and lower PMI, we next compared the incidence of bleeding across BMI- and PMI-defined subgroups. Patients were divided into high and low BMI or PMI groups according to the cutoff values determined by ROC curve analysis for post-surgical bleeding. The cutoff values were 23.7 for BMI (area under the curve [AUC]\u0026thinsp;=\u0026thinsp;0.71; sensitivity/specificity\u0026thinsp;=\u0026thinsp;0.64) and 2.90 for PMI (AUC\u0026thinsp;=\u0026thinsp;0.64; sensitivity/specificity\u0026thinsp;=\u0026thinsp;0.59).\u003c/p\u003e \u003cp\u003eIn the BMI analysis, patients in the BMI-high group exhibited a significantly higher incidence of post-surgical bleeding (10.9%) than those in the BMI-low group (3.1%) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e). Conversely, the PMI-low group demonstrated a significantly higher incidence of bleeding (8.4%) than the PMI-high group (4.1%) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cb\u003eSupplementary Table\u0026nbsp;2\u003c/b\u003e). Taken together, these findings indicate that a high BMI and low PMI are significant risk factors for post-surgical bleeding.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation between preoperative BMI and PMI\u003c/h2\u003e \u003cp\u003eIn our previous study, a moderate positive correlation between BMI and SMI was observed (r\u0026thinsp;=\u0026thinsp;0.54) in a breast cancer cohort [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Hypothesizing that PMI would also positively correlate with BMI, we investigated the correlation between BMI and PMI. We found that PMI showed a weak positive correlation with BMI (r\u0026thinsp;=\u0026thinsp;0.16) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), indicating that PMI and BMI capture different components of body composition and function as independent factors.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eImpact of BMI and PMI as risk factors for post-surgical bleeding\u003c/h2\u003e \u003cp\u003eNext, we explored independent risk factors for postsurgical bleeding using univariate and multivariate analyses. Because BMI and PMI showed a weak correlation (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e), both variables were included in the univariate and multivariate models. Univariate analysis revealed that axillary procedure (none or SLNB) (hazard ratio [HR], 3.19; 95% confidence interval [CI], 1.53\u0026ndash;7.56; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), low PMI (HR, 0.51; 95% CI, 0.31\u0026ndash;0.78; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), and high BMI (HR, 1.12; 95% CI, 1.10\u0026ndash;1.25; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) were significantly associated with post-surgical bleeding (\u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e). In the multivariate logistic regression analysis, axillary procedure (none or SLNB) (HR, 5.07; 95% CI, 2.27\u0026ndash;12.8; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), low PMI (HR, 0.18; 95% CI, 0.09\u0026ndash;0.32; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and high BMI (HR, 1.38; 95% CI, 1.27\u0026ndash;1.52; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) remained significant (\u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e), indicating that both higher BMI and lower PMI independently increase the risk of this complication.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eCombinatorial impact of BMI and PMI as a risk factor for post-surgical bleeding\u003c/h2\u003e \u003cp\u003eAs shown in the preceding analyses, high BMI and low PMI may be independent risk factors for postsurgical bleeding. To evaluate their combined effect, we stratified the patients into four BMI-PMI categories (BMI-low/PMI-high, BMI-low/PMI-low, BMI-high/PMI-high, and BMI-high/PMI-low). The BMI-high/PMI-low group showed the most pronounced susceptibility to bleeding (20.1%), with progressively lower rates observed in the BMI-high/PMI-high (7.4%), BMI-low/PMI-low (4.8%), and BMI-low/PMI-high (1.3%) groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, \u003cb\u003eSupplementary Table\u0026nbsp;3\u003c/b\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that an elevated BMI and reduced PMI were significant risk factors for post-surgical bleeding after mastectomy. Notably, their combined assessment identified patients at an elevated risk of this complication more effectively than either factor alone. To the best of our knowledge, this is the first study to show that the pectoralis major muscle mass may contribute to bleeding risk in patients with breast cancer undergoing mastectomy.\u003c/p\u003e \u003cp\u003eThe primary sources of post-surgical bleeding following mastectomy are likely inadequately sealed vessels on the surface of the pectoralis major muscle, within the subcutaneous fat, or in the axillary region. Since a wider extent of tissue dissection is generally associated with an increased risk of post-surgical bleeding [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], Ax would be expected to confer a higher bleeding risk than SLNB. However, in line with the results of this study, our previous study demonstrated that Ax was associated with a lower risk of post-surgical bleeding than SLNB. This paradoxical result suggests that in patients undergoing mastectomy, post-surgical bleeding is more likely to originate from the surface of the pectoralis major muscle or subcutaneous tissue than from the axillary region. In patients with high BMI, abundant subcutaneous fat may obscure small vessels and hinder meticulous hemostasis, resulting in an increased risk of inadequate ligation and subsequent bleeding. This is consistent with the higher incidence of post-surgical bleeding observed in patients with an elevated BMI in this study. Moreover, patients with a low PMI tend to have an atrophic pectoralis major muscle, which may increase the fragility of the vessels running over the muscle, thereby predisposing them to post-surgical bleeding. Taken together, these findings suggest that excess subcutaneous fat and reduced pectoralis major muscle mass, represented by high BMI and low PMI, are synergistically associated with an increased risk of post-surgical bleeding after mastectomy.\u003c/p\u003e \u003cp\u003eIn our previous study, SMI assessed at the L3 level was not a significant risk factor for post-surgical bleeding when considered alone [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, when SMI was normalized to BMI, the resulting SMI-to-BMI ratio became a robust predictor of post-surgical bleeding, highlighting the importance of relative muscle mass in the context of overall adiposity rather than absolute skeletal muscle quantity. These findings suggested that sarcopenia is insufficient to explain bleeding susceptibility unless accompanied by excess adiposity, a condition conceptually aligned with sarcopenic obesity [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In contrast, in the present study, PMI showed only a very weak correlation with BMI, and a low PMI was independently associated with post-surgical bleeding, even without normalization for BMI. This discrepancy highlights the fundamental differences between global muscle indices and region-specific muscle assessments. While L3-based SMI reflects the overall trunk musculature and requires adjustment for body weight to capture clinically relevant vulnerability, PMI represents the local muscle mass adjacent to the operative field and may directly influence tissue integrity and vulnerability during surgery for breast cancer. Consequently, PMI and BMI function as largely independent risk factors, and their combination identifies patients at particularly high risk of post-surgical bleeding after mastectomy.\u003c/p\u003e \u003cp\u003eInterestingly, the surgeon category was associated with post-surgical bleeding in our cohort, with a higher incidence observed in faculty-performed procedures, as shown in \u003cb\u003eTable\u0026nbsp;1\u003c/b\u003e. This finding appears counterintuitive given that surgical experience is generally associated with improved perioperative outcomes [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Several factors specific to breast surgery may explain these findings. First, mastectomy is a highly standardized procedure with well-established operative steps, routine drain placement, and institutional protocols for postoperative compression and monitoring, which may attenuate the differences attributable to individual techniques. Second, resident operations are typically conducted under the supervision of direct faculty members. Indeed, at our institution, all resident-performed breast surgeries were conducted by a faculty surgeon who served as the first assistant. This mandatory supervision system likely ensures consistent intraoperative hemostatic quality and mitigates differences related to surgeon experience. Consistent with this notion, previous large database analyses have shown that trainee participation in breast surgery does not increase the incidence of early postoperative complications [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Third, faculty surgeons were more likely to be assigned to technically demanding or high-risk cases, including those with a higher BMI. Such case allocations may partially account for the increased risk of bleeding observed in surgeries performed by faculty members. Finally, experience-based effects may become more apparent in technically novel and/or complex approaches such as endoscopic/robotic surgery, where measurable learning curves have been reported [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], rather than in conventional mastectomy. Collectively, these considerations suggest that in routine mastectomy practice, patient-related factors (BMI and PMI) appear to play a more prominent role than operator-related factors in determining post-surgical bleeding risk.\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, this was a retrospective analysis conducted at a single institution, which may be associated with a selection bias. Second, the number of post-surgical bleeding events was relatively small, potentially limiting the statistical power of the multivariable analyses. Third, post-surgical bleeding was defined based on early postoperative clinical criteria, which may not fully capture minor or late-onset bleeding events. Finally, as the study population consisted exclusively of Japanese patients, the generalizability of these findings to other populations remains uncertain. To overcome these limitations, prospective multicenter studies with larger and more diverse cohorts are warranted.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study demonstrates that BMI and PMI are independent predictors of post-surgical bleeding after mastectomy for breast cancer. The preoperative assessment of body composition may help identify patients with a higher risk of bleeding.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eBCS, breast-conserving surgery; BMI, body mass index; SMI, skeletal muscle index; L3, third lumbar vertebral level; CT, computed tomography; SLNB, sentinel lymph node biopsy; Ax, axillary dissection; NAC, neoadjuvant chemotherapy; FEC, fluorouracil–epirubicin–cyclophosphamide; EC, epirubicin–cyclophosphamide; HER2, human epidermal growth factor receptor 2; TN, triple-negative; PT-INR, prothrombin time-international normalized ratio; APTT, activated partial thromboplastin time; ER, estrogen receptor; PgR, progesterone receptor; PMI, pectoralis major muscle mass index; PMA, pectoralis major muscle area; Th2, second thoracic vertebra; ROC, receiver operating characteristic; HR, hazard ratio; CI, confidence interval\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement:\u003c/strong\u003e We would like to thank Editage (www.editage.com) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was not funded by any grant.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting Interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthor Contributions\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRyoko Iji and Takaaki Oba designed the study. Reina Miyazawa,\u0026nbsp;Ayaka Kitazawa, Nami Kiyosawa, Shota Katsuyama, Hiroki Morikawa, Masatsugu Amitani, Tatsunori Chino, Tadafumi Sshimizu, Mayu Ono, Keiko Natori and Toshiharu Kanai collected the clinical data. Ryoko Iji and Takaaki Oba performed the statistical analysis. The draft manuscript was prepared by Ryoko Iji, Takaaki Oba and Ken-ichi Ito. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData Availability\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this work are available from the authors upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e The study was conducted in accordance with the Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013) and approved by the ethics committee of Shinshu University (approval no. 6712).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e Given the retrospective nature of the study using anonymized data, the requirement for written informed consent was waived. An opt-out option was provided via the institutional website.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMiller KD, Nogueira L, Devasia T, Mariotto AB, Yabroff KR, Jemal A, Kramer J, Siegel RL (2022) Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin 72:409\u0026ndash;436\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKummerow KL, Du L, Penson DF, Shyr Y, Hooks MA (2015) Nationwide trends in mastectomy for early-stage breast cancer. JAMA Surg 150:9\u0026ndash;16\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNelson JA, Rubenstein RN, Haglich K, Chu JJ, Yin S, Stern CS, Morrow M, Mehrara BJ, Gemignani ML, Matros E (2022) Analysis of a Trend Reversal in US Lumpectomy Rates From 2005 Through 2017 Using 3 Nationwide Data Sets. JAMA Surg 157:702\u0026ndash;711\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVeronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227\u0026ndash;1232\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Boniface J, Szulkin R, Johansson ALV (2023) Medical and surgical postoperative complications after breast conservation versus mastectomy in older women with breast cancer: Swedish population-based register study of 34 139 women. Br J Surg 110:344\u0026ndash;352\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Hilli Z, Wilkerson A (2021) Breast Surgery: Management of Postoperative Complications Following Operations for Breast Cancer. Surg Clin North Am 101:845\u0026ndash;863\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAleixo GFP, Valente SA, Wei W, Moore HCF (2023) Association of body composition and surgical outcomes in patients with early-stage breast cancer. Breast Cancer Res Treat 202:305\u0026ndash;311\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePastoriza J, McNelis J, Parsikia A, Lewis E, Ward M, Marini CP, Castaldi MT (2021) Predictive Factors for Surgical Site Infections in Patients Undergoing Surgery for Breast Carcinoma. Am Surg 87:68\u0026ndash;76\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarland M, Hsu FC, Clark C, Chiba A, Howard-McNatt M (2018) The impact of obesity on outcomes for patients undergoing mastectomy using the ACS-NSQIP data set. 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BJS Open 4:27\u0026ndash;44\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 and 2 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"breast-cancer-research-and-treatment","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brea","sideBox":"Learn more about [Breast Cancer Research and Treatment](https://www.springer.com/journal/10549)","snPcode":"10549","submissionUrl":"https://submission.nature.com/new-submission/10549/3","title":"Breast Cancer Research and Treatment","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pectoralis major muscle index, Body mass index, Post-surgical bleeding, Mastectomy, Breast cancer","lastPublishedDoi":"10.21203/rs.3.rs-8846876/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8846876/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003ePost-surgical bleeding is a clinically relevant complication after mastectomy. Although high body mass index (BMI) is associated with the risk of this complication, the impact of regional skeletal muscle mass adjacent to the operative field remains unclear. This study aims to evaluate the association between pectoralis major muscle mass and post-surgical bleeding after mastectomy in patients with breast cancer.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed 669 patients who underwent mastectomy between 2015 and 2022, involving a total of 709 breasts. The pectoralis major muscle area was measured using preoperative computed tomography (CT) at the Th2 level, and the pectoralis major muscle index (PMI) was then calculated as the muscle area divided by height squared. We analyzed the association between BMI and PMI, and the incidence of post-surgical bleeding.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003ePost-surgical bleeding occurred in 42 cases (5.9%). Patients who experienced bleeding had significantly higher BMI (26.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7 vs. 22.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and lower PMI (2.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69 vs. 3.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.82, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) than those without bleeding. BMI and PMI were weakly correlated (r\u0026thinsp;=\u0026thinsp;0.16). On multivariate analysis, high BMI (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.27\u0026ndash;1.52, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and low PMI (HR 0.18, 95% CI 0.09\u0026ndash;0.32, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) were independently associated with an increased risk of post-surgical bleeding. Combined stratification demonstrated that patients with a high BMI and low PMI had the highest incidence of bleeding (20.1%), whereas those with a low BMI and high PMI had the lowest risk (1.3%).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eLow PMI and high BMI are independent predictors of post-surgical bleeding after mastectomy. Assessment of regional muscle mass using preoperative CT may enhance perioperative risk stratification in patients with breast cancer.\u003c/p\u003e","manuscriptTitle":"Low pectoralis major muscle mass predicts the risk of post-surgical bleeding after mastectomy in patients with breast cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-26 09:15:00","doi":"10.21203/rs.3.rs-8846876/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-04-12T21:13:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"240567259629270789212590432367401119308","date":"2026-03-23T08:00:00+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-21T02:40:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-11T07:18:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-11T07:18:11+00:00","index":"","fulltext":""},{"type":"submitted","content":"Breast Cancer Research and Treatment","date":"2026-02-11T03:54:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"breast-cancer-research-and-treatment","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"brea","sideBox":"Learn more about [Breast Cancer Research and Treatment](https://www.springer.com/journal/10549)","snPcode":"10549","submissionUrl":"https://submission.nature.com/new-submission/10549/3","title":"Breast Cancer Research and Treatment","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9bbfa89a-a20e-4c0d-be89-19d7a4174c69","owner":[],"postedDate":"March 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-26T09:15:00+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-26 09:15:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8846876","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8846876","identity":"rs-8846876","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}