Front. Oncol. Frontiers in Oncology Front. Oncol. 2234-943X Frontiers Media S.A. 10.3389/fonc.2025.1662132 Oncology Systematic Review Primary breast leiomyosarcoma: prognostic factors and treatment outcomes – a systematic review and case report (1969–2023) Guo Rui 1 † Zhang Weiwei 1 * † Ji Xingli 2 Liu Xiaohu 3 He Lang 1 * 1 Department of Oncology, Cancer Prevention and Treatment Institute of Chengdu, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China 2 Department of Pathology, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China 3 Department of Imaging, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, China

Edited by: Mustafa Cem Algin, TC Saglik Bakanligi Eskisehir Sehir Hastanesi, Türkiye

Reviewed by: Narges Bazgir, Shahid Beheshti University, Iran

Elif Berna Koksoy, Ankara University, Türkiye

*Correspondence: Weiwei Zhang, zww89@126.com; Lang He, helang126@outlook.com

†These authors have contributed equally to this work

 30 10 2025 2025 15 1662132 10 07 2025 14 10 2025 Copyright © 2025 Guo, Zhang, Ji, Liu and He. 2025 Guo, Zhang, Ji, Liu and He

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 Objective

This study aims to investigate the prognostic factors and treatment outcomes of primary breast leiomyosarcoma (PBL). We present a contemporary case of postoperative recurrence and metastasis, and conduct a systematic review to comprehensively analyze all reported cases over the past 54 years.

 Method

We describe a 48-year-old female with primary breast leiomyosarcoma managed with multimodal therapy, including surgery, chemotherapy, radiotherapy, and immunotherapy. Additionally, a systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We searched multiple electronic databases for studies on PBL published between 1969 and 2023. Patient demographics, clinical characteristics, and treatment strategies were extracted from the eligible studies. Kaplan-Meier survival analysis was employed to assess overall survival (OS), and Cox proportional hazards regression models were used to evaluate prognostic factors, including age, tumor size, and treatment approach.

 Result

The systematic search identified 98 eligible studies, which collectively reported on 106 patients with PBL. The PRISMA 2020 flow diagram illustrated the study selection process. Among the patients, 86.8% were female, and 50.9% of tumors originated in the left breast. The mean pretreatment tumor diameter was 6.38 ± 4.98 cm. Surgical intervention was performed in 88.1% of cases, predominantly mastectomy. Survival analysis revealed a median OS of 18 months. Subgroup analysis demonstrated significantly shorter OS in patients aged ≤37 years at diagnosis or with tumors >7 cm (P<0.05). Multivariate Cox regression identified younger age at diagnosis as an independent predictor of poor prognosis (HR: 4.514, 95% CI: 1.146-17.784, P = 0.031).

 Conclusion

Surgical resection remains the cornerstone of treatment for PBL. Our findings, derived from a PRISMA-guided systematic review, highlight younger age at diagnosis as a significant adverse prognostic factor, underscoring the need for tailored therapeutic strategies for this high-risk subgroup.

 breast leiomyosarcoma breast sarcoma prognosis overall survival tumor size section-in-acceptance Breast Cancer Introduction

Primary breast leiomyosarcoma, first described by Schmidt in 1887, is an exceedingly rare malignant mesenchymal tumor of the breast (1, 2). Breast sarcomas collectively account for approximately 1% of all breast malignancies, encompassing various histological subtypes including leiomyosarcoma, fibrosarcoma, angiosarcoma, and lymphosarcoma (3, 4). As a distinct entity, primary breast leiomyosarcoma predominantly affects postmenopausal women and demonstrates an intermediate prognosis - generally more favorable than other breast sarcomas but less favorable than epithelial breast carcinomas (5, 6). Despite numerous case reports in the literature, no standardized treatment protocol has been established for breast leiomyosarcoma.

Notably, while multiple case reports and limited series analyses have been published until 2024, a comprehensive systematic review incorporating survival analysis and prognostic factor evaluation of all reported cases over the past 54 years remains lacking. Therefore, we shared the diagnosis and treatment process of a 48-year-old female case of postoperative recurrence and metastasis of primary breast leiomyosarcoma, and conducted a literature review and secondary analysis of all case reports on primary breast leiomyosarcoma in the past 54 years.

 Materials and methods Study design

Given the absence of standardized treatment protocols for primary breast leiomyosarcoma, current management strategies are largely extrapolated from sarcoma therapies in other anatomical sites. To systematically characterize primary breast leiomyosarcoma, features and treatment outcomes, we conducted a comprehensive literature review of studies published between 1969 and 2023. Eligible publications in English and Chinese were identified through database searches, rigorously screened using predefined inclusion/exclusion criteria, and analyzed to evaluate associations between age, tumor size, and overall survival (OS).

 Eligibility criteria and research question

This systematic review was conducted to address the following question: “What are the prognostic factors and treatment outcomes for patients with primary breast leiomyosarcoma?” The eligibility criteria were structured using the PICOS framework: (1) Population: Patients of any age or gender with a histologically confirmed primary breast leiomyosarcoma. (2) Exposure: The diagnosis of primary breast leiomyosarcoma. (3) Comparators: Not applicable. (4) Outcomes: The primary outcome was overall survival (OS), defined as the time from diagnosis to death from any cause. Secondary outcomes included patient demographics, tumor characteristics (size, location), treatment details (surgery, chemotherapy, radiotherapy), and recurrence. (5) Study Designs: All published case reports, case series, and observational studies reporting on primary breast leiomyosarcoma were eligible for inclusion.

 Search strategy

Two independent reviewers (R.G. and W.Z.) performed a systematic search of PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Database for studies published from inception until December 31, 2023. The search strategy utilized the key terms “breast” AND “leiomyosarcoma” across all fields. The overall search strategy was (1) breast (all fields) and (2) leiomyosarcoma (all fields). Searches in electronic databases combined the terms 1 and 2. The complete, database-specific search strategies, including all keywords and Boolean operators, are provided in Supplementary File 1 .

 Study selection criteria

The study selection process was conducted independently by the same two reviewers (R.G. and W.Z.). The reviewers independently screened the titles and abstracts of all retrieved records against the eligibility criteria. Studies that clearly did not meet the criteria were excluded. The full texts of all records that appeared relevant or whose eligibility was uncertain based on the title/abstract were retrieved. The same two reviewers then independently assessed these full-text articles for final inclusion. The following exclusion criteria were applied: (i) cases without a pathologically confirmed diagnosis of primary breast leiomyosarcoma; (ii) cases with missing critical information on age, tumor size, or survival outcomes; (iii) literature for which the full text was unavailable.

At both screening stages, any disagreement between the two reviewers regarding the inclusion or exclusion of a study was first addressed through discussion. If a consensus could not be reached, the final decision was made by a third senior reviewer (L.H.).

 Data extraction and management

To ensure the accuracy and consistency of data collection, a standardized data extraction form was developed a priori. The following data were extracted from each included study: first author, publication year, patient age and sex, tumor size and location, treatment modalities (surgery, chemotherapy, radiotherapy), and survival outcomes (overall survival (OS) time, status).

The data extraction was performed independently by two reviewers (R.G. and W.Z.) using this standardized form. To minimize errors and confirm data accuracy, the two reviewers cross-checked each other’s completed extraction forms. Any discrepancies or uncertainties in the extracted data were identified and then resolved by jointly reviewing the original source document. In cases where critical data (e.g., specific treatment details or exact survival times) were ambiguous or missing from the published report, we attempted to contact the corresponding authors via email to obtain clarification. No automation tools were used in the data collection process.

 Outcomes

The primary outcome of this systematic review was OS, defined as the time interval from the date of pathological diagnosis to death from any cause or the date of last follow-up for surviving patients. Secondary outcomes included key tumor characteristics (size, location, lymph node or vascular invasion status) and primary treatment modalities (surgery, chemotherapy, radiotherapy).

Regarding data completeness for each outcome, we sought the most definitive result available in each study. For OS, this meant extracting the final survival status at the longest reported follow-up time for each case, rather than survival rates at multiple pre-specified time points, due to inconsistent reporting across the included literature.

 Risk of bias assessment

The methodological quality of the included case reports and case series was assessed using the respective critical appraisal tools from the Joanna Briggs Institute (JBI). Two reviewers (X.J. and X.L.) independently conducted the assessments. If a consensus could not be achieved, a third senior reviewer (L.H.) was consulted to make the final decision. Given the retrospective and descriptive nature of the majority of included studies, which often lacked detailed reporting on specific criteria (e.g., unambiguous description of diagnostic criteria or follow-up schedules), the overall quality was variable. The primary aim of this assessment was to transparently characterize the strengths and limitations of the available evidence base rather than to exclude studies.

 Statistical analysis

Demographic and clinical characteristics of the study cohort, including mean age and tumor diameter, were analyzed using descriptive statistics. Continuous variables are presented as mean ± standard deviation. To evaluate survival outcomes, Kaplan-Meier (KM) analysis was performed to estimate median OS in all eligible patients. Survival distributions between subgroups were compared using log-rank tests. Univariate and multivariate Cox proportional hazards regression models were employed to assess the prognostic significance of key variables, including tumor characteristics (size and location), demographic factors (age and gender) and treatment modalities. These analyses were conducted to identify independent predictors of survival outcomes in breast leiomyosarcoma patients. All statistical tests were two-sided, with P < 0.05 considered statistically significant.

 Results Case presentation

A 48-year-old woman presented with a 2×3 cm right breast mass discovered during routine physical examination. Following simple lumpectomy at a local hospital, pathological examination confirmed primary breast leiomyosarcoma ( Figure 1 ), which was subsequently verified by our institutional review. The patient received no adjuvant therapy postoperatively. Two years later, she developed progressive lower back pain refractory to non-steroidal anti-inflammatory drugs (NSAIDs), accompanied by lumbar stiffness and ambulatory difficulty. Initial lumbar magnetic resonance imaging (MRI) demonstrated compression fractures without definitive intervention, and her symptoms progressively worsened to complete mobility impairment.

CT images after percutaneous kyphoplasty (PKP) of patient. (A, B). The horizontal plane CT image of patient after PKP. (C). The coronal CT images of patient after PKP. (D) The sagittal CT images of patient after PKP.

CT scan images display axial and sagittal views of a spinal and abdominal region with contrast highlighting certain areas. Panels a and b show horizontal slices, whereas c and d depict vertical sections. Each panel is marked with letters a through d.

Ten months following symptom onset, repeat MRI revealed multiple thoracolumbar pathological fractures with posterior element destruction. The patient was subsequently referred to our orthopedic service with significant functional impairment (Eastern Cooperative Oncology Group Performance Status (ECOG) score is 3, bedbound status). She underwent C-arm guided percutaneous kyphoplasty (PKP) with biopsy of lumbar vertebrae 2 and 4 under local anesthesia, which demonstrated extensive osteolytic destruction involving the laminae, pedicles, and vertebral bodies. Notably, lumbar vertebrae 3 showed near-complete bony obliteration ( Figure 2 ). Histopathological analysis confirmed metastatic breast leiomyosarcoma, supported by characteristic immunohistochemical profile: positive for smooth muscle actin (SMA), cluster of differentiation (CD) 34, and CD10, negative for Desmin and CD117, and with a low proliferative index (Ki-67 5-10%).

HE and immunohistochemical staining results of tumor tissue. (a) HE staining results show the tumor cells were spindle-shaped, infiltrative, and interlaced, with cigar-like nuclei, eosinophilic cytoplasm, perinuclear vacuoles, and has moderately anisotropic, nuclear schizophrenic and atypical nuclear schizophrenic images. (b) The tumor cells were positive for CD34 (×200). (c) The tumor cells were positive for CD10 (×200). (d) The tumor cells were positive for SMA (×200).

Panel of four histopathological images labeled a to d. Image a shows densely packed spindle-shaped cells with a pinkish hue, indicating haematoxylin and eosin staining. Image b displays loosely arranged fibrous tissue with sparse cellularity. Image c features connective tissue with dark-stained thick fibrous bands. Image d shows densely packed fibrous tissue with increased staining intensity, indicating higher cell density.

The patient came to our department for further treatment after the surgery. CT scan indicates that the patient only has bone metastasis and no recurrence or metastasis in other areas. Considering the extremely high risk of paraplegia, after sufficient communication with the patient and their family, IMRT technology was used to complete lumbar palliative radiation therapy. The radiation dose prescription was 95% DT P-GTVm1 = 6000cGy/30F/200cGy, P-GTVm2 = 4000cGy/20F/200cGy, P-CTV=3600cGy/20F/180cGy. After radiotherapy, 6 cycles of pembrolizumab combined with albumin bound paclitaxel and carboplatin were performed. The specific usage was pembrolizumab 200mg, albumin paclitaxel 260mg/m2, carboplatin AUC = 5 on day 1 every three weeks. After 6 cycles of treatment, the patient chose pembrolizumab immune maintenance therapy, administered every 3 weeks at a dose of 200mg each time, while also receiving bisphosphate to prevent bone related events. After treatment, the patient did not experience any further lumbar pain and returned to normal daily activities. The ECOG score was 1 point.

One year later, the patient began to experience back pain, which gradually worsened. Complete CT and MRI examinations revealed metastatic tumors in multiple vertebral bodies and some ribs of the thoracic and lumbar vertebrae, of which the thoracic 10 vertebral bodies were metastatic and invaded the spinal cord. Considering the progression of the tumor, palliative radiotherapy for the thoracic 10 vertebrae was performed at a dose of 95% DT P-GTVm=4500cGy/15F/300cGy, P-CTV=3000cGy/15F/200cGy. At the same time, 6 cycles of pembrolizumab combined with systemic intravenous chemotherapy were performed again. The chemotherapy regimen was pembrolizumab (200 mg on day 1), epirubicin hydrochloride (70 mg/m2 on day 1), ifosfamide (2000 mg/m2/day on day 1 to day 5), and mesna europrotection (400 mg/m2/day on day 1 to day 5). At present, the patient’s living condition is good, and as of the last follow-up, the total survival time of the patient is as long as 4 years.

 Study selection flowchart

After the screening process ( Figure 3 ), 98 papers were deemed to meet our system evaluation criteria. Table 1 lists the data of 106 cases in 98 articles. However, through further information extraction and screening of the literature, a total of 98 patients were included in subsequent survival analysis and Cox multivariate risk analysis.

Paper selection flowchart.

Flowchart of a study selection process. Under “Identification,” 577 records are identified from PubMed and 37 from the China National Knowledge Infrastructure. After removing duplicates, 106 records remain. All records are screened, with 8 excluded for lacking survival data. “Eligibility” results in 98 studies included in the analysis.

The clinical data of 106 cases.

No. Author/s (year of publication) Age (years) Gender Tumor location Tumor size (cm) Mitoses/10 HPF Lymph node/ vascular invasion Treatment Metastasis Outcome and follow-up
1 Crocker (1969) (7) 51 M R 5 Common NA RM NET Alive, 7 months
2 Haagensen (1971) (8) 77 F L 8 Frequent NA SM NET Alive, 14 years
3 Pardo-Mind 'an(1974) (9) 49 F L 7 16 Yes SM NET Alive, 6 months
4 Barnes and Pietruszka (1977) (10) 55 F L 3 10 NA SM NET Died, 4 years and 4 months later due to basilar artery thrombosis
5 Hernandez (1978) (11) 53 M L 4 15 NO MRM NET Alive, 14 months
6 Chen, Kuo and Hoffmann (1981) (12) 59 F L 5.6 3 NO SM Hepatic metastasis Alive, 15 years
7 Callery, Rosen and Kinne (1984) (13) 56 F NA 2 NA NA SM NET Alive, 39 months
8 Callery, Rosen and Kinne (1984) (13) 54 F NA 3 NA NA SM NET Alive, 53 months
9 Gobardhan (1984) (14) 50 F L 9 5 NA MRM NET Alive, 2 years
10 Yatsuka et al. (1984) (15) 56 F L 1.5 21 NO RM NET Alive, 4 years 7 months
11 Nielsen (1984) (16) 24 F R 1.5 2 NO Excision Local recurrence and systemic recurrence (brain, skin, thyroid, kidney) Died, 20 years later
12 Yamashina (1987) (17) 62 F L 1 24 NA RM NET Alive, 2 years 2months
13 Arista-Nasr et al. (1989) (18) 50 F R 4.5 4 NA Excision Local recurrence Alive, 6 years
14 Alessi and Sala (1992) (8) 62 M R NA 1 NA Excision Local recurrence Alive, 6 years
15 Lonsdale and Widdison (1992) (19) 60 F L 2 10 NO SM Local recurrence Alive, 3 months
16 Parham et al. (1992) (20) 52 F L 3 29 NA SM Local and systemicrecurrence (brain, lung) Alive, 6 months
17 Waterworth et al. (1992) (21) 58 F L 4 10 NO Excision NET Alive, 1 year
18 Wei (22) 36 F L 4 NA NA MRM Systemic recurrence(brain, bone), left breast Died, 14 months later
19 Boscaino et al. (1994) (23) 56 F R 2.5 2 NO MRM Local recurrence Alive, 9 years
20 Boscaino et al. (1994) (23) 45 F L 2.2 2 NO WLE Local recurrence Alive, 40 months
21 Falconieri et al. (1997) (24) 83 F R 6x5x5.5 20 NO MRM NET Alive, 10 months
22 Falconieri et al. (1997) (24) 86 F R 8x7x6 11 NO SM NET Alive, 8 months
23 U ğras , et al. (1997) (25) 47 F R 2 3 NO Excision + SM NET Alive, 18 months
24 Gonzalez-Palacios F(1998) (26) 62 F L 3 10 NA SM NET Alive, 17 years
25 Gupta et al. (2000) (27) 80 F L 7x5 8 NO MRM NET Alive, 2 years
26 Hussien et al. (2001) (8) 49 F R 2 ≤12 NO MRM NET Alive, 18 months
27 Szekely et al. (2001) (28) 73 F R 4.5 20-22 NO MRM NET Alive, 1 year
28 Kusama et al. (2002) (29) 55 F L 1 10 NO MRM Local recurrence, systemic metastasis (lung, bone) Alive, 4 years 8 months
29 Shinto et al. (2002) (30) 59 F L 12 19 NO MRM Local and systemicrecurrence (lung) Alive, 8 months
30 Liang et al. (2003) (31) 25 F L 4 5 NA WLE NET Alive, 32 months
31 Markaki et al. (2003) (32) 42 F R 10x4x14 50 NO MRM NET Alive, 3 years
32 Markaki et al. (2003) (32) 65 F L 5x1 10 NA Excision NET Alive, 18 months
33 Jun Wei et al. (2003) (33) 52 F R 1.5 22 NA Excision NET Alive, 3 months
34 Adem (2004) (34) 67 F NA 2 NA NA Excision Local and systemic recurrence Died, 7 months later
35 Adem (2004) (34) 55 F NA 4 NA NA Mastectomy Systemic recurrence Died, 77 months later
36 Lee et al. (2004) (35) 44 F NA 3 6-12 NA SM NET Alive, 13 months
37 Lee et al. (2004) (35) 52 F NA 4.5 6-12 NA SM NET Alive,17 months
38 Munitiz et al. (2004) (36) 58 F R 4 14 NO MRM NET Alive,12 months
39 Stafyla, Gauvin and Farley (2004) (37) 53 F L 23 NA NO MRM NET Alive, 2 years
40 Jayaram, Jayalakshmi and Yip (2005) (38) 55 F R 12 40 NO MRM Local recurrence Alive, 2 months
41 Gupta (2007) (39) 37 F R 8x6 15 NO WLE NET Alive, 36 months
42 Ende (2007) (8) 48 F L 1.2 0 NA Excision NA NA
43 De la Pena and Wapnir (2008) (40) 50 F L 3.5x1.4x2.8 Few NA SM NET Alive, 11 months
44 Wong et al. (2008) (41) 52 F L 1.5x1.10.7 7 NA SM NET Alive, 4days
45 Cobanoglu et al. (2009) (42) 64 F L 3.6 ≤12 NO MRM NET Alive, 22 months
46 Boehm et al. (2010) (43) 62 M R 4.6x3.5 4 NA MRM NET Alive, 24 months
47 Kamio (2010) (43) 46 F L 0.5 2-8 NA SM NET Alive, 8 years 4 months
48 Masannat Y et al. (2010) (43) 59 M R 1.8x1.3 NA NA SM NET Alive, 26 months
49 Sandhya et al. (2010) (43) 54 F L 7x7 6 NO MRM NET Alive, 1 year
50 Fujita et al. (2011) (43) 18 F R 7.2 10 NO SM NET Alive, 5 years
51 Oktay and Fikret (2011) (43) 44 F L 3.5 Few NA Excision NET Alive, 12 months
52 Nagao et al. (2011) (8) 61 F R 3 >10 NA WLE NET Alive, 18 months
53 Karabulut, Akkaya and Moray (2012) (43) 48 F R 10x9x6 Frequent NO MRM NET Alive, 1 month
54 Rane, Batra and Saikia (2012) (43) 19 F L 8 20-25 NA Excision NET Alive, 3 years
55 Pai and Yoon (2013) (43) 46 F L 7x6x6.5 >10 NA MRM Lung Alive, 3 months
56 Yener and Aksoy (2013) (43) 44 F L 3.5 Few NA Lumpectomy NET Alive,12 months
57 Amaadour et al. (2013) (43) 44 F R 9.2x7.6x6 6 NA Palliative CT lung and abdominal wall Died, 1 month later
58 Basset et al. (2014) (43) 20 F L 3 High NO Excision + MRM NA NA
59 Guedes et al. (2014) (8) 46 F R 1.6x1 3 NA Excision NET Alive, 1 year
60 Agrawal, Garg and Pandey (2015) (8) 40 F R 9x9x8 Frequent YES MRM NET Alive, 1 year
61 Agrawal, Garg and Pandey (2015) (8) 70 F L 8x7x6 NA NO MRM NET Alive, 1 year
62 Sokolovskaya et al. (2014) (43) 58 F R 15x9x13 NA NA MRM Multiple bone and lung Alive, 2 years
63 Kim et al. (2015) (43) 51 F R 4x3x4 15 NA Excision NET Alive, 5 years
64 Tajima, Koda and Fukayama (2015) (43) 50 F L 4.8x4.5x4.2 6 NO MRM NET Alive, 6 months
65 M’rabet et al. (2017) (43) 40 F L 6 NA NO MRM + RT NET Alive, 8 years
66 Arsalane et al. (2017) (8) 68 M R 8x9 9-10 NO MRM NET Alive, 9 months
67 Testori et al. (2017) (4) 62 F L 0.3x0.15 Up to 5 NO Breast conservative surgery NA NA
68 Singh, Sharma and Goyal (2017) (44) 48 F R 16x10 Numerous NA MRM + RT + CT NET Alive
69 Lee and Lee (2017) (43) 49 F L 6x8 ≤18 NA Palliative mastectomy and CT Lung Died 4 months later due to sudden steep decrease in blood pressure
70 Villegas et al. (2018) (8) 48 M L 8x5 NA NO SM NET Alive, 1 month
71 Amberger et al. (2018) (43) 20 F L 3 30 NO Excision + MRM Lung Alive, 3 years
72 Ilyas et al. (2020) (8) 52 F L 6 2-50 YES SM NET Alive, 1 year
73 Liu et al. (2020) (8) 28 F L 1.6x0.9 10 NA WLE NET Alive, 1 year
74 Kumar et al. (2020) (8) 53 F R 8x6 Frequent NA WLE Systemic recurrence (lung, renal, and skeletal) NA
75 Horton et al. (2020) (8) 61 F R 1.6 NA NO WLE NA NA
76 Bürger et al. (2020) (8) 54 F R 3 Up to 3 NO Breast conservative surgery NET Alive, 24 months
77 Ely Cheikh et al. (2021) (8) 65 M RL 7 15 NA L: WLE R:SM + RT NET Alive, 11 months
78 Rina Masadah (2023) (8) 30 F L 12x8 >10 NO WLE NET Alive, 8 months
79 Yan cunli (2015) (45) 27 F R 4x2 NA NO SM+CT NET Alive, 12 months
80 Hong jiafan (2013) (46) 65 M R 2x1.8x1.5 >5 NO RM NET Alive, 3months
81 Yan Juan (2014) (47) 42 F L 7x7x7 0 NO SM NET Alive, 12months
82 Xiao Mingzhen (2013) (48) 29 F R 7x6x4 3 NO SM NET Aline 5months
83 Wang Na (2012) (49) 39 F R 20x20x20 >5 NO SM NET Alive, 24 months
84 Chen kaixing (1995) (2) 55 M R 5x4x3 >10 NO MRM NA Dead, 5months later
85 Bao luping (2003) (50) 57 M R 4x3.5x3 >5 NO SM+RT NET Alive, 3 years
86 Zhang Jian (2010) (51) 73 M L 3.5x3x3 3 NO SM Systemic recurrence Dead, 7 years later
87 Jiang xiaojun (2006) (52) 58 F R 7x6x5 NA NA SM NA NA
88 Liu Xiaojun (2002) (53) 50 M L 18x15x9 1.6 NO SM+RT NA Alive, 12 months
89 Yan Peng (2005) (54) 73 M L 3.5x3 NA NO SM NET Alive, 7 years
90 Yan Peng (2005) (54) 48 F L 15x15 NA NO SM Systemic recurrence (lung) Dead, 1 year later
91 XuTian wen 1999 (55) 40 F R 4x3.5x3 6 NA RM NET Alive, 8 years
92 Wu Tianhui (2002) (56) 38 F R 22x22x12 >10 NO RM NET Alive, 6 months
93 Wu Tianhui (2002) (56) 25 F L 20x20x18 >30 NO RM NET Alive, 1 year
94 Chen Yaokun (2001) (57) 44 F R 15x12x10 NA NO SM+RT Local and systemicrecurrence (lung) Dead, 52 months later
95 Chen Yaokun (2001) (57) 34 F R 12x10x10 NA NO RM NET Alive, 12 years
96 Zhang Renya 1994 (58) 45 F L 2.5x2x1.5 >5 NO SM NET Aline 6 months
97 Wu peijin 1995 (59) 26 F L 8x6x5 NA NO SM+CT Systemic recurrence Dead, 48 months later
98 Wang Jin (2013) (60) 42 F L 2x1.2x1 4 NO WLE+CT NET Alive, 11 years
99 Wu Yongjun (1996) (61) 49 F R 6x5.x3.5 >10 NO SM NET NA
100 Gu Huaping (2005) (62) 54 F R 7.5x1.2x6 >10 NO SM NET Alive 10 months
101 Samenova (2023) (63) 45 F R 10.5 NA Axillary lymph nodes Excision +CT NET Alive, 5 years
102 Sethi (2024) (64) 37 F L 17x17x8 NA NA SM+CT Local recurrence Dead, 3 months later
103 Catarina Félix (2018) (65) 48 F R 5.5x4.3.5 NA NO Palliative care Local and systemic recurrence (liver, gallbladder, and pancreatic) Alive, 6 years
104 Miyazaki C (2019) (66) 52 F L 10 10 Several ipsilateral axillary lymph nodes Neoadjuvant CT +SM NET Alive, 18 months
105 Galama (2021) (67) 87 F L 8x4.4 NA NO SM+RT NET Alive, 20 months
106 Miroslav Lesar (2003) (68) 62 F L NA NA NA RM+RT NA NA

cm, centimeter; CT, chemotherapy; F, female; HPF, high-power fields; L, left; M, male; MRM, modified radical mastectomy; NA, not available; NET: No evidence of tumor; R, right; RM, radical mastectomy; SM, simple mastectomy; RT, radiotherapy; WLE, wide local excision.

 Baseline characteristics of breast leiomyosarcoma patients

The clinical characteristics of 106 cases are listed in Table 2 . The average age of the patients was 50.9 ± 14.4 years old, ranging from 18–87 years. There were 92 female cases, accounting for 86.8% of patients and the male cases accounted for 13.2%. 50.9% of patients had their primary tumor located on the left side. The average size of the primary tumor was 6.38 ± 4.98 cm. At the initial diagnosis, most patients (55.7%) have no lymph node or vascular invasion. Surgical treatment is the main treatment method for patients with primary fibrosarcoma of the breast, accounting for a high proportion 98.1%, including wide local excision (WLE), radical mastectomy (RM), simple mastectomy (SM) and modified radical mastectomy (MRM). The mean overall survival was about 34.53 months.

The clinical characteristics of 106 cases.

Characteristics n (%)
Age (mean ± SD, years) 50.9 ± 14.4
Gender
 Male 14(13.2%)
 Female 92(86.8%)
Tumor location
 Left breast 54(50.9%)
 Right breast 45(42.5%)
 Left and right breast 1(0.9%)
 Not mentioned 6(5.7%)
Tumor diameter (mean ± SD, cm) 6.38 ± 4.98
Lymph node/Vascular invasion
 Yes 5(4.7%)
 No 59(55.7%)
 Not mentioned 42(39.6%)
Treatment
 Surgery 89(84.0%)
 No surgery 2(1.9%)
Surgery combined with radiotherapy and/or chemotherapy 15(14.1%)
Distant metastasis
 Yes 18(17.0%)
 No 80(75.5%)
 Not mentioned 8(7.5%)
Overall survival (mean ± SD, months) 34.53 ± 41.49
Survival outcomes

A total of 98 patients were included in the OS analysis ( Figure 3 ). The clinical characteristics of 98 cases are listed in Table 3 . There were 84 female cases, accounting for 85.7% of patients and the male cases accounted for 14.3%. 51.0% of patients had their primary tumor located on the left side. Similarly, Surgical treatment is the main treatment method for primary breast fibrosarcoma patients.

Clinical characteristics and cox multivariate regression analysis of 98 cases.

Characteristics n (%) HR (95%CI) P
Tumor location 1.070 (0.425-2.693) 0.886
 Right 39(39.8%)
 Left 50(51.0%)
 Right + Left 1(1.0%)
 NA 8(8.2%)
Gender 1.286 (0.151-10.979) 0.818
 Female 84(85.7%)
 Male 14(14.3%)
Age (years) 0.301 (0.088-1.032) 0.056
 ≤37 15(15.3%)
 >37 83(84.7%)
Tumor diameter 4.514 (1.146-17.784) 0.031
 ≤7cm 75(76.5%)
 >7cm 22(22.4%)
 NA 1(1.1%)
Treatment 1.134 (0.869-1.479) 0.355
 SM 28(28.6%)
 MRM 25(25.5%)
 Excision 13(13.3%)
 RM 7(7.1%)
 CT 1(1.0%)
 Surgery combined with RT and/or CT 14(14.3%)
 Simple tumor resection 4(4.1%)
 WLE 6(6.1%)

CT, chemotherapy; NA, not available; RM, radical mastectomy; RT, radiotherapy; SM, simple mastectomy; WLE, extensive local excision.

In order to conduct survival and Cox multivariate analysis, we use the ROC curve to calculate the cutoff values for age and the maximum diameter of the tumor. The results showed that the cutoff value for age was 37 years, with an area under the curve (AUC) of 0.610 and a 95% confidence interval of 0.429-0.729. The sensitivity and specificity are 0.667 and 0.86, respectively. The cutoff value for the maximum diameter of the tumor was 7cm, with an AUC of 0.554 and a 95% confidence interval of 0.360-0.744 ( Figure 4 ). The sensitivity and specificity are 0.5 and 0.318, respectively.

ROC curves for age (a) and tumor diameter (b) in 98 patients.

Two Receiver Operating Characteristic (ROC) curves are shown. Chart a: Area Under Curve (AUC) is 0.610 with a 95% confidence interval of 0.429 to 0.729 and a cutoff value of 37. Chart b: AUC is 0.554 with a 95% confidence interval of 0.36 to 0.744 and a cutoff value of 7.0 centimeters. Both charts plot sensitivity versus 1-specificity with a diagonal reference line.

KM survival indicated that the median OS of these patients was 18.0 months ( Figure 5 ). In subgroup analysis, patients with age ≤ 37 years at initial diagnosis or tumor diameter >7 cm before treatment had a shorter OS, and the differences were statistically significant.

The survival curve of overall survival in patients with breast leiomyosarcoma (a), as well as the comparison of overall survival between different ages (b) and tumor diameters (c).

Three Kaplan-Meier survival curves labeled a, b, and c, showing overall survival over time in months. Graph a depicts one curve. Graph b compares survival based on age group with a p-value of 0.049. Graph c contrasts survival based on tumor diameter with a p-value of 0.023. Each graph uses lines and markers for censored data points, with legends indicating group categories. Prognostic factors from Cox regression

Cox proportional hazards univariate regression analysis consisted of data on tumor diameter, tumor location, patient age, gender and treatment method in 98 patients ( Table 3 ). The results showed that the tumor diameter ≤ 7 cm could significantly improve the prognosis of patients with breast leiomyosarcoma (HR 4.514, 95% CI 1.146-17.784, P = 0.031).

Although there were differences in OS between subgroups aged over 37 and under 37 years, there was no statistically significant difference between age and OS in multivariate analysis (HR 0.301, 95% CI 0.088-1.032, P = 0.056). Whereas, the patient gender (HR 1.286, 95% CI 0.151-10.979, P = 0.818), tumor location (HR 1.070, 95% CI 0.425-2.693, P = 0.886) and treatment method (HR 1.134, 95% CI 0.869-1.479, P = 0.355) did not have a significant effect on the OS of breast leiomyosarcoma.

 Discussion

Breast sarcoma is a rare non-epithelial malignant tumor originating from the mesenchymal tissue of the breast, with approximately 4.6 new cases per million women per year, accounting for less than 1% of all breast malignancies (69, 70). Same with other soft tissue sarcomas, primary breast sarcomas are associated with genetic disorders such as familial adenomatous polyposis and neurofibromatosis type 1 (71). Risk factors include a history of radiotherapy, chronic lymphoedema, vinyl chloride exposure and Epstein-Barr virus (EBV) infection (72). Leiomyosarcomas are rare one of the subtypes to which it belongs, and its exact origin is unclear. It may develop from mesenchymal cells or smooth muscle cells within blood vessels and is most likely to occur in the vascular and muscular tissues of this anatomical region near the areola (1).

The clinical presentation of breast leiomyosarcoma is often a slow-growing large palpable mass, painless, firm, and lobulated, typically found in postmenopausal women (3). There is a tendency for skin and muscle invasion, but areola changes and nipple discharge are relatively rare (6). It is difficult to distinguish from other breast tumors in clinical practice because physical examination and imaging results are often similar to other malignant tumors (43), and are often mistaken for benign causes (lobular tumors and fibroadenomas) (8), and the diagnosis can only be finally confirmed through histological examination and immunohistochemical analysis after biopsy. Histopathology showed marked cellular heterogeneity, atypical mitoses, vascular invasion and necrosis (1). Immunohistochemistry demonstrated that leiomyosarcoma staining positive for desmin, smooth muscle actin and vimentin, whereas it was negative for epithelial markers, cytokeratin and S-100 (43, 73, 74).

Currently, there are insufficient guidelines for the treatment of breast leiomyosarcoma, probably due to the rarity of the disease in this location. As a result, the diagnostic and therapeutic approaches to this type of tumor are highly heterogeneous and require more specific treatment strategies and guidelines (43, 75). Because of the high rate of local recurrence, surgery with adequate resection margins is the only potential treatment for patients with sarcomas. A previous study showed that for optimal efficacy, a minimum negative margin of 3 cm should be achieved; however, a 2 cm margin can be used for breast protection (76). Several studies have reported metastatic spread to lungs, liver and bone, with lymph node involvement being extremely rare (5, 43, 66).

Our study also confirms that there are very few patients with primary breast leiomyosarcoma who are initially diagnosed with lymph node metastasis or vascular invasion. Routine lymph node dissection and sentinel lymph node biopsy is not recommended as it has no impact on patient survival (77). However, biopsy should be performed if lymph node metastasis is suspected on imaging. After surgical resection, radiotherapy is recommended for local control. Adjuvant radiotherapy after breast-conserving mastectomy has been shown to improve disease-free survival and local control of recurrence, especially if resection margins are inadequate (72). Chemotherapy may be indicated for tumors larger than 5 cm, high-grade tumors or advanced cancers (8).

Research suggests that while some patients with leiomyosarcoma (LMS) may benefit from immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors like nivolumab and pembrolizumab) (78), histological subtype analyses reveal that LMS has the lowest response rates compared to subtypes such as alveolar soft part sarcoma and undifferentiated pleomorphic sarcoma, which show the highest (78). Studies on combining these agents with chemotherapy (e.g., doxorubicin, dacarbazine) or radiotherapy in advanced LMS have demonstrated limited but promising clinical activity, with efficacy potentially dependent on the tumor’s immune microenvironment characteristics (79). It is hypothesized that by modulating this microenvironment, immunotherapy may convert immunologically “cold” tumors into “hot” ones, thereby promoting immune cell infiltration. Recent findings highlight that interactions between small venous smooth muscle cells and endothelial cells in breast tumors are critical for the infiltration of immune cells (e.g., T cells, B cells), suggesting a potential target for enhancing immunotherapy efficacy (80).

Current research directions primarily focus on combining immunotherapy with chemotherapy, targeted therapy, and radiotherapy. For instance, chemotherapy may create a favorable context for immunotherapy by inducing immunogenic cell death. Novel strategies, including those using genetically engineered tumor cells, are also under investigation. Adjunctive approaches such as certain biological therapies (e.g., interferon, interleukin-2) and adoptive cell therapies aim to modulate the body’s immune response against tumors. However, specific application data for these therapies in breast leiomyosarcoma remain limited.

However, our research found that patients with tumors larger than 7cm have a worse prognosis. Does this mean that patients with tumors larger than 7 cm may need to receive additional treatment besides surgery, in addition to other high-risk factors. Although, it is unclear whether treatment is beneficial or has any impact on morbidity and mortality. The combination of anthracyclines with the addition of ifosfamide has been described as first-line chemotherapy (43). There is also emerging evidence to support the use of neoadjuvant chemotherapy for the treatment of metastatic disease, but the results remain uncertain (66).

Hematogenous spread is the most common mode of metastasis in leiomyosarcoma (43). Distant hematogenous metastases to bone, liver, lungs, central nervous system and spine reported in about 25% of cases, and usually detected after a latent period of 15–20 years (5, 74). In patients with metastatic disease, palliative chemotherapy or palliative surgery may be offered to slow disease progression and control local complications (43, 81). Patients with this malignancy have a relatively poor prognosis and a high risk of recurrence compared to other types of breast cancer, with 5-year disease-free survival rates ranging from 33%-52% (82), making frequent follow-up and monitoring for post-excision recurrence necessary.

Our study provides the first systematic evidence that surgical approach, gender, age, and tumor location are not significantly associated with the prognosis of primary breast leiomyosarcoma. In contrast, tumor size was identified as an independent predictor of survival. Consequently, initial tumor size may be considered a key factor in guiding treatment decisions and identifying patients at high risk of recurrence.

But, there a key limitation of this review stems from the inherent methodological constraints of the available primary literature, which predominantly comprises single case reports and small, retrospective case series. Our systematic quality assessment using the JBI tools confirmed these limitations, highlighting frequent deficiencies in standardized follow-up and comprehensive outcome reporting. Consequently, the generalizability and robustness of our pooled findings should be interpreted with caution.

 Data availability statement

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.

 Author contributions

RG: Data curation, Formal Analysis, Investigation, Writing – original draft. WZ: Data curation, Formal Analysis, Investigation, Writing – original draft, Writing – review & editing. XJ: Investigation, Writing – original draft. XL: Data curation, Investigation, Writing – original draft. LH: Supervision, Writing – review & editing.

 Funding

The author(s) declare financial support was received for the research and/or publication of this article. This work was supported in part by the Chengdu University of Traditional Chinese Medicine College Cooperation Innovation Fund (LH202402003); Research Project of Chengdu Municipal Health Commission (WXLH202403256); the Science and technology project of the Health planning committee of Sichuan and Chengdu (2024276 & 2020035 & 2021115); Xinglin Scholars Program of Chengdu University of Traditional Chinese Medicine (YYZX2021039), Chengdu Fifth People’s Hospital Scientific Research Project (KYJJ2021-05) and Chengdu Fifth People’s Hospital Teaching Reform Research Project (JGZX202214).

 Acknowledgments

We appreciate the support of the participating patients and the assistance of the participating doctors.

 Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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The author(s) declare that no Generative AI was used in the creation of this manuscript.

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 Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2025.1662132/full#supplementary-material

References Osório C Rodrigues EF Santos M Santos T Nora M . Fungating breast wound: A rare manifestation of primary breast leiomyosarcoma. Cureus. (2023) 15:e33398. doi: 10.7759/cureus.33398, PMID: 36618497 Kaixin C Fengming L . A case of smooth muscle sarcoma of the male breast. Pract J Cancer. (1995), 11. Ilyas MIM Nazir S Xiao PQ . Breast leiomyosarcoma: A systematic review and recommendations for management. Int Surg. (2019) 104:196–202. doi: 10.9738/INTSURG-D-15-00183.1 Testori A Meroni S Voulaz E Alloisio M De Sanctis R Bossi P . Primary breast leiomyosarcoma and synchronous homolateral lung cancer: a case report. J Thorac Dis. (2017) 9:E1054–9. doi: 10.21037/jtd.2017.10.98, PMID: 29312765 Karabulut Z Akkaya H Moray G . Primary leiomyosarcoma of the breast: A case report. J Breast Cancer. (2012) 15:124–7. doi: 10.4048/jbc.2012.15.1.124, PMID: 22493639 Duncan MA Lautner MA . Sarcomas of the breast. Surg Clinics North America. (2018) 98:869–76. doi: 10.1016/j.suc.2018.03.013, PMID: 30005780 Crocker DJ Murad TM . Ultrastructure of fibrosarcoma in a male breast. Cancer. (1969) 23:891–9. doi: 10.1002/1097-0142(196904)23:4<891::AID-CNCR2820230426>3.0.CO;2-Z, PMID: 5775980 Masadah R Anwar F Nelwan BJ Faruk M . Primary leiomyosarcoma of the breast: A case report and literature review. Int J Surg Case Rep. (2023) 106:108290. doi: 10.1016/j.ijscr.2023.108290, PMID: 37148719 Pardo-Mindán J Garcia-Julian G Eizaguirre Altuna M . Leiomyosarcoma of the breast. Report of a case. Am J Clin Pathol. (1974) 62:477–80. doi: 10.1093/ajcp/62.4.477, PMID: 4414079 Barnes L Pietruszka M . Sarcomas of the breast: a clinicopathologic analysis of ten cases. Cancer. (1977) 40:1577–85. doi: 10.1002/1097-0142(197710)40:4<1577::AID-CNCR2820400430>3.0.CO;2-D, PMID: 907972 Hernandez FJ . Leiomyosarcoma of male breast originating in the nipple. Am J Surg Pathol. (1978) 2:299–304. doi: 10.1097/00000478-197809000-00006, PMID: 686233 Chen KT Kuo TT Hoffmann KD . Leiomyosarcoma of the breast: a case of long survival and late hepatic metastasis. Cancer. (1981) 47:1883–6. doi: 10.1002/1097-0142(19810401)47:7<1883::AID-CNCR2820470728>3.0.CO;2-T, PMID: 7194732 Callery CD Rosen PP Kinne DW . Sarcoma of the breast. A study of 32 patients with reappraisal of classification and therapy. Ann Surg. (1985) 201:527–32. doi: 10.1097/00000658-198504000-00020, PMID: 3977455 Gobardhan AB . Primary leiomyosarcoma of the breast. Netherlands J Surg. (1984) 36:116–8., PMID: 6493566 Yatsuka K Mihara S Isobe M Edakuni S Takeoka A Kakegawa T . Leiomyosarcoma of the breast–a case report and an electron microscopic study. Japanese J Surg. (1984) 14:494–8. doi: 10.1007/BF02469792, PMID: 6543377 Nielsen BB . Leiomyosarcoma of the breast with late dissemination. Virchows Archiv A Pathol Anat Histopathol. (1984) 403:241–5. doi: 10.1007/BF00694900, PMID: 6428038 Yamashina M . Primary leiomyosarcoma in the breast. Japanese J Clin Oncol. (1987) 17:71–7., PMID: 3560465 Arista-Nasr J Gonzalez-Gomez I Angeles-Angeles A Illanes-Baz E Brandt-Brandt H Larriva-Sahd J . Primary recurrent leiomyosarcoma of the breast. Case report with ultrastructural and immunohistochemical study and review of the literature. Am J Clin Pathol. (1989) 92:500–5. doi: 10.1093/ajcp/92.4.500, PMID: 2679042 Lonsdale RN Widdison A . Leiomyosarcoma of the nipple. Histopathology. (1992) 20:537–9. doi: 10.1111/j.1365-2559.1992.tb01042.x, PMID: 1607155 Parham DM Robertson AJ Hussein KA Davidson AI . Leiomyosarcoma of the breast; cytological and histological features, with a review of the literature. Cytopathology. (1992) 3:245–52. doi: 10.1111/j.1365-2303.1992.tb00514.x, PMID: 1421007 Waterworth PD Gompertz RH Hennessy C Henry JA Lennard TW . Primary leiomyosarcoma of the breast. Br J Surg. (1992) 79:169–70. doi: 10.1002/bjs.1800790225, PMID: 1555069 Wei CH Wan CY Chen A Tseng HH . Epithelioid leiomyosarcoma of the breast: report of a case. J Formos Med Assoc. (1993) 92:379–81., PMID: 8104588 Boscaino A Ferrara G Orabona P Donofrio V Staibano S De Rosa G . Smooth muscle tumors of the breast: clinicopathologic features of two cases. Tumori. (1994) 80:241–5. doi: 10.1177/030089169408000316, PMID: 8053085 Falconieri G Della Libera D Zanconati F Bittesini L . Leiomyosarcoma of the female breast: report of two new cases and a review of the literature. Am J Clin Pathol. (1997) 108:19–25. doi: 10.1093/ajcp/108.1.19, PMID: 9208974 Uğraş S Dilek ON Karaayvaz M Dilek H Peker O Barut I . Primary leiomyosarcoma of the breast. Surg Today. (1997) 27:1082–5. doi: 10.1007/BF02385794, PMID: 9413066 González-Palacios F . Leiomyosarcoma of the female breast. Am J Clin Pathol. (1998) 109:650–1. doi: 10.1093/ajcp/109.5.650, PMID: 9576587 Gupta RK Kenwright D Naran S Lallu S Fauck R . Fine needle aspiration cytodiagnosis of leiomyosarcoma of the breast. A case report. Acta Cytol. (2000) 44:1101–5. doi: 10.1159/000328606, PMID: 11127743 Székely E Madaras L Kulka J Járay B Nagy L . Leiomyosarcoma of the female breast. Pathol Oncol Res: POR. (2001) 7:151–3. doi: 10.1007/BF03032583, PMID: 11458280 Kusama R Fujimori M Hama Y Shingu K Ito K Mochizuki Y . Stromal sarcoma of the breast with leiomyosarcomatous pattern. Pathol Int. (2002) 52:534–9. doi: 10.1046/j.1440-1827.2002.01386.x, PMID: 12366813 Shinto O Yashiro M Yamada N Matsuoka T Ohira M Ishikawa T . Primary leiomyosarcoma of the breast: report of a case. Surg Today. (2002) 32:716–9. doi: 10.1007/s005950200133, PMID: 12181723 Liang WC Sickle-Santanello BJ Nims TA Accetta PA . Primary leiomyosarcoma of the breast: a case report with review of the literature. Breast J. (2003) 9:494–6. doi: 10.1046/j.1524-4741.2003.09613.x, PMID: 14616945 Markaki S Sotiropoulou M Hanioti C Lazaris D . Leiomyosarcoma of the breast. A clinicopathologic and immunohistochemical study. Eur J Obstet Gynecol Reprod Biol. (2003) 106:233–6. doi: 10.1016/S0301-2115(02)00226-9, PMID: 12551801 Jun Wei X Hiotis K Garcia R Hummel Levine P . Leiomyosarcoma of the breast: a difficult diagnosis on fine-needle aspiration biopsy. Diagn Cytopathol. (2003) 29:172–8. doi: 10.1002/dc.10359, PMID: 12951688 Adem C Reynolds C Ingle JN Nascimento AG . Primary breast sarcoma: clinicopathologic series from the Mayo Clinic and review of the literature. Br J Cancer. (2004) 91:237–41. doi: 10.1038/sj.bjc.6601920, PMID: 15187996 Lee J Li S Torbenson M Liu QZ Lind S Mulvihill JJ . Leiomyosarcoma of the breast: a pathologic and comparative genomic hybridization study of two cases. Cancer Genet Cytogenet. (2004) 149:53–7. doi: 10.1016/S0165-4608(03)00286-3, PMID: 15104283 Munitiz V Rios A Canovas J Ferri B Sola J Canovas P . Primitive leiomyosarcoma of the breast: case report and review of the literature. Breast (Edinburgh Scotland). (2004) 13:72–6. doi: 10.1016/j.breast.2003.09.004, PMID: 14759721 Stafyla VK Gauvin JM Farley DR . A 53-year-old woman with a leiomyosarcoma of the breast. Curr Surg. (2004) 61:572–5. doi: 10.1016/j.cursur.2004.05.008, PMID: 15590026 Jayaram G Jayalakshmi P Yip CH . Leiomyosarcoma of the breast: report of a case with fine needle aspiration cytologic, histologic and immunohistochemical features. Acta Cytol. (2005) 49:656–60. doi: 10.1159/000326256, PMID: 16450908 Gupta RK . Needle aspiration cytology and immunohistologic findings in a case of leiomyosarcoma of the breast. Diagn Cytopathol. (2007) 35:254–6. doi: 10.1002/dc.20618, PMID: 17351941 De la Pena J Wapnir I . Leiomyosarcoma of the breast in a patient with a 10-year-history of cyclophosphamide exposure: a case report. cases J. (2008) 1:301. doi: 10.1186/1757-1626-1-301, PMID: 18992149 Wong LC Huang PC Luh SP Huang CS . Primary leiomyosarcoma of the nipple-areola complex: report of a case and review of literature. J Zhejiang Univ Sci B. (2008) 9:109–13. doi: 10.1631/jzus.B0720246, PMID: 18257132 Cobanoglu B Sezer M Karabulut P Ozer S Murat A . Primary leiomyosarcoma of the breast. Breast J. (2009) 15:423–5. doi: 10.1111/j.1524-4741.2009.00752.x, PMID: 19601949 Amberger M Park T Petersen B Baltazar GA . Primary breast leiomyosarcoma with metastases to the lung in a young adult: Case report and literature review. Int J Surg Case Rep. (2018) 47:34–7. doi: 10.1016/j.ijscr.2018.04.010, PMID: 29705677 Singh G Sharma D Goyal S . Primary leiomyosarcoma of breast presenting with metastasis: an atypical presentation with dismal prognosis. Indian J Med Paediatric Oncol. (2017) 38:535–7. doi: 10.4103/ijmpo.ijmpo_139_16, PMID: 29333025 Cunli Y Lindu H Xiulin X . Report of a case of breast leiomyosarcoma. Med Forum. (2015) 19:2838 + 2881. Jiafan H Ningxia W Rongzheng L Zhao P Weili H Xin H . A case of primary breast smooth muscle sarcoma in a man. Chin J Breast Disease(Electronic Edition). (2013) 7:66–8. Juan Y Gang L . Report of a case of breast epithelioid smooth muscle sarcoma diagnosed by ultrasound. Jilin Med J. (2014) 35:7551. Mingzhen X . Clinicopathological observations on primary smooth muscle sarcoma of the breast. Natl Med Front China. (2013) 8:93–4. Na W Hongzhang C . A case of primary smooth muscle sarcoma of the breast. J Modern Oncol. (2012) 20:621–2. Luping B Futing J Ming H . Report of a case of smooth muscle sarcoma of the male breast. J Chin Phys. (2003) 5:276. Jian Z . A case of primary breast smooth muscle sarcoma in a male. J Dalian Med Univ. (2010) 32:496. Xiaojun J Shenglu W Yaping L . A case of breast leiomyosarcoma. Ningxia Med J. (2006), 16. Xiaojun L Guangxian Z Chuansheng X Junying L . A case of giant breast smooth muscle sarcoma in a male. J Air Force Med Univ. (2002), 1721. Peng Y Hongjiang W Zhongyu W . 2 cases of breast smooth muscle sarcoma. China J Gen Surg. (2006), 84. Xu T Chunlin W Qixiang G . Report of a case of smooth muscle sarcoma of the breast. Pract Oncol J. (1999) 279. Tianhui W . Two cases of primary giant smooth muscle sarcoma of the breast. J Cancer Control Treat. (2001) 143. Yaokun C Qiming S . Primary smooth muscle sarcoma of the breast (with report of 2 cases). J Pract Oncol. (2001) 16. Renya Z . A case of primary angio-smooth muscle sarcoma in the breast. Cancer Res Prev Treat. (1994) 127. Peijin W . A case of intra-mammary smooth muscle sarcoma. Chin J Oncol. (1995) 166. Jin W Yu F Junying A Nannan L Qiang G Li F . A case of primary smooth muscle sarcoma of the breast. Chin J Pathol. (2013) 42:766–7. Yongjun W Cuiling L . A case of primary smooth muscle sarcoma of the breast. Chin J Oncol. (1997) 42. Huaping G Xuyou L . A case of primary smooth muscle sarcoma of the breast. Cancer Res Prev Treat. (2005), 222–57. Samenova D Midlenko A Khamzina Y Kaldybayev M Khamzina S . Primary leiomyosarcoma of the breast: A successful surgical treatment in a 45-year-old woman. Am J Case Rep. (2023) 24:e939437. doi: 10.12659/AJCR.939437, PMID: 37599433 Sethi E Misra S Ahuja A . Primary leiomyosarcoma with osteosarcomatous differentiation of the breast. Autopsy Case Rep. (2024) 14:e2024476. doi: 10.4322/acr.2024.476, PMID: 38487032 Félix C Bispo M Chagas C . Pancreatic metastasis from primary leiomyosarcoma of the breast. GE Portuguese J Gastroenterol. (2019) 26:223–5. doi: 10.1159/000489866, PMID: 31192295 Miyazaki C Shiozawa M Koike R Ogihara K Sasaki Y Shiba S . Neoadjuvant chemotherapy for primary sarcoma of the breast: a case report. J Med Case Rep. (2019) 13:289. doi: 10.1186/s13256-019-2197-2, PMID: 31488201 Galama R Matoso J Capela G Bôto C Duarte C Mendes AR . A rare etiology of a large tumoral mass of the breast - Case report primary leiomyosarcoma and osteosarcoma of the breast. Int J Surg Case Rep. (2021) 78:201–3. doi: 10.1016/j.ijscr.2020.12.050, PMID: 33360630 Lesar M Juzbasić S Stanec M Vrdoljak DV Milas I Bublić J . Leiomyosarcoma of the breast. Acta Med Croatica: Casopis Hravatske Akademije Medicinskih Znanosti. (2003) 57:315–7., PMID: 14639868 Surov A Holzhausen H-J Ruschke K Spielmann RP . Primary breast sarcoma: prevalence, clinical signs, and radiological features. Acta Radiol. (2011) 52:597–601. doi: 10.1258/ar.2011.100468, PMID: 21565891 McGowan TS Cummings BJ O'Sullivan B Catton CN Miller N Panzarella T . An analysis of 78 breast sarcoma patients without distant metastases at presentation. Int J Radiat Oncol Biol Phys. (2000) 46:383–90. doi: 10.1016/S0360-3016(99)00444-7, PMID: 10661345 Lee JS Yoon K Onyshchenko M Verhoef C . Sarcoma of the breast: clinical characteristics and outcomes of 991 patients from the national cancer database. Sarcoma. (2021) 2021:1–7. doi: 10.1155/2021/8828158, PMID: 33542674 Cheikh TE Hamza K Hicham B Fatiha EM Hajar EO Mustapha B . Leiomyosarcoma of the male breast: Case report. Ann Med Surg. (2021) 67:102495. doi: 10.1016/j.amsu.2021.102495, PMID: 34168877 Yener O Aksoy F . Leiomyosarcoma of the female breast: report of a case. Indian J Surg. (2011) 75:90–2. doi: 10.1007/s12262-011-0353-z, PMID: 24426525 Singh G Sharma D Goyal S . Primary leiomyosarcoma of breast presenting with metastasis: an atypical presentation with dismal prognosis. Indian J Med Paediatric Oncol. (2021) 38:535–7. doi: 10.4103/ijmpo.ijmpo_139_16, PMID: 29333025 Rupert M.P.A.C.K.L. Fehl CAAJ . A patient-centered approach for the treatment of fungating breast wounds. J Adv Practitioner Oncol. (2020) 11:503–10. doi: 10.6004/jadpro.2020.11.5.6, PMID: 32974074 Anastasiou E Lorentz KO Stein GJ Mitchell PD . Prehistoric schistosomiasis parasite found in the Middle East. Lancet Infect Dis. (2014) 14:553–4. doi: 10.1016/S1473-3099(14)70794-7, PMID: 24953264 Lamyman MJ Giele HP Critchley P Whitwell D Gibbons M Athanasou NA . Local recurrence and assessment of sentinel lymph node biopsy in deep soft tissue leiomyosarcoma of the extremities. Clin Sarcoma Res. (2011) 1:7. doi: 10.1186/2045-3329-1-7, PMID: 22612847 Wagner MJ Zhang Y Cranmer LD Loggers ET Black G McDonnell S . A phase 1/2 trial combining avelumab and trabectedin for advanced liposarcoma and leiomyosarcoma. Clin Cancer Res. (2022) 28:2306–12. doi: 10.1158/1078-0432.CCR-22-0240, PMID: 35349638 Italiano A Bellera C D'Angelo S . PD1/PD-L1 targeting in advanced soft-tissue sarcomas: a pooled analysis of phase II trials. J Hematol Oncol. (2020) 13:55. doi: 10.1186/s13045-020-00891-5, PMID: 32430039 Xi C Wencheng Z Dong Q Yong G Cihui Y Yuwen W . Tumor regression after combination of radiation and PD-1 antibody nivolumab treatment in a patient with metastatic mediastinal leiomyosarcoma: a case report. Cancer Biol Ther. (2019) 20:408–12. doi: 10.1080/15384047.2018.1537577, PMID: 30388926 Amaadour L Benbrahim Z Moumna K Boudahna L Amarti A Arifi S . Primary breast leiomyosarcoma. Case Rep Oncol Med. (2013) 2013:1–4. doi: 10.1155/2013/732730, PMID: 24455361 Horton L Wohlfeil M Al-Kourainy N Choi L . Rare case of primary leiomyosarcoma of the breast treated with wide local excision and planned cosmetic breast reduction surgery. BMJ Case Rep. (2020) 13:e236013. doi: 10.1136/bcr-2020-236013, PMID: 33257357