Introduction

Breast cancer is a leading cause of mortality globally, with 2.3 million new cases reported in 185 countries in 2018, according to GLOBOCAN [1]. In the national context, it is the second most common neoplasm, with an estimated annual incidence of 28 cases per 100,000 inhabitants [2].

Within the pathology of breast cancer is primary breast sarcoma, a rare entity, but with high local recurrence and a wide variability in survival, with a range of 15% to 91%, and few reports worldwide [ 3]. This type of sarcoma originates in the mesenchymal tissue of the breast [4], and its biology is complex, with cells interacting in a microenvironment that includes a microbiome with intracellular bacteria that could play specific roles in tumor development [5].

Furthermore, infiltration of macrophages with CD8 markers and CD163 subpopulations has been observed in sarcomas, associated with proangiogenic functions [6], as well as the presence of a group of cancer stem cells that contribute to metastasis and recurrence [7]. The absence of the TRPS1 marker has been identified in breast sarcomas compared to other breast tumors, suggesting a possible common genetic background [8].

Primary breast sarcoma, like other types of sarcomas, can be associated with inherited genetic diseases and environmental factors such as the use of compounds with arsenic and vinyl chloride [9]. The most common histological types include angiosarcoma and pleomorphic sarcoma, which account for approximately half of the cases [10].

A recent study by Gutnik et al found that patients with primary breast sarcoma had worse survival compared to other breast tumors, based on data from American national databases between 2004 and 2016 [11]. The clinical presentation usually occurs in women between 45 and 75 years old, with a predominant location in the left upper quadrant or in the entire breast [12], and mammograms show a hyperdense oval lesion with circumscribed margins and without calcifications [13].

Characteristics and treatments of primary breast sarcomas have been described in various studies. For example, Cuba Gonzales Ortega and colleagues found an incidence of 1.2% in mesenchymal tumors of the breast in a study of registries from 1974 to 2005 [14]. Torres et al describe the case of a patient with breast stromal sarcoma with a good prognosis after surgical resection and adjuvant chemotherapy [15]. Amine Elhadj and colleagues evaluated 30 patients with breast sarcoma in Tunisia and found that adequate excision was associated with a better prognosis [16].

Isolated cases with various histological characteristics and dimensions have been reported, such as a case of granulocytic pattern managed with tumorectomy with disease-free follow-up one year after surgery [17], and another of angiosarcoma in a patient with mastectomy and good survival [18]. A case of primary breast osteosarcoma with lung metastasis despite adequate surgical treatment has also been documented [19].

Additional studies have analyzed prognostic factors in patients with primary breast sarcoma, such as tumor size and histological type. For example, Kim YJ and colleagues found that histological grade was an important survival factor in primary angiosarcoma of the breast [20]. Yin et al, as well as Osman et al, highlighted the influence of tumor size on the overall survival of patients [12, 21].

In summary, ongoing research seeks to determine whether tumor size is a significant prognostic factor in the survival of patients with primary breast sarcoma.

Material and methods

Design of the study

Case-control study nested in cohort.

Study population and sample selection

The population of interest consisted of all patients diagnosed with primary breast sarcoma in the Department of Breast, Skin and Soft Parts of the Regional Institute of Neoplastic Diseases of Northern Peru from January 1, 2010, to December 31, 2020. that met the inclusion criteria. Patients with a histologically confirmed diagnosis of primary breast sarcoma were included, divided into two groups: cases, with a tumor size greater than 5 cm, and controls, with a tumor size less than or equal to 5 cm. Patients who had undergone surgical interventions in other institutions, those with incomplete clinical records and those with a diagnosis of other primary malignant neoplasms were excluded.

The follow-up was carried out for a minimum period of two years and six months and a maximum of three years and six months, with a cut-off point of June 30, 2023.

Procedures and techniques

The corresponding authorization was obtained from the management of the Regional Institute of Neoplastic Diseases to carry out the research at its facilities. Subsequently, data were collected from the medical records of patients diagnosed with primary breast sarcoma who met the established selection criteria.

The data collected were meticulously recorded on a collection sheet designed specifically for this purpose by the author of the study. Subsequently, this information was entered into the SPSS 25 statistical software for further analysis.

Statistical analysis

The IBM SPSS Statistics 25 statistical package was used to process and analyse the data. For the qualitative variables, the results were presented in simple and cross tables with absolute and percentage frequencies. For the quantitative variables, the results were presented with means and standard deviations. To determine the association between the variables, When one of the expected frequencies was less than 5, Fisher’s exact test was used. For the difference between two means in numerical variables, the student t test was used. A p value of less than 5 percent was considered statistically significant. The Kaplan Meier curves were used for the survival curve and the log Rank test was used for the difference between 2 survival curves. Also, the Cox regression was used to evaluate the influence of variables on survival.

Ethical considerations

The study was carried out in compliance with the ethical principles established by the World Health Organization and the Council for International Organizations of Medical Sciences. The corresponding authorization was obtained from the research committee of the Antenor Orrego Private University.

Results

2,173 cases of breast cancer were registered during the period from 2010 to 2020. Of the total, 20 patients were registered with the diagnosis of primary breast sarcoma who met the selection criteria. Yesand divided into 2 groups: 13 patients with a tumor size greater than 5 cm and 7 patients with a tumor size less than 5 cm. The average age in our study was 48 years, with the age group over 40 years being the majority, with 70% of the total cases. Regarding tumor size, an average of 11 cm was found and tumors larger than 5 cm constituted 65%.

In patients with a tumor larger than 5 cm, the frequency of age over 40 years was 61.5%; The right side was the most affected with 53.8% of cases, the most frequently observed histological type was pleomorphic sarcoma with 23.1% of samples; and the predominant type of intervention was surgery with 46.2%, followed by surgery with chemotherapy in 23.1%. (Table 1).

Table 1. Characteristics of patients with primary breast sarcoma

Patients with a tumor smaller than 5 cm, the frequency of age over 40 years was 85.7%; The right side was the most affected with 57.1% of cases, the most frequently observed histological type was poorly differentiated sarcoma with 28.6% of samples; and the predominant type of intervention was s

urgery with 42.9%, followed by surgery with chemotherapy in 28.6%. (Table 1).

The survival time in patients with a tumor size greater than 5 cm was 95.6 weeks, while those with a tumor size less than or equal to 5 cm survived 51.7 weeks. (Figure). Tumor size was not a risk factor for overall survival in this study. (p=0.37) (Table 2).

Survival curves (weeks).

Table 2. Survival depending on tumor size

Regarding the intervening variables for tumor size, age over 40 years, affected side, histological type and type of intervention, no significant statistical differences were found (Table 3).

Table 3. Multivariate analysis of survival depending on different variables in patients with primary breast sarcoma 2020

Discussion

Worldwide, breast cancer is among the most prevalent oncological diseases, projecting an increase of 40% by 2040 [22]. In the region, the “Luis Pinillos Ganoza” Regional Institute of Neoplastic Diseases stands as the reference center for oncology in the north and east of Peru, where breast cancer occupies second place, after cervical cancer [23]. Among the predominant histological subtypes in this region, infiltrating ductal carcinoma and infiltrating lobular carcinoma stand out, although there are other subtypes that make up the remaining 15% [23].

In this study, it is observed that the majority age group is over 40 years old, consistent with findings reported by Yin et al., although their average age was 55 years [12], in contrast to the findings of Kim et al., where the average was 33 years [20]. However, a significant correlation is observed between the reports of Yin et al. and Kim et al. with our study, since the most affected patients belonged to the third and fourth decades of life.

Regarding tumor size, an average of 11 cm was found, similar to the reports by Amine Elhadj et al. in 2017, who mention an average of 10 cm [16], and greater than that reported by Kim et al. in 2022, with an average of 7.7 cm, although their study focused specifically on the angiosarcoma subtype [20]. This finding agrees with the research of Amine Elhadj et al., where the aforementioned tumor size is related to a late diagnosis, due to the prolonged average consultation time, which is linked to the lack of prevention and poor early detection in our reality. national.

In our research, tumors were classified based on a cut-off point of 5 cm, with a greater number found above this value. Although overall survival was not affected in this study, research such as that of Yin et al. mention that tumors larger than 5 cm have a negative impact on survival [12]. Yin et al. suggest that adjuvant radiation improves survival outcomes in patients with tumors larger than 5 cm; however, a similar improvement was not observed in tumors smaller than this size.

Regarding the histological type, we agree with Lee et al. in which spindle cell sarcoma is the most common, followed by angiosarcoma [9]. This observation aligns with our research, where when grouping various sarcoma subtypes together, they constitute more than 55% of cases. This finding coincides with Lim et al., who consider breast angiosarcoma as a risk factor for decreased survival, due to its potential for lymphogenic dissemination [25].

In relation to age, we classified patients into two groups using 40 years as a cut-off point, and we did not find that this affected overall survival. However, the study by Osman et al. showed that age over 60 years is associated with worse survival [21]. Furthermore, they indicate that elderly, non-surgical, unmarried patients with large tumors have a lower overall survival. The discrepancy in the results on the effectiveness of radiotherapy in the treatment of breast sarcoma is also evident, as reflected by the observations of Osman et al. and Amine Elhadj et al.

In our research, despite not finding an association between the types of treatment and survival, it was observed that the majority of patients received surgery (45%). This finding is consistent with the study by Lee et al., where surgical treatment was associated with better survival [9]. However, surgical treatment was not shown to improve survival in the research of Amine Elhadj et al., although they highlight the importance of surgical excision with adequate margins to improve survival [16].

Regarding the regression analysis carried out in our study, no significant model was found with the variables of age, tumor size and type of treatment, which suggests that other variables could influence overall survival. It is suggested to consider a larger number of patients or additional variables to better understand this phenomenon.

Primary breast sarcoma, as mentioned initially, is a pathology with a very low incidence worldwide. At the national level, special histological types of breast cancer such as primary breast sarcoma have not been recorded. This study on primary breast sarcoma is pioneering in our region. However, it faced limitations such as obtaining a small sample due to the low incidence of this pathology, as well as the presence of incomplete medical records, some of which were eliminated due to the renewal of the computer system that stored the records.

Conclusions

It was found that those with tumors smaller than 5 cm had a mean survival of 51.7 weeks, while those with tumors larger than 5 cm had a mean survival of 95.6 weeks. Surprisingly, the multivariate analysis revealed that tumor size greater than 5 cm was not a significant prognostic factor for a decrease in survival in these patients, and in addition, other intervening variables did not show to be prognostic factors for the decrease in survival in this type. of primary breast sarcoma.

Ethical aspects: All authors certify that they meet the current authorship criteria of the International Committee of Medical Journal Editors (ICMJE).

Declaration of conflict of interest:The authors have no conflict of interest to declare.

Funding sources:The authors declare that this work has not received any funding from funding agencies in the public, commercial, or non-profit sectors.

Author contributions:

Conceptualization, Formal research analysis, Methodology, Resources, Software, Validation, Visualization, Approval of the final manuscript.

Writing, Review and editing, Approval of the final manuscript.