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1. Introduction
Breast cancer is the most prevalent malignant tumor among women and the leading cause of cancer-related deaths worldwide(1). Additionally, breast cancer has a high prevalence of metastasis to various organs, including the bones, brain, and lungs(2,3). Major factors influencing breast cancer include reproductive factors (such as early menarche, late menopause, age at first pregnancy, and breastfeeding) and individual risk factors (such as breast density, family history of the disease, and genetic mutations)(4).
Breast cancer is a heterogeneous disease, with genetics playing an important role in only 5-10% of cases(5). In the remaining 90-95% of cases, lifestyle factors are the main contributors. For this reason, primary prevention focuses on eliminating risk behaviors, such as alcohol consumption, engaging in regular physical activity, controlling certain diseases like diabetes, and preventing obesity. Subsequently, secondary prevention includes medical investigations, early disease detection, and treatment in the early stages of the disease(6).
Metastases significantly contribute to increased breast cancer mortality. Metastasis involves the dissemination of cancer cells, and the pattern of metastatic spread is not random; cancer cells show specific preferences for colonizing distant organs. Once metastases occur, breast cancer remains treatable but not curable. Although the survival rates have improved over recent decades, patients with metastases at diagnosis still have a low five-year survival rate(7-10).
Bone is the most common site for breast cancer metastasis, and bone metastases are a major mortality factor(11). In addition to the challenges of treatment, metastases are associated with pain, reduced mobility, hypercalcemia, pathological fractures, spinal cord compression, and aplastic anemia(12). Bone metastases and metastases in general present significant challenges in oncology.
2. Materials and method
This study is a retrospective analysis of 37 patients diagnosed with breast cancer, who subsequently developed bone metastases between 2014 and 2024, at the Oncology Surgery Clinic I of the “Prof. Dr. Alexandru Trestioreanu” Institute of Oncology, Bucharest, Romania. Medical records were examined for patients’ age at diagnosis, cancer stage at diagnosis, time elapsed until the appearance of bone metastases, location of the primary tumor, site of bone metastases, survival, histopathology of the primary tumor, specific hormonal receptors of the primary tumor, presence of metastases in various organs, patients’ mortality, and characteristics of the bone metastases. Exclusion criteria: patients with two or more primary tumors in addition to the primary breast tumor, or patients with insufficient medical records to complete the database. Inclusion criteria: patients diagnosed with breast cancer and bone metastases, as well as patients who were diagnosed with breast cancer before 2014-2024, but developed bone metastases during the 2014-2024 period.
3. Results
Table 1 highlights the clinical data of the patients registered in our study.
Figure 1 presents statistical data on the preferred sites of bone metastases. The analysis indicates that the spine is the most frequently affected bone, with 12 reported cases, followed by the ribs, with seven cases. The pelvis and humerus have an equal incidence of metastases, with five cases each, while the skull and femur show a similar pattern, with four cases each. The breastbone is the least affected site, with only three reported cases.
Figure 2 illustrates the correlation between the number of metastases and the age of patients at diagnosis. Age is a significant factor in breast cancer, with older patients facing a heightened risk of developing the disease. While younger individuals are not at an increased overall risk, when they do develop cancer, it tends to be more aggressive. Additionally, younger patients are often diagnosed at later stages, largely due to the absence of targeted prevention strategies for this age group.
Figure 3 displays the frequency of associations between bone metastases and metastases in the liver, lungs, and brain. Consistent with findings from other studies, after spreading to the bones, breast cancer cells most commonly metastasize to the lungs, liver, and brain. These metastatic associations are linked to reduced survival rates, with brain metastases resulting in the most pronounced decline (7%), followed by liver metastases (48%), and lung metastases (45%).
Figure 4 illustrates the distribution of bone metastasis types: 28% are osteolytic, 17% are osteoblastic, 33% are mixed, and 22% are unspecified. Osteolytic metastases are the most prevalent type across various cancers. Osteoblastic metastases, which occur in only 20% of breast cancer cases, are less common but more specific than osteolytic metastases. They are frequently associated with increased bone pain and with a higher incidence of pathological fractures.
4. Discussion
The development of bone metastases is influenced by various factors related to the microenvironment and the availability of growth factors. Metastasis involves the dissemination of cancer cells, and the pattern of metastatic spread is not random; cancer cells have specific preferences for colonizing distant organs(13,14).
In 1889, Stephen Paget published his “seed and soil” theory, which explains the interaction between primary tumor cells and host organs. Bones are a common site for breast cancer metastasis, as the bone matrix provides a favorable environment for cancer cell development. According to Paget’s theory, bones represent the ideal “soil” for breast cancer cells to “seed”(15,16). Bone metastases – and metastases, in general – present significant challenges in oncology. About 90% of deaths from breast cancer are due to metastases, and the five-year survival rate for metastatic cancer is just over 20%. Metastatic disease is incurable, and the only option is palliation, which aims to improve the patient’s quality of life and extend the survival(17).
In the case of bone metastases, the health of the musculoskeletal system becomes a crucial issue. Although bone metastases are not inherently life-threatening, they significantly reduce the patient’s autonomy and quality of life. Breast cancer cells often spread to the bone marrow long before metastases become symptomatic or detectable through diagnostic tests. Dormant cells may be present in this area, which can either remain localized, creating lesions detectable later, or spread throughout the skeleton(18,19).
Bone metastases are classified into two categories: osteolytic and osteoblastic. The distinction is based on the predominant activity of certain cells. Under normal conditions, there is a balance between bone formation and bone resorption. However, this balance is disrupted by breast cancer cells that are brought to this site through the bloodstream. The growth of malignant cells disturbs the bone microenvironment, stimulating osteolysis through osteoclasts, leading to osteolytic bone metastases, or inducing osteosclerosis through osteoblasts, resulting in osteoblastic metastases. The specialized literature has shown through numerous studies that bone metastases often have both osteolytic and osteoblastic components(20-23).
Bone metastases, although not life-threatening on their own, present a significant health issue that requires multidisciplinary care, due to the numerous complications they cause, such as pain, bleeding, infections, tumor progression, and damage to blood vessels and nerves. Bone metastases in the upper cervical region, through the complications they produce, can lead to paralysis(24-29).
5. Conclusions
Breast cancer is a significant challenge for healthcare systems worldwide, and the development of bone metastases further complicates both medical treatment and the patient’s quality of life. Breast cancer behaves differently, depending on the patient’s age, hormone receptor status, and the presence of subsequent metastases. It is a disease with an incidence that surpasses all other tumors in both sexes, and it has the highest mortality rate among women.
Autori pentru corespondenţă: Laurenţiu SimionE-mail: lasimion@yahoo.com
CONFLICT OF INTEREST: none declared.
FINANCIAL SUPPORT: none declared.
This work is permanently accessible online free of charge and published under the CC-BY.
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