ORIGINAL ARTICLE

Risks, survival and prognosis in female patients with breast cancer who developed bone metastases – a retrospective study

 Riscuri, supravieţuire şi prognostic în cazul pacientelor cu cancer mamar care au dezvoltat metastaze osoase – studiu retrospectiv

First published: 18 octombrie 2024

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/OnHe.68.3.2024.10157

Abstract

Introduction. Breast cancer has the highest incidence among cancers, with 46.2 cases per 100,000, and it also has the highest mortality rate among all types of malignant tu­mors, at 16.6 per 100,000. Objectives. Breast cancer is the most common cancer among female patients and has the highest mortality rate among malignant di­sea­ses. Bone meta­stasis is the most common site for the colonization of ma­lig­nant breast cells. This study in­ves­ti­gates the correlation be­tween survival, the number of me­ta­sta­ses, and their frequency. Materials and method. The database consists of 37 female patients with breast can­cer as the primary tumor, who subsequently developed bone metastases between 2014 and 2024. The analyzed data include information about the primary tumor, bone me­ta­sta­ses, metastases in other organs, adenopathies, and deaths. 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. Results. In addition to analyzing da­ta related to bone metastases, biological factors were also exa­mined. Conclusions. The occurrence of bone me­ta­sta­ses re­pre­sents an unknown negative prognostic factor. How­ever, modern treatment methods are capable of improving disease pro­gres­sion and patients’ quality of life.
 

Keywords
breast cancer, bone metastases, breast cancer prognosis

Rezumat

Introducere. Cancerul mamar prezintă cea mai ridicată in­ci­den­ţă dintre toate tipurile de cancer, cu 46,2 cazuri la 100000 de lo­cui­tori şi, de asemenea, are cea mai mare rată de mortalitate din­tre tumorile maligne, de 16,6 la 100000. Obiective. Cancerul ma­mar este cel mai frecvent neoplasm în rândul pacientelor şi are cea mai mare rată de mortalitate dintre bo­li­le maligne. Me­ta­sta­zele osoase reprezintă cel mai comun loc de colonizare pen­tru celulele maligne mamare. Acest stu­diu investighează co­re­la­ţia dintre supravieţuire, numărul de me­ta­s­taze şi frecvenţa aces­to­ra. Materiale şi metodă. Baza de date cu­prinde 37 de pa­­cien­te cu cancer mamar ca tumoră primară, care au dez­vol­tat ulterior metastaze osoase, între anii 2014 şi 2024. Datele ana­li­zate includ informaţii despre tumora primară, metastazele osoa­se, metastazele în alte organe, adenopatii şi decese. Cri­te­rii de excludere: paciente cu două sau mai multe tumori pri­mare în afară de tumora mamară primară sau pa­cien­te cu do­sa­re medicale insuficiente pentru completarea bazei de date. Cri­te­rii de includere: paciente diagnosticate cu cancer ma­mar şi metastaze osoase, precum şi paciente care au fost diag­nos­ti­ca­te cu cancer mamar înainte de 2014-2024, dar care au dez­vol­tat metastaze osoase în această perioadă. Rezultate. Pe lângă analiza datelor referitoare la metastazele osoase, au fost examinaţi şi factorii biologici asociaţi. Concluzii. Apariţia meta­sta­ze­lor osoase reprezintă un factor de prognostic negativ necunoscut. Cu toate acestea, metodele moderne de tratament sunt capabile să îmbunătăţească evoluţia bolii şi calitatea vieţii pacienţilor.
 

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.
 

Table 1. Clinical characteristics of the patients registered in the study
Table 1. Clinical characteristics of the patients registered in the 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 1. The most common sites of bone metastases
Figure 1. The most common sites of bone metastases

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 2. Statistics regarding the correlation between the number of bone metastases and the patients’ age at diagnosis
Figure 2. Statistics regarding the correlation between the number of bone metastases and the patients’ age at diagnosis

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 3. Frequency of associations between bone metastases and metastases in the liver, lungs, and brain
Figure 3. Frequency of associations between bone metastases and metastases in the liver, lungs, and brain

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.
 

Figure 4. Distribution of the type of bone metastases
Figure 4. Distribution of the type of bone metastases

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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Bibliografie

  1. Cancer Today – Global Cancer Observatory. https://gco.iarc.fr/today/en

  2. Ivanova M, Porta FM, Giugliano F, et al. Breast Cancer with Brain Metastasis: Molecular Insights and Clinical Management. Genes. 2023;14(6):1160. 

  3. Wu SG, Li H, Tang LY, Sun JY, Zhang WW, Li FY, Chen YX, He ZY. The effect of distant metastases sites on survival in de novo stage-IV breast cancer: A SEER database analysis. Tumour Biol. 2017;39(6):1010428317705082. 

  4. Sun YS, Zhao Z, Yang ZN, Xu F, Lu HJ, Zhu ZY, Shi W, Jiang J, Yao PP, Zhu HP. Risk Factors and Preventions of Breast Cancer. Int J Biol Sci. 2017;13(11):1387-1397.

  5. Akram M, Iqbal M, Daniyal M, Khan AU. Awareness and current knowledge of breast cancer. Biol Res. 2017;50(1):33. 

  6. Kolak A, Kamińska M, Sygit K, Budny A, Surdyka D, Kukiełka-Budny B, Burdan F. Primary and secondary prevention of breast cancer. Ann Agric Environ Med. 2017;24(4):549-553.

  7. Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol. 2022;95(1130):20211033. 

  8. Largillier R, Ferrero JM, Doyen J, Barriere J, Namer M, Mari V, Courdi A, Hannoun-Levi JM, Ettore F, Birtwisle-Peyrottes I, Balu-Maestro C, Marcy PY, Raoust I, Lallement M, Chamorey E. Prognostic factors in 1,038 women with metastatic breast cancer. Ann Oncol. 2008;19(12):2012-9. 

  9. Huang Z, Hu C, Liu K, Yuan L, Li Y, Zhao C, Hu C. Risk factors, prognostic factors, and nomograms for bone metastasis in patients with newly diagnosed infil­tra­ting duct carcinoma of the breast: a population-based study. BMC Cancer. 2020;20(1):1145.

  10. Liu Z, Xue J, Liu K, Fan Z, Liu D, Wang D. Risk, Prognostic Factors and Nomograms for Bone Metastasis in Young Females with Breast Cancer: A Large Cohort Retrospective Study. Altern Ther Health Med. 2023;29(1):182-190. 

  11. Vrabie EM, Alecu M, Cirimbei C, et al. The Management of Axillary Lymph Nodes in Breast Cancer – A Retrospective Single-Centre Study. Chirurgia (Bucur). 2021;116(2):186-192.

  12. Jayarangaiah A, Kemp AK, Theetha Kariyanna P. Bone Metastasis. 2023 Jul 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–.

  13. Wang M, Xia F, Wei Y, et al. Molecular mechanisms and clinical management of cancer bone metastasis. Bone Res. 2020;8(1):30. 

  14. Simion L, Petrescu I, Chitoran E, et al. Breast Reconstruction following Mastectomy for Breast Cancer or Prophylactic Mastectomy: Therapeutic Options and Results. Life (Basel). 2024;14(1):138.

  15. Akhtar M, Haider A, Rashid S, Al-Nabet ADMH. Paget’s “Seed and Soil” Theory of Cancer Metastasis: An Idea Whose Time has Come. Adv Anat Pathol. 2019;26(1):69-74. 

  16. Weber CE, Kuo PC. The tumor microenvironment. Surg Oncol. 2012;21(3):172-7.

  17. Fields RC, Jeffe DB, Trinkaus K, et al. Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage IV breast cancer after controlling for site of metastasis. Ann Surg Oncol. 2007;14(12):3345-3351.

  18. Pauk M, Saito H, Hesse E, Taipaleenmäki H. Muscle and Bone Defects in Metastatic Disease. Curr Osteoporos Rep. 2022;20(5):273-289.

  19. Weber MH, Goltzman D, Kostenuik P, Rabbani S, Singh G, Duivenvoorden WC, Orr FW. Mechanisms of tumor metastasis to bone. Crit Rev Eukaryot Gene Expr. 2000;10(3-4):281-302.

  20. Yang W, Pan Q, Huang F, Hu H, Shao Z. Research progress of bone metastases: From disease recognition to clinical practice. Front Oncol. 2023;12:1105745. 

  21. Yin JJ, Pollock CB, Kelly K. Mechanisms of cancer metastasis to the bone. Cell Res. 2005;15(1):57-62.

  22. Venetis K, Piciotti R, Sajjadi E, Invernizzi M, Morganti S, Criscitiello C, Fusco N. Breast Cancer with Bone Metastasis: Molecular Insights and Clinical Management. Cells. 2021;10(6):1377. 

  23. Riquelme MA, Cardenas ER, Jiang JX. Osteocytes and Bone Metastasis. Front Endocrinol (Lausanne). 2020;11:567844. 

  24. Confavreux CB, Follet H, Mitton D, Pialat JB, Clézardin P. Fracture Risk Evaluation of Bone Metastases: A Burning Issue. Cancers (Basel). 2021;13(22):5711.

  25. Sofi AA, Mohamed I, Koumaya M, Kamaluddin Z. Local therapy in metastatic breast cancer is associated with improved survival. Am J Ther. 2013;20(5):487-492.

  26. Ibragimova MK, Tsyganov MM, Kravtsova EA, Tsydenova IA, Litviakov NV. Organ-Specificity of Breast Cancer Metastasis. Int J Mol Sci. 2023;24(21):15625.

  27. Jimenez-Andrade JM, Mantyh WG, Bloom AP, Ferng AS, Geffre CP, Mantyh PW. Bone cancer pain. Ann N Y Acad Sci. 2010;1198:173-81.

  28. Lan MY, Shiao AS, Li WY. Facial paralysis caused by metastasis of breast carcinoma to the temporal bone. J Chin Med Assoc. 2004;67(11):587-90.

  29. Zhao H, Cai W, Li S, Da Z, Sun H, Ma L, Lin Y, Zhi D. Characterization of neuro­blasto­ma bone invasion/metastasis in established bone metastatic model of SY5Y and KCNR cell lines. Childs Nerv Syst. 2013;29(7):1097-105. 

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