Research Article

SCINTIGRAPHIC PATTERN OF SKELETAL METASTASIS BASED ON MOLECULAR SUBTYPES OF BREAST CANCER AT THE DR GEORGE MUKHARI ACADEMIC HOSPITAL GARANKUWA, SOUTH AFRICA

Oiza Tessy Ahmadu1*, Shehu Salihu Umar2, Saad A Ahmed3, Aminu Bello Liman4, Trevor Mdaka5
1 Department of Radiotherapy and Oncology, Federal Medical Centre, Abuja, FCT, Nigeria
2 Department of Radiology, Ahmadu Bello University Zaria, Kaduna State, Nigeria
3 Department of Pathology, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria
4 Ahmadu Bello University Zaria
5 Sefako Makgatho Health Sciences University Teaching Hospital; Dr George Mukhari Academic Hospital, Pretoria, South Africa
* Corresponding author: tessyoiza@yahoo.com
Published: Jan, 2025
DOI: 10.67579/njo.2025.tplwhm7u
Pages: 60-69
Views: 239
Downloads: 137

Abstract

Introduction: The presence of metastasis is the most important factor affecting overall survival of patients with breast cancer. Though tremendous progress has been made in area of treatment, 20-30% of patients will develop metastasis, with the skeleton as one of the major sites of distant spread. There is marked variability among breast cancer patients who develop metastasis including the pattern. The histopathological molecular subtypes of breast cancer have distinct biological features with variability in the metastatic pattern, response to treatment and overall clinical outcome. Bone scintigraphy (bone scan) is the most commonly used imaging modality for the detection of skeletal metastasis and Methylene diphosphonate (MDP) complexed with gamma-emitting radionuclide technetium-99m (99mTc-MDP) is the most commonly used tracer for this imaging.

Objective: To assess the pattern of occurrence and distribution of skeletal metastases detected by 99mTc-MDP bone scintigraphy in the various molecular subtypes of breast cancer at the Dr George Mukhari Academic Hospital Garankuwa, Guateng.

Methods: A retrospective review of all the bone scans of two hundred and two consecutive breast cancer patients irrespective of their clinical details (age, menopausal status, stage, treatment received, presence of other metastatic sites etc.) seen at the Department of Nuclear Medicine of Dr George Mukhari Academic Hospital, Garankuwa South Africa, between 2011 to 2015 was conducted. The patients were classified into four molecular subtypes (Luminal A, Luminal B, Human epidermal growth factor receptor-2 enriched (HER2-enriched) and Triple-negative) based on the expression of estrogen receptor (ER), progesterone receptor (PgR), Human Epidermal Growth Factor Receptor-2 (HER-2) and Ki-67 determined by immunohistochemistry at the time of diagnosis. All the patients had a minimum of two annual bone scans done between 2011 and 2015. The bone scans were reviewed for the presence of skeletal metastases and those with skeletal metastases were further classified into respective histopathologic molecular subtypes. Relevant data related to demographic information, clinical presentation, metastasis pattern, and histopathological details of the patients were retrieved from the case folders and entered into a proforma.

Results: A total of 202 patients met the study eligibility criteria; out of which 106 (52.5%) had skeletal metastasis (positive bone scans). The mean age at presentation of patients was 57.9 years with 77.4% at stages 3 and 4. The majority (72%) of the patients were ER-positive, about (46.2%) were of the Luminal B molecular subtype while Luminal A, triple-negative, and HER2-enriched subtypes accounted for 27.4%, 17% and 9.4% respectively. The highest frequency (77%) of occurrence of bone metastasis was seen in the HER2-enriched subtype. The multiple metastasis pattern of metastasis were the commonest (77.4%) pattern of distribution noted followed by solitary pattern, while super scan pattern was the least common (2.8%). Thoracolumbar vertebrae were the most commonly affected site while bones of the lower extremities had the least affectation. The sternum was the most common site of affectation noted with the solitary pattern of distribution. The multiple metastases pattern of distribution remained the most frequent in all molecular subtypes, the solitary was noted more (71.4%) with the luminal subtypes while super scan was found only in the luminal subtypes.

Conclusion: This study has shown that multiple metastasis pattern of distribution of skeletal lesions remains the most frequent form with the thoracolumbar vertebrae and lower extremities being the most and least affected sites respectively. The solitary and super scan patterns are commonly associated with the luminal subtypes. The findings could guide the development of surveillance protocol to predict bone metastases in breast cancer patients based on molecular subtypes.

Keywords

Breast cancer skeletal metastasis bone scan immunohistochemistry molecular subtypes

References

  1. Savci-Heijink CD, Halfwerk H, Hooijer GKJ, Horlings HM, Wesseling J, van de Vijver MJ. Retrospective analysis of metastatic behaviour of breast cancer subtypes. Breast Cancer Res Treat. 2015;150(3):547-557.
  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. 2018;68(6):394-424.
  3. Early Breast Cancer Trialists' Collaborative Groups. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. The Lancet. 2005;365(9472):1687-1717.
  4. Golubnitschaja O, Debald M, Yeghiazaryan K, Kuhn W, Pešta M, Costigliola V, et al. Breast cancer epidemic in the early twenty-first century: evaluation of risk factors, cumulative questionnaires and recommendations for preventive measures. Tumour Biol. 2016;37(10):12941–57
  5. Huber KE, Carey LA, Wazer DE. Breast Cancer Molecular Subtypes in Patients With Locally Advanced Disease: Impact on Prognosis, Patterns of Recurrence, and Response to Therapy. Seminars in Radiation Oncology. 2009;19(4):204-210.
  6. Hamaoka T, Madewell JE, Podoloff DA, Hortobagyi GN, Ueno NT. Bone imaging in metastatic breast cancer. Journal of Clinical Oncology. 2004;22(14):2942-2953.
  7. Hosen MMA, Begum N, Ahmed P, Hossain M, Khatun S, Chowdhury SI, et al. Pattern of Skeletal Metastasis in Breast Cancer Patients Attending INMAS, Rajshahi. 2018;21(1):21-25.
  8. Kimbung S, Loman N, Hedenfalk I. Clinical and molecular complexity of breast cancer metastases. Seminars in Cancer Biology. 2015;35:85-95.
  9. Stevenson JD, McNair M, Cribb GL, Cool WP. Prognostic factors for patients with skeletal metastases from carcinoma of the breast. Bone Joint J. 2016;98-B(2):266-270.
  10. Kennecke H, Yerushalmi R, Woods R, Cheang MC, Voduc D, Speers CH, et al. Metastatic behavior of breast cancer subtypes. J Clin Oncol. 2010;28(20):3271-3277.
  11. Sihto H, Lundin J, Lundin M, Lehtimäki T, Ristimäki A, Holli K, et al. Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study. Breast Cancer Res. 2011;13(5):R87-R.
  12. Smid M, Wang Y, Zhang Y, Sieuwerts AM, Yu J, Klijn JGM, et al. Subtypes of Breast Cancer Show Preferential Site of Relapse. Cancer Research. 2008;68(9):3108.
  13. Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, et al. Breast Cancer Subtypes Predispose the Site of Distant Metastases. American Journal of Clinical Pathology. 2015;143(4):471-478.
  14. Wildiers H, van Mechelen M, van Herck A, Lobelle JP, Smeets A, Neven P, et al. Differences between breast cancer subtypes in developing metastatic disease. Annals of Oncology. 2019;30(3):157P.
  15. Wu Q, Li J, Zhu S, Wu J, Chen C, Liu Q, et al. Breast cancer subtypes predict the preferential site of distant metastases: a SEER based study. Oncotarget. 2017;8(17):27990-27996.
  16. Gonzalez-Sistal A, Sánchez AB, Carnero MH, Morell AR. Advances in medical imaging applied to bone metastases. Medical Imaging.2011.340-354.
  17. Peepre K, Tiwari AN, Sharma JP. Clinical Significance of 99m Tc-MDP Imaging & Molecular Biology in the Diagnosis of Bone Metastases. IOSR Journal Of Pharmacy. 2014;4(2):50-55.
  18. Houssami N, Costelloe CM. Imaging bone metastases in breast cancer: evidence on comparative test accuracy. Annals of Oncology. 2011;23(4):834-843.
  19. Gates GF. SPECT bone scanning of the spine. Seminars in Nuclear Medicine. 1998;28(1):78-94.
  20. Afzal MS, Akhtar MS, Shahid A, Imran MB, Irfanullah J, Khan MA et al. Pattern of distribution of metastatic lesions within skeleton in patients with breast carcinoma of faisalabad and its vicinity. APMC. 2009;3(1):13-18.
  21. Cook GJR. Imaging of Bone Metastases in Breast cancer. Semin Nucl Med. 2022;52(6):531-541.
  22. Schröder J, Fietz T, Köhler A, Petersen V, Tesch H, Spring L, et al. Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer–Results from the prospective German Tumour Registry Breast Cancer cohort study. 2017;79:139-148.
  23. Suva LJ, Washam C, Nicholas RW, Griffin RJ. Bone metastasis: mechanisms and therapeutic opportunities. Nat Rev Endocrinol. 2011;7(4):208-218.
  24. Wolska J, Wolski D, Stanisławek A, Weber D, Irzmańska-Hudziak Health. Metastasis of breast cancer to the bone. AJJoE. 2019;9(8):905-911.
  25. Pulido C, Vendrell I, Ferreira AR, Casimiro S, Mansinho A, Alho I, et al. Bone metastasis risk factors in breast cancer. Ecancermedicalscience. 2017;11:715.
  26. Buonomo OC, Caredda E, Portarena I, Vanni G, Orlandi A, Bagni C, et al. New insights into the metastatic behavior after breast cancer surgery, according to well-established clinicopathological variables and molecular subtypes. PLoS One. 2017;12(9):e0184680-e.
  27. Molnar IA, Molnar BA, Vizkeleti L, Fekete K, Tamas J, Deak P et al. Breast carcinoma subtypes show different patterns of metastatic behavior. Virchows archive. 2017;470(3): 275–283.
  28. Leone BA, Vallejo CT, Romero AO, Machiavelli MR, Pérez JE, Leone J, et al. Prognostic impact of metastatic pattern in stage IV breast cancer at initial diagnosis. Breast Cancer Res Treat. 2017;161(3):537-548.
  29. Park S, Koo JS, Kim MS, Park HS, Lee JS, Lee JS, et al. Characteristics and outcomes according to molecular subtypes of breast cancer as classified by a panel of four biomarkers using immunohistochemistry. The Breast. 2012;21(6):50-57.
  30. Chen X, Sun L, Cong Y, Zhang T, Lin Q, Meng Q, et al. Baseline staging tests based on molecular subtype is necessary for newly diagnosed breast cancer. J Exp Clin Cancer Res. 2014;33(1):28.
  31. Kim J, Lee Y, Yoo T, Kim J, Hyun J, Park I, et al. Organ-Specific Recurrence or Metastatic Pattern of Breast Cancer according to Biological Subtypes and Clinical Characteristics. J Breast Dis. 2019;7(1):30-37.
  32. Caldeira PRAF, Martinez CAR, Caldeira JRF. Evaluation of Bone Metastasis of Breast Cancer to Long or Short Bones, according to Molecular Subtypes: Retrospective Study. Mastology. 2019;29(1):32-36.
  33. Seshie B, Adu-Aryee NA, Dedey F, Calys-Tagoe B, Clegg-Lamptey J-N. A retrospective analysis of breast cancer subtype based on ER/PR and HER2 status in Ghanaian patients at the Korle Bu Teaching Hospital, Ghana. BMC Clin Pathol. 2015;15:14.
  34. Koo JS, Jung W, Jeong J. Metastatic breast cancer shows different immunohistochemical phenotype according to metastatic site. Tumori. 2010;96(3):424-432.
  35. Park HS, Kim S, Kim K, Yoo H, Chae BJ, Bae JS, et al. Pattern of distant recurrence according to the molecular subtypes in Korean women with breast cancer. World J Surg Oncol. 2012;10:4.
  36. Wu S-G, Sun J-Y, Yang L-C, Tang L-Y, Wang X, Chen X-T, et al. Patterns of distant metastasis in Chinese women according to breast cancer subtypes. Oncotarget. 2016;7(30):47975-47984.
  37. Koizumi M, Yoshimoto M, Kasumi F, Ogata E. Comparison between solitary and multiple skeletal metastatic lesions of breast cancer patients. Ann Oncol. 2003;14(8):1234-40.
How to Cite

Ahmadu, O. T., Umar, S. S., Ahmed, S. A., Liman, A. B., & Mdaka, T. (2025). SCINTIGRAPHIC PATTERN OF SKELETAL METASTASIS BASED ON MOLECULAR SUBTYPES OF BREAST CANCER AT THE DR GEORGE MUKHARI ACADEMIC HOSPITAL GARANKUWA, SOUTH AFRICA. Nigerian Journal of Oncology, 1(1), 60-69. https://doi.org/10.67579/njo.2025.tplwhm7u

O. T. Ahmadu, S. S. Umar, S. A. Ahmed, A. B. Liman, and T. Mdaka, "SCINTIGRAPHIC PATTERN OF SKELETAL METASTASIS BASED ON MOLECULAR SUBTYPES OF BREAST CANCER AT THE DR GEORGE MUKHARI ACADEMIC HOSPITAL GARANKUWA, SOUTH AFRICA," Nigerian Journal of Oncology, vol. 1, no. 1, pp. 60-69, January 2025. doi: 10.67579/njo.2025.tplwhm7u

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