BONE METASTASES OF BREAST CANCER – THE INFLUENCE OF HORMONE AND HER2 RECEPTORS

  • Stanislav Rajković Univerzitet u Beogradu, Medicinski fakultet, Institut za ortopediju "Banjica", Beograd, Srbija
Keywords: Breast cancer, Metastasis, Bone metastases, Hormone receptors, HER2

Abstract


Breast cancer is the leading cause of cancer-related deaths among women worldwide. While significant progress has been made in the prophylaxis, diagnosis, and management of breast cancer, around 90% of deaths occur due to metastatic disease, which is still incurable. The bone has been identified as one of the predominant metastatic sites, accounting for around 80% of patients with metastatic breast cancer. The paper aims to summarize the hallmarks of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) influence on breast cancer bone metastases development and their further biological and clinical behavior.

Various clinicopathological characteristics have been identified as risk factors for the development of metastases. In particular, the status of ER, PR and HER2 is crucial for making clinical decisions as an important tool for predicting the spread of breast cancer and choosing a therapeutic protocol. Patients with any hormone receptor positive status, particularly those with ER+, PR+/HER2-, are more likely to develop bone-only-metastatic (BOM), whereas those with hormone receptor negative status, especially those with so-called triple-negative (HR-/HER2-) or HER2+ breast cancer, have a predilection for visceral metastases. The paper highlights that while bone metastases of breast cancer are much less investigated than primary tumors, more studies are needed to understand the complex, multi-step process involved in the development and behavior of bone metastases.

References

1.         Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, Wei S. Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol. 2015 Apr;143(4):471-8. doi: 10.1309/AJCPYO5FSV3UPEXS.


2.         Gentile M, Centonza A, Lovero D, Palmirotta R, Porta C, Silvestris F, et al. Application of "omics" sciences to the prediction of bone metastases from breast cancer: State of the art. J Bone Oncol. 2020 Nov 5;26:100337. doi: 10.1016/j.jbo.2020.100337.


3.         Harries M, Taylor A, Holmberg L, Agbaje O, Garmo H, Kabilan S, et al. Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients. Cancer Epidemiol. 2014 Aug;38(4):427-34. doi: 10.1016/j.canep.2014.05.005.


4.         Schröder J, Fietz T, Köhler A, Petersen V, Tesch H, Spring L, et al; TMK-Group (Tumour Registry Breast Cancer). Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer - Results from the prospective German Tumour Registry Breast Cancer cohort study. Eur J Cancer. 2017 Jul;79:139-148. doi: 10.1016/j.ejca.2017.03.031.


5.         Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, et al. Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol. 2015 Apr;143(4):471-8. doi: 10.1309/AJCPYO5FSV3UPEXS.


6.         Zhang L, Zhang J, Li Z, Wu Y, Tong Z. Comparison of the clinicopathological characteristics and prognosis between Chinese patients with breast cancer with bone-only and non-bone-only metastasis. Oncol Lett. 2020 Oct;20(4):92. doi: 10.3892/ol.2020.11953.


7.         Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, et al. Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol. 2015 Apr;143(4):471-8. doi: 10.1309/AJCPYO5FSV3UPEXS.


8.         Colleoni M, O'Neill A, Goldhirsch A, Gelber RD, Bonetti M, Thürlimann B, et al. Identifying breast cancer patients at high risk for bone metastases. J Clin Oncol. 2000 Dec 1;18(23):3925-35. doi: 10.1200/JCO.2000.18.23.3925.


9.         Jones DH, Nakashima T, Sanchez OH, Kozieradzki I, Komarova SV, Sarosi I, et al. Regulation of cancer cell migration and bone metastasis by RANKL. Nature. 2006 Mar 30;440(7084):692-6. doi: 10.1038/nature04524.


10.       Meng F, Wu G. The rejuvenated scenario of epithelial-mesenchymal transition (EMT) and cancer metastasis. Cancer Metastasis Rev. 2012 Dec;31(3-4):455-67. doi: 10.1007/s10555-012-9379-3.


11.       Sharma B, Nannuru KC, Saxena S, Varney ML, Singh RK. CXCR2: A Novel Mediator of Mammary Tumor Bone Metastasis. Int J Mol Sci. 2019 Mar 12;20(5):1237. doi: 10.3390/ijms20051237.


12.       Zeng J, Piscuoglio S, Aggarwal G, Magda J, Friedlander MA, Murray M, et al. Hormone receptor and HER2 assessment in breast carcinoma metastatic to bone: A comparison between FNA cell blocks and decalcified core needle biopsies. Cancer Cytopathol. 2020 Feb;128(2):133-145. doi: 10.1002/cncy.22226.


13.       Hammond ME, Hayes DF, Wolff AC. Clinical Notice for American Society of Clinical Oncology-College of American Pathologists guideline recommendations on ER/PgR and HER2 testing in breast cancer. J Clin Oncol. 2011 May 20;29(15):e458. doi: 10.1200/JCO.2011.35.2245.


14.       Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, et al. American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010 Jun 1;28(16):2784-95. doi: 10.1200/JCO.2009.25.6529.


15.       Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. American Society of Clinical Oncology; College of American Pathologists. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013 Nov 1;31(31):3997-4013. doi: 10.1200/JCO.2013.50.9984.


16.       Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010 Apr 1;28(10):1684-91. doi: 10.1200/JCO.2009.24.9284.


17.       Diessner J, Wischnewsky M, Stüber T, Stein R, Krockenberger M, Häusler S, et al. Evaluation of clinical parameters influencing the development of bone metastasis in breast cancer. BMC Cancer. 2016 May 12;16:307. doi: 10.1186/s12885-016-2345-7.


18.       Zhang H, Zhu W, Biskup E, Yang W, Yang Z, Wang H, et al. Incidence, risk factors and prognostic characteristics of bone metastases and skeletal-related events (SREs) in breast cancer patients: A systematic review of the real world data. J Bone Oncol. 2018 Feb 3;11:38-50. doi: 10.1016/j.jbo.2018.01.004.


19.       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 Jan 8;10:4. doi: 10.1186/1477-7819-10-4.


20.       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 Feb;161(3):537-548. doi: 10.1007/s10549-016-4066-7.


21.       Soni A, Ren Z, Hameed O, Chanda D, Morgan CJ, Siegal GP, et al. Breast cancer subtypes predispose the site of distant metastases. Am J Clin Pathol. 2015 Apr;143(4):471-8. doi: 10.1309/AJCPYO5FSV3UPEXS.


22.       Metzger-Filho O, Sun Z, Viale G, Price KN, Crivellari D, Snyder RD, et al. Patterns of Recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international breast cancer study group trials VIII and IX. J Clin Oncol. 2013 Sep 1;31(25):3083-90. doi: 10.1200/JCO.2012.46.1574.


23.       Belzarena AC, Binitie O, Letson D, Joyce DM. Intramedullary rod failure in metastatic breast cancer: Do triple negative cancer patients have more revision surgery? J Bone Oncol. 2021 Apr 1;28:100358. doi: 10.1016/j.jbo.2021.100358.


24.       Rakha EA, El-Sayed ME, Green AR, Paish EC, Powe DG, Gee J, et al. Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype. J Clin Oncol. 2007 Oct 20;25(30):4772-8. doi: 10.1200/JCO.2007.12.2747.


25.       Bae SY, Kim S, Lee JH, Lee HC, Lee SK, Kil WH, et al. Poor prognosis of single hormone receptor- positive breast cancer: similar outcome as triple-negative breast cancer. BMC Cancer. 2015 Mar 18;15:138. doi: 10.1186/s12885-015-1121-4.


26.       Shen T, Brandwein-Gensler M, Hameed O, Siegal GP, Wei S. Characterization of estrogen receptor-negative/progesterone receptor-positive breast cancer. Hum Pathol. 2015 Nov;46(11):1776-84. doi: 10.1016/j.humpath.2015.07.019.


27.       Zhao H, Gong Y. The Prognosis of Single Hormone Receptor-Positive Breast Cancer Stratified by HER2 Status. Front Oncol. 2021 May 17;11:643956. doi: 10.3389/fonc.2021.643956.


28.       Manders K, van de Poll-Franse LV, Creemers GJ, Vreugdenhil G, van der Sangen MJ, Nieuwenhuijzen GA, et al. Clinical management of women with metastatic breast cancer: a descriptive study according to age group. BMC Cancer. 2006 Jul 6;6:179. doi: 10.1186/1471-2407-6-179.


29.       Brennan MJ, Donegan WL, Appleby DE. The variability of estrogen receptors in metastatic breast cancer. Am J Surg. 1979 Feb;137(2):260-2. doi: 10.1016/0002-9610(79)90159-4.


30.       Holdaway IM, Bowditch JV. Variation in receptor status between primary and metastatic breast cancer. Cancer. 1983 Aug 1;52(3):479-85. doi: 10.1002/1097-0142(19830801)52:3<479::aid-cncr2820520317>3.0.co;2-o.


31.       Lindström LS, Karlsson E, Wilking UM, Johansson U, Hartman J, Lidbrink EK, et al. Clinically used breast cancer markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 are unstable throughout tumor progression. J Clin Oncol. 2012 Jul 20;30(21):2601-8. doi: 10.1200/JCO.2011.37.2482.


32.       Lindstrom L, Howell S, Astrom G, et al. Controversies in the management of metastatic breast cancer: biologic evaluation of breast cancer–should metastases be biopsied? In: American Society of Clinical Oncology 2010 Educational Book. American Society of Clinical Oncology; 2010:e7-e12.


33.       Hou Y, Shen R, Chaudhary S, Gao F, Li Z. Correlation of Expression of Breast Biomarkers in Primary and Metastatic Breast Carcinomas: A Single-Institution Experience. Acta Cytol. 2016;60(5):481-489. doi: 10.1159/000449400. Epub 2016 Sep 29.


34.       Zeng J, Piscuoglio S, Aggarwal G, Magda J, Friedlander MA, Murray M, et al. Hormone receptor and HER2 assessment in breast carcinoma metastatic to bone: A comparison between FNA cell blocks and decalcified core needle biopsies. Cancer Cytopathol. 2020 Feb;128(2):133-145. doi: 10.1002/cncy.22226. Epub 2019 Dec 28.


35.       Kao JY, Tsai JH, Wu TY, Wang CK, Kuo YL. Receptor discordance and phenotype change in metastatic breast cancer. Asian J Surg. 2021 Jan;44(1):192-198. doi: 10.1016/j.asjsur.2020.05.032.


36.       Van Poznak C, Somerfield MR, Bast RC, Cristofanilli M, Goetz MP, Gonzalez-Angulo AM, et al. Use of Biomarkers to Guide Decisions on Systemic Therapy for Women With Metastatic Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2015 Aug 20;33(24):2695-704. doi: 10.1200/JCO.2015.61.1459.


37.       Lin J, Goldstein L, Nesbit A, Chen MY. Influence of Hormone Receptor Status on Spinal Metastatic Lesions in Patients with Breast Cancer. World Neurosurg. 2016 Jan;85:42-8. doi: 10.1016/j.wneu.2015.07.068.


38.       Kozlow W, Guise TA. Breast cancer metastasis to bone: mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia. 2005 Apr;10(2):169-80. doi: 10.1007/s10911-005-5399-8.


39.       Hadjidakis DJ, Androulakis II. Bone remodeling. Ann N Y Acad Sci. 2006 Dec;1092:385-96. doi: 10.1196/annals.1365.035.


40.       von Moos R, Body JJ, Egerdie B, Stopeck A, Brown J, Fallowfield L, et al. Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases. Support Care Cancer. 2016 Mar;24(3):1327-37. doi: 10.1007/s00520-015-2908-1.


41.       Sathiakumar N, Delzell E, Morrisey MA, Falkson C, Yong M, Chia V, et al. Mortality following bone metastasis and skeletal-related events among women with breast cancer: a population-based analysis of U.S. Medicare beneficiaries, 1999-2006. Breast Cancer Res Treat. 2012 Jan;131(1):231-8. doi: 10.1007/s10549-011-1721-x.


42.       Wedin R, Skoog L, Bauer HC. Proliferation rate, hormone receptor status and p53 expression in skeletal metastasis of breast carcinoma. Acta Oncol. 2004;43(5):460-6. doi: 10.1080/02841860410033721.


43.       Shen T, Brandwein-Gensler M, Hameed O, Siegal GP, Wei S. Characterization of estrogen receptor-negative/progesterone receptor-positive breast cancer. Hum Pathol. 2015 Nov;46(11):1776-84. doi: 10.1016/j.humpath.2015.07.019.


44.       Li Z, Wei H, Li S, Wu P, Mao X. The Role of Progesterone Receptors in Breast Cancer. Drug Des Devel Ther. 2022 Jan 26;16:305-314. doi: 10.2147/DDDT.S336643.

Published
2024/05/08
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