Bone Marrow Infiltration in Breast Cancer: Diagnostic and Prognostic Perspectives- A Narrative Review

Emmanuel Ifeanyi Obeagu; Bibek  Giri

doi:10.22270/ijmspr.v12i3.199

Authors

Emmanuel Ifeanyi Obeagu Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe https://orcid.org/0000-0002-4538-0161
Bibek Giri Research Institute for Collaborative Development, Kathmandu, Nepal.

DOI:

https://doi.org/10.22270/ijmspr.v12i3.199

Keywords:

Bone marrow infiltration, breast cancer, metastasis, diagnostic methods, prognostic markers

Abstract

Bone marrow infiltration (BMI) by breast cancer cells is an early and critical step in the metastatic cascade that significantly impacts patient prognosis. The bone marrow microenvironment serves as a sanctuary for disseminated tumor cells, allowing them to survive, evade treatment, and potentially lead to disease recurrence. Understanding the mechanisms and clinical significance of BMI is essential for improving detection and therapeutic strategies in breast cancer management. Diagnostic approaches for identifying BMI range from invasive techniques such as bone marrow biopsy with histopathological and immunocytochemical analysis, to emerging molecular assays that increase sensitivity for detecting isolated tumor cells. Conventional imaging modalities provide limited sensitivity for early marrow involvement, underscoring the need for more precise diagnostic tools. Advances in molecular diagnostics and liquid biopsy technologies hold promise for less invasive and more accurate detection of bone marrow micro metastases. The presence of BMI in breast cancer patients is strongly associated with poorer outcomes, including increased risk of relapse and reduced overall survival. As a marker of minimal residual disease, BMI assessment can inform prognosis and guide personalized treatment decisions, including the escalation of adjuvant therapies. Integrating bone marrow evaluation into clinical practice and further elucidating tumor-microenvironment interactions could enhance metastasis prevention and improve long-term patient outcomes.

Keywords: Bone marrow infiltration, breast cancer, metastasis, diagnostic methods, prognostic markers

Author Biographies

Emmanuel Ifeanyi Obeagu , Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe

Department of Biomedical and Laboratory Science, Africa University, Mutare, Zimbabwe

Bibek Giri , Research Institute for Collaborative Development, Kathmandu, Nepal.

Research Institute for Collaborative Development, Kathmandu, Nepal.

References

World Health Organization. Breast cancer.: W.H.O.; 2025 [cited 2025 october 16]. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer.

Yu J, Mu Q, Fung M, Xu X, Zhu L, Ho RJY. Challenges and opportunities in metastatic breast cancer treatments: Nano-drug combinations delivered preferentially to metastatic cells may enhance therapeutic response. Pharmacol Ther. 2022;236:108108. PMid:34999182 PMCid:PMC9256851 https://doi.org/10.1016/j.pharmthera.2022.108108

Pang L, Gan C, Xu J, Jia Y, Chai J, Huang R, et al. Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies. Cancers (Basel). 2022;14(23). PMid:36497209 PMCid:PMC9738274 https://doi.org/10.3390/cancers14235727

Hofbauer LC, Bozec A, Rauner M, Jakob F, Perner S, Pantel K. Novel approaches to target the microenvironment of bone metastasis. Nature reviews Clinical oncology. 2021;18(8):488-505. https://doi.org/10.1038/s41571-021-00499-9 PMid:33875860

Krishnamurthy S, Cristofanilli M, Singh B, Reuben J, Gao H, Cohen EN, et al. Detection of minimal residual disease in blood and bone marrow in early stage breast cancer. Cancer. 2010;116(14):3330-3337. https://doi.org/10.1002/cncr.25145 PMid:20564098

Chen F, Han Y, Kang Y. Bone marrow niches in the regulation of bone metastasis. British Journal of Cancer. 2021;124(12):1912-1920. https://doi.org/10.1038/s41416-021-01329-6 PMid:33758331 PMCid:PMC8184962

Wieder R. Awakening of dormant breast cancer cells in the bone marrow. Cancers. 2023;15(11):3021. PMid:37296983 PMCid:PMC10252003 https://doi.org/10.3390/cancers15113021

Vincent-Salomon A, Bidard F-C, Pierga J-Y. Bone marrow micrometastasis in breast cancer: review of detection methods, prognostic impact and biological issues. Journal of clinical pathology. 2008;61(5):570-576. PMid:18037661 PMCid:PMC2564844 https://doi.org/10.1136/jcp.2007.046649

Tomasian A, Jennings JW. Bone marrow aspiration and biopsy: techniques and practice implications. Skeletal Radiology. 2022;51(1):81-88. https://doi.org/10.1007/s00256-021-03882-w PMid:34398308

Baker M, Gillanders WE, Mikhitarian K, Mitas M, Cole DJ. The molecular detection of micrometastatic breast cancer. The American journal of surgery. 2003;186(4):351-358. https://doi.org/10.1016/S0002-9610(03)00262-9

Kamińska P, Buszka K, Zabel M, Nowicki M, Alix-Panabieres C, Budna-Tukan J. Liquid biopsy in melanoma: significance in diagnostics, prediction and treatment monitoring. International Journal of Molecular Sciences. 2021;22(18):9714. https://doi.org/10.3390/ijms22189714 PMid:34575876

Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, et al. A pooled analysis of bone marrow micrometastasis in breast cancer. New England journal of medicine. 2005;353(8):793-802. https://doi.org/10.1056/NEJMoa050434 PMid:16120859

Janni W, Vogl FD, Wiedswang G, Synnestvedt M, Fehm T, Jückstock J, et al. Persistence of disseminated tumor cells in the bone marrow of breast cancer patients predicts increased risk for relapse-a European pooled analysis. Clinical Cancer Research. 2011;17(9):2967-2976. https://doi.org/10.1158/1078-0432.CCR-10-2515 PMid:21415211

Hartkopf AD, Taran F-A, Wallwiener M, Hahn M, Becker S, Solomayer E-F, et al. Prognostic relevance of disseminated tumour cells from the bone marrow of early stage breast cancer patients-results from a large single-centre analysis. European journal of cancer. 2014;50(15):2550-2559. https://doi.org/10.1016/j.ejca.2014.06.025 PMid:25096167

Massagué J, Obenauf AC. Metastatic colonization by circulating tumour cells. Nature. 2016;529(7586):298-306. https://doi.org/10.1038/nature17038 PMid:26791720 PMCid:PMC5029466

Weilbaecher KN, Guise TA, McCauley LK. Cancer to bone: a fatal attraction. Nature Reviews Cancer. 2011;11(6):411-425. https://doi.org/10.1038/nrc3055 PMid:21593787 PMCid:PMC3666847

Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G, et al. Pre-metastatic niches: organ-specific homes for metastases. Nature Reviews Cancer. 2017;17(5):302-317. https://doi.org/10.1038/nrc.2017.6 PMid:28303905

Wang H, Tian L, Liu J, Goldstein A, Bado I, Zhang W, et al. The osteogenic niche is a calcium reservoir of bone micrometastases and confers unexpected therapeutic vulnerability. Cancer cell. 2018;34(5):823-839. e7. PMid:30423299 PMCid:PMC6239211 https://doi.org/10.1016/j.ccell.2018.10.002

Eiro N, Gonzalez LO, Fraile M, Cid S, Schneider J, Vizoso FJ. Breast cancer tumor stroma: cellular components, phenotypic heterogeneity, intercellular communication, prognostic implications and therapeutic opportunities. Cancers. 2019;11(5):664. https://doi.org/10.3390/cancers11050664 PMid:31086100 PMCid:PMC6562436

Gomis RR, Gawrzak S. Tumor cell dormancy. Molecular oncology. 2017;11(1):62-78. PMid:28017284 PMCid:PMC5423221 https://doi.org/10.1016/j.molonc.2016.09.009

Croucher PI, McDonald MM, Martin TJ. Bone metastasis: the importance of the neighbourhood. Nature Reviews Cancer. 2016;16(6):373-86. https://doi.org/10.1038/nrc.2016.44 PMid:27220481

Sceneay J, Smyth MJ, Möller A. The pre-metastatic niche: finding common ground. Cancer and Metastasis Reviews. 2013;32(3):449-464. https://doi.org/10.1007/s10555-013-9420-1 PMid:23636348

Borgen E, Naume B, Nesland J, Kvalheim G, Beiske K, Fodstad Ø, et al. Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy. 1999;1(5):377-388. PMid:20426539 https://doi.org/10.1080/0032472031000141283

Pantel K, Alix-Panabières C. Liquid biopsy and minimal residual disease-latest advances and implications for cure. Nature Reviews Clinical Oncology. 2019;16(7):409-424. https://doi.org/10.1038/s41571-019-0187-3 PMid:30796368

Hartkopf AD, Brucker SY, Taran FA, Harbeck N, von Au A, Naume B, et al. Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis. Eur J Cancer. 2021;154:128-137. https://doi.org/10.1016/j.ejca.2021.06.028 PMid:34265505

Riedl CC, Pinker K, Ulaner GA, Ong LT, Baltzer P, Jochelson MS, et al. Comparison of FDG-PET/CT and contrast-enhanced CT for monitoring therapy response in patients with metastatic breast cancer. European journal of nuclear medicine and molecular imaging. 2017;44(9):1428-1437. PMCid:PMC5526620 https://doi.org/10.1007/s00259-017-3703-7

Ulaner GA, Silverstein M, Nangia C, Tetef M, Vandermolen L, Coleman C, et al. ER-Targeted PET for Initial Staging and Suspected Recurrence in ER-Positive Breast Cancer. JAMA Netw Open. 2024;7(7):e2423435. PMCid:PMC11282447 https://doi.org/10.1001/jamanetworkopen.2024.23435

Cristofanilli M, Pierga J-Y, Reuben J, Rademaker A, Davis AA, Peeters DJ, et al. The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper. Critical reviews in oncology/hematology. 2019;134:39-45. PMid:30771872 https://doi.org/10.1016/j.critrevonc.2018.12.004

Ignatiadis M, Lee M, Jeffrey SS. Circulating tumor cells and circulating tumor DNA: challenges and opportunities on the path to clinical utility. Clinical Cancer Research. 2015;21(21):4786-4800. https://doi.org/10.1158/1078-0432.CCR-14-1190 PMid:26527805

Janni WJ, Rack B, Terstappen LW, Pierga JY, Taran FA, Fehm T, et al. Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer. Clin Cancer Res. 2016;22(10):2583-2593. https://doi.org/10.1158/1078-0432.CCR-15-1603 PMid:26733614 PMCid:PMC10670968

Coleman R. Bone-Targeted Agents and Metastasis Prevention. Cancers (Basel). 2022;14(15). PMid:35892899 PMCid:PMC9367604 https://doi.org/10.3390/cancers14153640

Coombes RC, Page K, Salari R, Hastings RK, Armstrong A, Ahmed S, et al. Personalized Detection of Circulating Tumor DNA Antedates Breast Cancer Metastatic Recurrence. Clin Cancer Res. 2019;25(14):4255-4263. https://doi.org/10.1158/1078-0432.CCR-18-3663 PMid:30992300 PMCid:PMC10670968