Skip to main content

Advertisement

Log in

Systemic inflammation in older patients with breast cancer: the missing point in geriatric evaluations to sharpen survival prediction

  • Research Article
  • Published:
Clinical and Translational Oncology Aims and scope Submit manuscript

Abstract

Background

Breast cancer (BC) prevalence steadily increases in older patients but their treatment is based on the geriatric evaluations of comorbidities and potential benefits proved in clinical trials with younger patients. The lack of better decision-making tools urges to promote the search for new prognostic markers. The association between inflammation, aging and cancer may be crucial for better treatment selection. We sought to analyze its impact on the survival of older BC patients, evaluating the interaction with age and comorbidities.

Methods

We evaluated the relationship between inflammatory biomarkers at BC diagnosis (circulating blood cell counts and inflammatory indexes) and BC-related and not related mortality rate, evaluating the influence of comorbidities and age through the competitive risks assessment.

Results

We analyzed 148 consecutive BC patients aged ≥ 70 years old, diagnosed with BC and regional lymph node metastases. After the median follow-up of 51.5 months, 59 patients died (28 due to breast cancer progression and 31 because of other causes). Increased levels of circulating monocytes, neutrophils and neutrophil-to-lymphocytes ratio and decreased level of eosinophils and eosinophil multiple by neutrophils-to-lymphocytes ratio were associated with higher probability of BC-related death but not with death related to other causes.

Conclusion

Our data suggest a role of inflammatory parameters as a possible prognostic tool in therapeutic decision-making process in older patients with BC, as increased level of inflammation was associated with cancer-specific mortality. Prospective studies may give the possibility of refining the geriatric evaluation for BC treatment in elderly.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Hurria A, Wong FL, Villaluna D, et al. Role of age and health in treatment recommendations for older adults with breast cancer: the perspective of oncologists and primary care providers. J Clin Oncol. 2008;26(33):5386–92. https://doi.org/10.1200/JCO.2008.17.6891.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Magnuson A, Sedrak MS, Gross CP, et al. Development and validation of a risk tool for predicting severe toxicity in older adults receiving chemotherapy for early-stage breast cancer. J Clin Oncol. 2021. https://doi.org/10.1200/JCO.20.02063.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Bastiaannet E, Portielje JE, van de Velde CJ, et al. Lack of survival gain for elderly women with breast cancer. Oncologist. 2011;16(4):415–23. https://doi.org/10.1634/theoncologist.2010-0234.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Truffi M, Piccotti F, Albasini S, Tibollo V, Morasso CF, Sottotetti F, Corsi F. Preoperative systemic inflammatory biomarkers are independent predictors of disease recurrence in ER+ HER2-early breast cancer. Front Oncol. 2021;11: 773078. https://doi.org/10.3389/fonc.2021.773078.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Franceschi C, Bonafè M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54. https://doi.org/10.1111/j.1749-6632.2000.tb06651.x.

    Article  CAS  PubMed  Google Scholar 

  6. Jenny NS. Inflammation in aging: cause, effect, or both? Discov Med. 2012;13(73):451–60.

    PubMed  Google Scholar 

  7. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94(446):496–509. https://doi.org/10.2307/2670170.

    Article  Google Scholar 

  8. Noordzij M, Leffondré K, van Stralen KJ, Zoccali C, Dekker FW, Jager KJ. When do we need competing risks methods for survival analysis in nephrology? Nephrol Dial Transplant. 2013;28(11):2670–7. https://doi.org/10.1093/ndt/gft355.

    Article  PubMed  Google Scholar 

  9. Cappellani A, Di Vita M, Zanghì A, Cavallaro A, Piccolo G, Majorana M, Barbera G, Berretta M. Prognostic factors in elderly patients with breast cancer. BMC Surg. 2013;13(Suppl 2):S2. https://doi.org/10.1186/1471-2482-13-S2-S2.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Biganzoli L, Battisti NML, Wildiers H, et al. Updated recommendations regarding the management of older patients with breast cancer: a joint paper from the European Society of Breast Cancer Specialists (EUSOMA) and the International Society of Geriatric Oncology (SIOG). Lancet Oncol. 2021;22(7):e327–40. https://doi.org/10.1016/S1470-2045(20)30741-5.

    Article  PubMed  Google Scholar 

  11. August DA, Rea T, Sondak VK. Age-related differences in breast cancer treatment. Ann Surg Oncol. 1994;1(1):45–52. https://doi.org/10.1007/BF02303540.

    Article  CAS  PubMed  Google Scholar 

  12. Losada B, Guerra JA, Malón D, Jara C, Rodriguez L, Del Barco S. Pretreatment neutrophil/lymphocyte, platelet/lymphocyte, lymphocyte/monocyte, and neutrophil/monocyte ratios and outcome in elderly breast cancer patients. Clin Transl Oncol. 2019;21(7):855–63. https://doi.org/10.1007/s12094-018-1999-9.

    Article  CAS  PubMed  Google Scholar 

  13. Dillon J, Thomas SM, Rosenberger LH, DiLalla G, Fayanju OM, Menendez CS, Hwang ES, Plichta JK. Mortality in older patients with breast cancer undergoing breast surgery: how low is “Low Risk”? Ann Surg Oncol. 2021;28(10):5758–67. https://doi.org/10.1245/s10434-021-10502-3.

    Article  PubMed  Google Scholar 

  14. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–217. https://doi.org/10.1016/j.cell.2013.05.039.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Fulop T, McElhaney J, Pawelec G, et al. Frailty, inflammation and immunosenescence. Interdiscip Top Gerontol Geriatr. 2015;41:26–40. https://doi.org/10.1159/000381134.

    Article  PubMed  Google Scholar 

  16. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009;30(7):1073–81. https://doi.org/10.1093/carcin/bgp127.

    Article  CAS  PubMed  Google Scholar 

  17. Leng SX, Xue QL, Tian J, et al. Associations of neutrophil and monocyte counts with frailty in community-dwelling disabled older women: results from the Women’s Health and Aging Studies I. Exp Gerontol. 2009;44(8):511–6. https://doi.org/10.1016/j.exger.2009.05.005.

    Article  PubMed  Google Scholar 

  18. Samson LD, Boots AMH, Verschuren WMM, et al. Frailty is associated with elevated CRP trajectories and higher numbers of neutrophils and monocytes. Exp Gerontol. 2019;125: 110674. https://doi.org/10.1016/j.exger.2019.110674.

    Article  CAS  PubMed  Google Scholar 

  19. Szor DJ, Dias AR, Pereira MA, Ramos MFKP, Zilberstein B, Cecconello I, Ribeiro-Júnior U. Prognostic role of neutrophil/lymphocyte ratio in resected gastric cancer: a systematic review and meta-analysis. Clinics (Sao Paulo). 2018;73: e360. https://doi.org/10.6061/clinics/2018/e360.

    Article  Google Scholar 

  20. Shen J, Zhu Y, Wu W, Zhang L, Ju H, Fan Y, Zhu Y, Luo J, Liu P, Zhou N, Lu K, Zhang N, Li D, Liu L. Prognostic role of neutrophil-to-lymphocyte ratio in locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy. Med Sci Monit. 2017;23:315–24. https://doi.org/10.12659/msm.902752.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hanna M, Dumas I, Orain M, Jacob S, Têtu B, Sanschagrin F, Bureau A, Poirier B, Diorio C. Association between local inflammation and breast tissue age-related lobular involution among premenopausal and postmenopausal breast cancer patients. PLoS One. 2017;12(8): e0183579. https://doi.org/10.1371/journal.pone.0183579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Marín Hernández C, Piñero Madrona A, Gil Vázquez PJ, Galindo Fernández PJ, Ruiz Merino G, Alonso Romero JL, Parrilla PP. Usefulness of lymphocyte-to-monocyte, neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios as prognostic markers in breast cancer patients treated with neoadjuvant chemotherapy. Clin Transl Oncol. 2018;20(4):476–83. https://doi.org/10.1007/s12094-017-1732-0.

    Article  PubMed  Google Scholar 

  23. Graziano V, Grassadonia A, Iezzi L, Vici P, Pizzuti L, Barba M, Quinzii A, Camplese A, Di Marino P, Peri M, Veschi S, Alberti S, Gamucci T, Di Gioacchino M, De Tursi M, Natoli C, Tinari N. Combination of peripheral neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio is predictive of pathological complete response after neoadjuvant chemotherapy in breast cancer patients. Breast. 2019;44:33–8. https://doi.org/10.1016/j.breast.2018.12.014.

    Article  PubMed  Google Scholar 

  24. Mccoy JL, Rucker R, Petros JA. Cell-mediated immunity to tumor-associated antigens is a better predictor of survival in early stage breast cancer than stage, grade or lymph node status. Breast Cancer Res Treat. 2000;60(3):227–34. https://doi.org/10.1023/a:1006405504158.

    Article  CAS  PubMed  Google Scholar 

  25. Donskov F, Hokland M, Marcussen N, Torp Madsen HH, von der Maase H. Monocytes and neutrophils as “bad guys” for the outcome of interleukin-2 with and without histamine in metastatic renal cell carcinoma-results from a randomised phase II trial. Br J Cancer. 2006;94(2):218–26. https://doi.org/10.1038/sj.bjc.6602937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wang YH, Shen CY, Lin SC, Kuo WH, Kuo YT, Hsu YL, Wang WC, Lin KT, Wang LH. Monocytes secrete CXCL7 to promote breast cancer progression. Cell Death Dis. 2021;12(12):1090. https://doi.org/10.1038/s41419-021-04231-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39–51. https://doi.org/10.1016/j.cell.2010.03.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fabbri F, Salvi S, Bravaccinni S. Know your enemy: Genetics, aging, exposomic and inflammation in the war against triple negative breast cancer. Semin Cancer Biol. 2020;2(60):285–93. https://doi.org/10.1016/j.semcancer.2019.10.015.

    Article  CAS  Google Scholar 

  29. Carretero R, Sektioglu IM, Garbi N, Salgado OC, Beckhove P, Hämmerling GJ. Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8(+) T cells. Nat Immunol. 2015;16(6):609–17. https://doi.org/10.1038/ni.3159.

    Article  CAS  PubMed  Google Scholar 

  30. Louwman WJ, Janssen-Heijnen ML, Houterman S, Voogd AC, van der Sangen MJ, Nieuwenhuijzen GA, Coebergh JW. Less extensive treatment and inferior prognosis for breast cancer patient with comorbidity: a population-based study. Eur J Cancer. 2005;41(5):779–85. https://doi.org/10.1016/j.ejca.2004.12.025.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Mr Manuel Rain Montecinos for his generous and dedicated contribution to the statistical analysis. The authors wish also to sincerely thank Miss Joselyn Maturana, Dra. Paula Escobar, Dr. Pedro Galaz, Dr Jorge Gamboa, Dr Rodrigo Iglesis, Dr Joaquín Irarrázabal, Dr Miguel Maturana, Dr Aliro Neira and Dra Karina Peña, without their valuable support this study could not have been accomplished.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Andrés Vargas.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The manuscript does not contain clinical studies or patients’ data.

Informed consent

For this type of study, formal consent is not required.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vargas, A., Holub, K. & Biete, A. Systemic inflammation in older patients with breast cancer: the missing point in geriatric evaluations to sharpen survival prediction. Clin Transl Oncol 24, 1800–1808 (2022). https://doi.org/10.1007/s12094-022-02836-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12094-022-02836-5

Keywords

Navigation