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Central nervous system metastases in breast cancer: the impact of age on patterns of development and outcome

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Abstract

Purpose

The purpose of this study is to explore differences in the pattern and outcome of central nervous system (CNS) involvement in breast cancer by age at diagnosis.

Methods

A retrospective database of a tertiary cancer center yielded 174 consecutive patients with breast cancer who were diagnosed with CNS metastases in 2006–2019. Data on histopathology, characteristics of CNS involvement, treatments, and survival (at three time points during the disease course) were compared between patients aged ≤ 45 and > 45 years. Pearson Chi-square or Fisher exact test and Kaplan–Meier survival curves with log-rank test were used for statistical analyses.

Results

Study population was divided according to age at diagnosis of breast cancer. 65 patients were ≤ 45 years old and 109 patients > 45 years old. The younger group was characterized by longer median overall survival (117.1 months vs 88 months, p = 0.017) and longer interval between breast cancer diagnosis to development of CNS metastases (97.4 months vs 75.9 months, p = 0.026). Median survival after development of CNS disease was not significantly different (18.7 months vs 11.1 months, p = 0.341), although it was significantly longer in younger patients within the subgroup of patients with triple-negative disease (22.5 vs 7.9 months, p = 0.033). There were no between-group differences in number, location, and clinical presentation of CNS metastases or in systemic and CNS-directed treatment approaches.

Conclusion

While the presentation of CNS involvement was similar between the different age groups, younger patients had significantly longer CNS-free interval and longer overall survival, and for the subgroups of triple-negative patients, younger age at breast cancer diagnosis was associated with longer survival after diagnosis of CNS disease.

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References

  1. Leyland-Jones B (2009) Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J Clin Oncol 27:5278–5286. https://doi.org/10.1200/JCO.2008.19.8481

    Article  PubMed  Google Scholar 

  2. Jia J, Yu G, Jian Z, Leiping W, Biyun W, Jun C, Zhimin S, Zhonghua W (2018) Incidence, pattern and prognosis of brain metastases in patients with metastatic triple negative breast cancer. BMC Cancer 18:446. https://doi.org/10.1186/s12885-018-4371-0

    Article  Google Scholar 

  3. Grasslin O, Abdulkarim BS, Coutant C, Huguet F, Gabos Z, Hsu L, Marpeau O, Uzan S, Pusztai L, Strom EA, Hortobagyi GN, Rouzier R, Ibrahim NK (2010) Nomogram to predict subsequent brain metastasis in patients with metastatic breast cancer. J Clin Oncol 28:2032–2037. https://doi.org/10.1200/JCO.2009.24.6314

    Article  Google Scholar 

  4. Sperduto PW, Kased N, Roberge D et al (2012) Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol 30:419–425. https://doi.org/10.1200/JCO.2011.38.0527

    Article  PubMed  Google Scholar 

  5. Kavouridis VK, Harary M, Hulsbergen AFC, Lo YT, Reardon DA, Aizer AA, Iorgulescu JB, Smith TR (2019) Survival and prognostic factors in surgically treated brain metastases. J Neurooncol 143:359–367. https://doi.org/10.1007/s11060-019-03171-6

    Article  CAS  PubMed  Google Scholar 

  6. Ramakrishna N, Temin S, Chandarlapaty S et al (2014) Recommendations on disease management for patients with advanced human epidermal growth factor receptor 2–positive breast cancer and brain metastases: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:2100–2108. https://doi.org/10.1200/JCO.2013.54.0955

    Article  PubMed  PubMed Central  Google Scholar 

  7. Saip P, Cicin I, Eralp Y, Karagol H, Kucucuk S, Cosar Alas R, Yavuz E, Dincer M, Saglam E, Topuz E (2009) Identification of patients who may benefit from the prophylactic cranial radiotherapy among breast cancer patients with brain metastasis. J Neurooncol 93:243–251. https://doi.org/10.1007/s11060-008-9769-0

    Article  PubMed  Google Scholar 

  8. Tomasevic ZI, Rakocevic Z, Tomasevic ZM, Milovanovic Z, Inic M, Kolarevic D, Lukic V, Kovac Z (2012) Incidence of brain metastases in early stage HER2 3+ breast cancer patients: is there a role for brain CT in asymptomatic patients? J BUON 17:249–253

    CAS  PubMed  Google Scholar 

  9. Pestalozzi B, Zahrieh D, Price K, International Breast Cancer Study Group (IBCSG) et al (2006) Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG). Ann Oncol 17:935–944. https://doi.org/10.1093/annonc/mdl064

    Article  CAS  PubMed  Google Scholar 

  10. Lekanidi K, Evans AL, Shah J, Jaspan T, Baker L, Evans AJ (2013) Pattern of brain metastatic disease according to HER-2 and ER receptor status in breast cancer patients. Clin Radiol 68:1070–1073. https://doi.org/10.1016/j.crad.2013.05.091

    Article  CAS  PubMed  Google Scholar 

  11. Maggard MA, O’Connell JB, Ke L, Liu JH, Etzioni DA, Ko CY (2003) Do young breast cancer patients have worst outcome? J Surg Res 13:109–113. https://doi.org/10.1016/s0022-4804(03)00179-3

    Article  Google Scholar 

  12. Lee HB, Han W (2014) Unique features of young age breast cancer and its management. J Breast Cancer 17:301–307. https://doi.org/10.4048/jbc.2014.17.4.301

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wang J, Wang J, Li Q et al (2017) Young breast cancer patients who develop distant metastasis after surgery have better survival outcomes compared to elderly counterparts. Oncotarget 8:44851–44859. https://doi.org/10.18632/oncotarget.15268

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mustillo A, Ayoub J-PM, Yelle L, Florescu M (2018) Prognosis in young women under 40 with brain metastasis from breast cancer. J Clin Oncol 36(15 Suppl):1091

    Article  Google Scholar 

  15. Anders CK, Deal AM, Miller CR, Khorram C, Meng H, Burrows E, Livasy C, Fritchie K, Ewend MG, Perou CM, Carey LA (2010) The prognostic contribution of clinical breast cancer subtype, age and race among patients with breast cancer brain metastases. Cancer 117:1602–1611. https://doi.org/10.1002/cncr.25746

    Article  PubMed  PubMed Central  Google Scholar 

  16. Vrieling C, Collette L, Fourquet A, EORTC Radiotherapy, Breast Cancer Groups et al (2003) Can patient-, treatment-, and pathology-related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients? Eur J Cancer 39:932–944

    Article  CAS  Google Scholar 

  17. Sheridan W, Scott T, Caroline S, Yvonne Z, Vanessa B, David V, Karen G, Stephen C (2014) Breast cancer in young women: have the prognostic implications of breast cancer subtypes changed over time? Breast Cancer Res Treat 147:617–629. https://doi.org/10.1007/s10549-014-3125-1

    Article  PubMed  Google Scholar 

  18. Rudat V, El-Sweilmeen H, Brune EI et al (2014) Identification of breast cancer patients with a high risk of developing brain metastases: a single-institutional retrospective analysis. BMC Cancer 14:289. https://doi.org/10.1186/1471-2407-14-289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 13(15 Pt 1):4429–4434. https://doi.org/10.1158/1078-0432.CCR-06-3045

    Article  PubMed  Google Scholar 

  20. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (ER)negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California Cancer Registry. Cancer 109:1721–1728. https://doi.org/10.1002/cncr.22618

    Article  PubMed  Google Scholar 

  21. McKenzie HS, Maishman T, Simmonds P, Durcan L et al (2020) Survival and disease characteristics of de novo versus recurrent metastatic breast cancer in a cohort of young patients. Br J Cancer 122:1618–1629. https://doi.org/10.1038/s41416-020-0784-z

    Article  PubMed  Google Scholar 

  22. Dolle JM, Daling JR, White E, Brinton LA, Doody DR, Porter PL, Malone KE (2009) Risk factors for triple-negative breast cancer in women under the age of 45 years. Cancer Epidemiol Biomarkers Prev 18:1157–1166. https://doi.org/10.1158/1055-9965.EPI-08-1005

    Article  PubMed  PubMed Central  Google Scholar 

  23. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655

    Article  CAS  Google Scholar 

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Funding

No funding was received for this study.

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Authors and Affiliations

  1. Davidoff Cancer Center, Rabin Medical Center–Beilinson Hospital, 4941492, Petach Tikva, Israel

    Matan Ben-Zion Berliner, Rinat Yerushalmi, Alexandra Benouaich-Amiel, Daliah Tsoref, Daniel Hendler, Hadar Goldvaser, Michal Sarfaty, Ofer Rotem, Olga Ulitsky, Tali Siegal, Victoria Neiman & Shlomit Yust-Katz

  2. Sackler Faculty of Medicine, Tel Aviv, Israel

    Rinat Yerushalmi, Inbar Lavie‏, Daliah Tsoref, Michal Sarfaty & Shlomit Yust-Katz

Authors
  1. Matan Ben-Zion Berliner
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  2. Rinat Yerushalmi
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  3. Inbar Lavie‏
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  4. Alexandra Benouaich-Amiel
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  5. Daliah Tsoref
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  6. Daniel Hendler
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  8. Michal Sarfaty
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  11. Tali Siegal
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  12. Victoria Neiman
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  13. Shlomit Yust-Katz
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Correspondence to Matan Ben-Zion Berliner.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the local institute Helsinki committee of Rabin Medical Center.

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Ben-Zion Berliner, M., Yerushalmi, R., Lavie‏, I. et al. Central nervous system metastases in breast cancer: the impact of age on patterns of development and outcome. Breast Cancer Res Treat 185, 423–432 (2021). https://doi.org/10.1007/s10549-020-05959-x

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  • DOI: https://doi.org/10.1007/s10549-020-05959-x

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