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Prognosis and Chemotherapy Use in Breast Cancer Patients with Multiple Lymphatic Micrometastases: An NCDB Analysis

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The number of involved lymph nodes negatively affects prognosis in breast cancer patients. Nevertheless, current staging and treatment recommendations do not distinguish between patients with single versus multiple lymphatic micrometastases. In this study, we aim to better characterize these patients.

Methods

The National Cancer Database was retrospectively queried to identify 486,800 women with stage I–III, estrogen receptor-positive/progesterone receptor-positive/human epidermal growth factor receptor 2-negative (ER+/PR+/HER2−) breast cancer and nodal status of N0, N1mi with 1 (Nmic1) or more (Nmic > 1) involved nodes, and N1 with 1 involved node (N1.1), from 2010 to 2016. Patients with different nodal statuses were compared regarding treatment characteristics, survival, and benefit from chemotherapy by their 21-gene recurrence score (RS).

Results

Of the 23,072 N1mi patients, 88.3% were Nmic1 and 11.7% were Nmic > 1. Nmic > 1 patients were younger, had larger and higher-grade tumors, with more lymphovascular invasion, and were more commonly treated by axillary dissection, radiation, and chemotherapy than Nmic1 patients. In that, they were comparable with N1.1 patients. Five-year survival of Nmic > 1 patients (88.1%) was worse than Nmic1 patients (90.1%; p = 0.02), but similar to N1.1 patients (87.9%). Nmic1, Nmic > 1, and N1.1 patients with RS 11–25 exhibited a < 2% absolute survival benefit associated with chemotherapy. With RS > 25, Nmic > 1 patients showed a 3.5% benefit, similar to Nmic1 (4.8%) and lower than N1.1 (10.9%) patients.

Conclusions

Nmic > 1 breast cancer patients have worse prognoses than Nmic1 patients, similar to N1.1 patients. Our data suggest those patients with RS 11–25 have minimal benefit from chemotherapy. These findings should be taken into account when discussing prognosis and considering chemotherapy in patients with lymphatic micrometastases.

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References

  1. Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Murphy GP. Management and survival of female breast cancer: results of a national survey by the American College of Surgeons. Cancer. 1980;45(12):2917–24. https://doi.org/10.1002/1097-0142(19800615)45:12%3c2917::aid-cncr2820451203%3e3.0.co;2-m.

    Article  CAS  PubMed  Google Scholar 

  2. Carter CL, Allen C, Henson DE. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989;63(1):181–7. https://doi.org/10.1002/1097-0142(19890101)63:1%3c181::aid-cncr2820630129%3e3.0.co;2-h.

    Article  CAS  PubMed  Google Scholar 

  3. Huvos AG, Hutter RV, Berg JW. Significance of axillary macrometastases and micrometastases in mammary cancer. Ann Surg. 1971;173(1):44–6. https://doi.org/10.1097/00000658-197101000-00006.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Beahrs OH, Myers MH, American Joint Committee on Cancer (eds). Manual for Staging of Cancer. 2nd ed. Philadelphia: Lippincott; 1983.

  5. Greene FL, American Joint Committee on Cancer, American Cancer Society (eds). AJCC cancer staging manual. 6th ed. New York: Springer; 2002.

  6. Singletary SE, Allred C, Ashley P, et al. Revision of the American Joint Committee on cancer staging system for breast cancer. J Clin Oncol. 2002;20(17):3628–36. https://doi.org/10.1200/JCO.2002.02.026.

    Article  PubMed  Google Scholar 

  7. de Boer M, van Deurzen CHM, van Dijck JAAM, et al. Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J Med. 2009;361(7):653–63. https://doi.org/10.1056/NEJMoa0904832.

    Article  PubMed  Google Scholar 

  8. Clare SE, Sener SF, Wilkens W, Goldschmidt R, Merkel D, Winchester DJ. Prognostic significance of occult lymph node metastases in node-negative breast cancer. Ann Surg Oncol. 1997;4(6):447–51. https://doi.org/10.1007/BF02303667.

    Article  CAS  PubMed  Google Scholar 

  9. de Mascarel I, Bonichon F, Coindre JM, Trojani M. Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. Br J Cancer. 1992;66(3):523–7. https://doi.org/10.1038/bjc.1992.306.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dowlatshahi K, Fan M, Snider HC, Habib FA. Lymph node micrometastases from breast carcinoma: reviewing the dilemma. Cancer. 1997;80(7):1188–97. https://doi.org/10.1002/(sici)1097-0142(19971001)80:7%3c1188::aid-cncr2%3e3.0.co;2-h.

    Article  CAS  PubMed  Google Scholar 

  11. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. International (Ludwig) Breast Cancer Study Group. Lancet. 1990;335(8705):1565–8.

  12. Clayton F, Hopkins CL. Pathologic correlates of prognosis in lymph node-positive breast carcinomas. Cancer. 1993;71(5):1780–90. https://doi.org/10.1002/1097-0142(19930301)71:5%3c1780::aid-cncr2820710512%3e3.0.co;2-2.

    Article  CAS  PubMed  Google Scholar 

  13. Antolini L, Biganzoli E, Querzoli P, Piantelli M, Alberti S. Lymph node micrometastases do influence breast cancer outcome. J Clin Oncol. 2015;33(33):3977–8. https://doi.org/10.1200/JCO.2015.63.0962.

    Article  PubMed  Google Scholar 

  14. Park D, Kåresen R, Naume B, Synnestvedt M, Beraki E, Sauer T. The prognostic impact of occult nodal metastasis in early breast carcinoma. Breast Cancer Res Treat. 2009;118(1):57–66. https://doi.org/10.1007/s10549-009-0340-2.

    Article  PubMed  Google Scholar 

  15. Jafferbhoy S, McWilliams B. Clinical significance and management of sentinel node micrometastasis in invasive breast cancer. Clin Breast Cancer. 2012;12(5):308–12. https://doi.org/10.1016/j.clbc.2012.07.012.

    Article  PubMed  Google Scholar 

  16. Kuijt GP, Voogd AC, van de Poll-Franse LV, Scheijmans LJEE, van Beek MWPM, Roumen RMH. The prognostic significance of axillary lymph-node micrometastases in breast cancer patients. Eur J Surg Oncol. 2005;31(5):500–5. https://doi.org/10.1016/j.ejso.2005.01.001.

    Article  CAS  PubMed  Google Scholar 

  17. Henry NL, Somerfield MR, Abramson VG, et al. Role of patient and disease factors in adjuvant systemic therapy decision making for early-stage, operable breast cancer: update of the ASCO Endorsement of the Cancer Care Ontario Guideline. J Clin Oncol. 2019;37(22):1965–77. https://doi.org/10.1200/JCO.19.00948.

    Article  PubMed  Google Scholar 

  18. Giuliano AE, Edge SB, Hortobagyi GN. Eighth edition of the AJCC Cancer Staging Manual: breast cancer. Ann Surg Oncol. 2018;25(7):1783–5. https://doi.org/10.1245/s10434-018-6486-6.

    Article  PubMed  Google Scholar 

  19. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45(6):613–9. https://doi.org/10.1016/0895-4356(92)90133-8.

    Article  CAS  PubMed  Google Scholar 

  20. Weiser R, Haque W, Polychronopoulou E, et al. The 21-gene recurrence score in node-positive, hormone receptor-positive, HER2-negative breast cancer: a cautionary tale from an NCDB analysis. Breast Cancer Res Treat. 2021;185(3):667–76. https://doi.org/10.1007/s10549-020-05971-1.

    Article  CAS  PubMed  Google Scholar 

  21. Sparano JA, Gray RJ, Makower DF, et al. Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2015;373(21):2005–14. https://doi.org/10.1056/NEJMoa1510764.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. van der Heiden-van der Loo M, Bezemer PD, Hennipman A, et al. Introduction of sentinel node biopsy and stage migration of breast cancer. Eur J Surg Oncol. 2006;32(7):710-714. doi:https://doi.org/10.1016/j.ejso.2006.04.001

  23. Bolster MJ, Bult P, Schapers RFM, et al. Differences in sentinel lymph node pathology protocols lead to differences in surgical strategy in breast cancer patients. Ann Surg Oncol. 2006;13(11):1466–73. https://doi.org/10.1245/s10434-006-9084-y.

    Article  PubMed  Google Scholar 

  24. Galimberti V, Cole BF, Zurrida S, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23–01): a phase 3 randomised controlled trial. Lancet Oncol. 2013;14(4):297–305. https://doi.org/10.1016/S1470-2045(13)70035-4.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Galimberti V, Cole BF, Viale G, et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23–01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol. 2018;19(10):1385–93. https://doi.org/10.1016/S1470-2045(18)30380-2.

    Article  PubMed  Google Scholar 

  26. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017;318(10):918. https://doi.org/10.1001/jama.2017.11470.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981–22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;15(12):1303–10. https://doi.org/10.1016/S1470-2045(14)70460-7.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Maibenco DC, Dombi GW, Kau TY, Severson RK. Significance of micrometastases on the survival of women with T1 breast cancer. Cancer. 2006;107(6):1234–9. https://doi.org/10.1002/cncr.22112.

    Article  PubMed  Google Scholar 

  29. Grabau D, Jensen MB, Rank F, Blichert-Toft M. Axillary lymph node micrometastases in invasive breast cancer: national figures on incidence and overall survival. APMIS. 2007;115(7):828–37. https://doi.org/10.1111/j.1600-0463.2007.apm_442.x.

    Article  CAS  PubMed  Google Scholar 

  30. Cortesi L, Proietto M, Cirilli C, Tazzioli G, Andreotti A, Federico M. Prognosis and treatment of micrometastatic breast cancer sentinel lymph node: a population-based study. J Surg Oncol. 2012;106(4):399–405. https://doi.org/10.1002/jso.23111.

    Article  PubMed  Google Scholar 

  31. Hetterich M, Gerken M, Ortmann O, et al. Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases. Breast Cancer Res Treat. 2021;187(3):715–27. https://doi.org/10.1007/s10549-021-06162-2.

    Article  CAS  PubMed  Google Scholar 

  32. Kalinsky K, Barlow W, Meric-Bernstam F, Garlow J, Albain K. Oral presentation [GS3-00], SWOG S1007: adjuvant trial randomized ER+ patients who had a Recurrence Score <25 and 1-3 positive nodes to endocrine therapy (ET) versus ET + chemotherapy. San Antonio Breast Cancer Symposium; 8–11 Dec 2020.

  33. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111–21. https://doi.org/10.1056/NEJMoa1804710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer. Version 3.2020. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

  35. Wu SP, Tam M, Shaikh F, et al. Post-mastectomy radiation therapy in breast cancer patients with nodal micrometastases. Ann Surg Oncol. 2018;25(9):2620–31. https://doi.org/10.1245/s10434-018-6632-1.

    Article  PubMed  Google Scholar 

  36. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. The Lancet. 2014;383(9935):2127-2135. https://doi.org/10.1016/S0140-6736(14)60488-8

  37. Kayali M, Abi Jaoude J, Tfayli A, El Saghir N, Poortmans P, Zeidan YH. Post-mastectomy radiation therapy in breast cancer patients with 1–3 positive lymph nodes: no one size fits all. Crit Rev Oncol Hematol. 2020;147:102880. https://doi.org/10.1016/j.critrevonc.2020.102880.

    Article  PubMed  Google Scholar 

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Funding

Funding was provided by the Courtney M. Townsend, Jr. M.D. Distinguished Chair in General Surgery, University of Texas Medical Branch, Galveston, TX.

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Authors and Affiliations

  1. Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA

    Roi Weiser MD & V. Suzanne Klimberg MD, PhD, MSHCT, FACS

  2. Department of Preventive Medicine and Population Health, Office of Biostatistics, University of Texas Medical Branch, Galveston, TX, USA

    Efstathia Polychronopoulou MSc & Yong-fang Kuo PhD

  3. Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA

    Waqar Haque MD, MS

  4. Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, USA

    Sandra S. Hatch MD

  5. Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA

    Jing He MD, MS & Suimin Qiu MD, PhD

  6. Division of Hematology/Oncology, University of Texas Medical Branch, Galveston, TX, USA

    Avi Markowitz MD

  7. Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

    William J. Gradishar MD

  8. MD Anderson Cancer Center, Houston, TX, USA

    V. Suzanne Klimberg MD, PhD, MSHCT, FACS

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Correspondence to Roi Weiser MD or V. Suzanne Klimberg MD, PhD, MSHCT, FACS.

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Roi Weiser, Efstathia Polychronopoulou, Waqar Haque, Sandra S. Hatch, Jing He, Suimin Qiu, Avi Markowitz, William J. Gradishar, Yong-fang Kuo, and V. Suzanne Klimberg have no disclosures to declare.

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Weiser, R., Polychronopoulou, E., Haque, W. et al. Prognosis and Chemotherapy Use in Breast Cancer Patients with Multiple Lymphatic Micrometastases: An NCDB Analysis. Ann Surg Oncol 28, 8717–8727 (2021). https://doi.org/10.1245/s10434-021-10374-7

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