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Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases

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Abstract

Background

The axillary lymph node status is one of the most important prognostic factors in patients with early breast cancer. However, the impact of axillary lymph node micrometastases on survival remains unclear. There are no consistent recommendations for adjuvant chemotherapy (CHT). In this context, we aimed to investigate the impact of micrometastases on the clinical outcome of breast cancer patients according to the adjuvant CHT performed.

Patients and methods

We conducted a retrospective population-based registry study of 26,465 patients aged between 24 and 97 years with primary breast cancer diagnosed between 2003 and 2017. Of these patients, 8856 with early breast cancer were eligible for analysis: 8316 (93.9%) were node negative and 540 (6.1%) had lymph node micrometastases.

Results

The median follow-up was 7.2 years, with a confidence interval (CI) of 7.1–7.3 years. Patients with lymph node micrometastases (pN1mi) without adjuvant CHT have reduced 10-year overall survival (OS) and recurrence-free survival (RFS) compared to patients who had axillary lymph node micrometastases and received an adjuvant CHT. However, this effect disappeared after adjustment for age, tumor size and tumor grading. Furthermore, in the group of patients with lymph node micrometastases, the administration of adjuvant CHT did not improve OS or RFS, compared to patients with lymph node micrometastases without adjuvant CHT: hazard ratio for treated patients was 1.51 (95% CI 0.80–2.85, p = 0.208) for OS and 1.12 (95% CI 0.63–1.97, p = 0.705) for RFS.

Conclusion

Patients with axillary lymph node micrometastases showed a comparable outcome to node negative patients and their outcome was not significantly improved with CHT. Thus, axillary lymph node micrometastases should not be considered in the treatment decision.

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Data availability

The data are available and will be sent on request.

References

  1. Fisher B, Bauer M, Wickerham DL et al (1983) Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update Cancer 52:1551–1557. https://doi.org/10.1002/1097-0142(19831101)52:9%3c1551::AID-CNCR2820520902%3e3.0.CO;2-3

    Article  CAS  PubMed  Google Scholar 

  2. Hatoum HA, Jamali FR, El-Saghir NS et al (2010) Ratio between positive lymph nodes and total excised axillary lymph nodes as an independent prognostic factor for overall survival in patients with nonmetastatic lymph node-positive breast cancer. Indian J Surg Oncol 1:68–75. https://doi.org/10.1007/s13193-010-0018-6

    Article  PubMed  PubMed Central  Google Scholar 

  3. Viale G, Maiorano E, Mazzarol G et al (2001) Histologic detection and clinical implications of micrometastases in axillary sentinel lymph nodes for patients with breast carcinoma. Cancer 92:1378–1384. https://doi.org/10.1002/1097-0142(20010915)92:6%3c1378::AID-CNCR1460%3e3.0.CO;2-Y

    Article  CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  5. Veronesi U, Paganelli G, Viale G et al (2003) A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med 349:546–553. https://doi.org/10.1056/NEJMoa012782

    Article  PubMed  Google Scholar 

  6. Krag DN, Anderson SJ, Julian TB et al (2010) Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol 11:927–933. https://doi.org/10.1016/S1470-2045(10)70207-2

    Article  PubMed  PubMed Central  Google Scholar 

  7. Maaskant AJG, Van De Poll-Franse LV, Voogd AC et al (2009) Stage migration due to introduction of the sentinel node procedure: a population-based study. Breast Cancer Res Treat 113:173–179. https://doi.org/10.1007/s10549-008-9913-8

    Article  CAS  PubMed  Google Scholar 

  8. Wittekind C (2016) TNM classification of malignant tumours, 8th edn. Wiley, New York, pp 151–158

    Google Scholar 

  9. Tjan-Heijnen VCG, Bult P, De Widt-Levert LM et al (2001) Micro-metastases in axillary lymph nodes: an increasing classification and treatment dilemma in breast cancer due to the introduction of the sentinel lymph node procedure. Breast Cancer Res Treat 70:81–88. https://doi.org/10.1023/A:1012938825396

    Article  CAS  PubMed  Google Scholar 

  10. Cserni G (1999) Metastases in axillary sentinel lymph nodes in breast cancer as detected by intensive histopathological work up. J Clin Pathol 52:922–924. https://doi.org/10.1136/jcp.52.12.922

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Giuliano AE, Dale PS, Turner RR et al (1995) Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 222:394–401. https://doi.org/10.1097/00000658-199509000-00016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Weaver DL, Krag DN, Ashikaga T et al (2000) Pathologic analysis of sentinel and nonsentinel lymph nodes in breast carcinoma: a multicenter study. Cancer 88:1099–1107. https://doi.org/10.1002/(SICI)1097-0142(20000301)88:5%3c1099::AID-CNCR22%3e3.0.CO;2-7

    Article  CAS  PubMed  Google Scholar 

  13. Patani N, Mokbel K (2009) The clinical significance of sentinel lymph node micrometastasis in breast cancer. Breast Cancer Res Treat 114:393–402. https://doi.org/10.1007/s10549-008-0021-6

    Article  PubMed  Google Scholar 

  14. de Boer M, van Deurzen CH, van Dijck JA et al (2009) Micrometastases or isolated tumor cells and the outcome of breast cancer. N Engl J M 361:653–663. https://doi.org/10.1056/nejmoa0904832

    Article  Google Scholar 

  15. Hansen NM, Grube B, Ye X et al (2009) Impact of micrometastases in the sentinel node of patients with invasive breast cancer. J Clin Oncol 27:4679–4684. https://doi.org/10.1200/JCO.2008.19.0686

    Article  PubMed  Google Scholar 

  16. Grabau D, Jensen MB, Rank F, Blichert-Toft M (2007) Axillary lymph node micrometastases in invasive breast cancer: national figures on incidence and overall survival. APMIS 115:828–837. https://doi.org/10.1111/j.1600-0463.2007.apm_442.x

    Article  CAS  PubMed  Google Scholar 

  17. Gobardhan PD, Elias SG, Madsen EVE et al (2009) Prognostic value of micrometastases in sentinel lymph nodes of patients with breast carcinoma: a cohort study. Ann Oncol 20:41–48. https://doi.org/10.1093/annonc/mdn535

    Article  CAS  PubMed  Google Scholar 

  18. Chen SL, Hoehne FM, Giuliano AE (2007) The prognostic significance of micrometastases in breast cancer: a SEER population-based analysis. Ann Surg Oncol 14:3378–3384. https://doi.org/10.1245/s10434-007-9513-6

    Article  PubMed  Google Scholar 

  19. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF) (2020) S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Mammakarzinoms, Version 4.3, AWMF, Registernummer: 032-045OL. pp 101, 143–168.

  20. Langer I, Guller U, Viehl CT et al (2009) Axillary lymph node dissection for sentinel lymph node micrometastases may be safely omitted in early-stage breast cancer patients: long-term outcomes of a prospective study. Ann Surg Oncol 16:3366–3374. https://doi.org/10.1245/s10434-009-0660-9

    Article  PubMed  Google Scholar 

  21. Maaskant-Braat AJ, Voogd AC, van de Poll-Franse LV et al (2012) Axillary and systemic treatment of patients with breast cancer and micrometastatic disease or isolated tumor cells in the sentinel lymph node. Breast 21:524–528. https://doi.org/10.1016/j.breast.2012.03.008

    Article  PubMed  Google Scholar 

  22. Taubenhansl C, Ortmann O, Gerken M et al (2019) Guideline-concordant chemotherapy in patients with hormone receptor-positive and node-positive, early breast cancer leads to better overall and metastases-free survival with limited benefit in elderly patients. Arch Gynecol Obstet. https://doi.org/10.1007/s00404-019-05387-3

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ignatov T, Eggemann H, Costa SD et al (2018) Endometrial cancer subtypes are associated with different patterns of recurrence. J Cancer Res Clin Oncol 144:2011–2017. https://doi.org/10.1007/s00432-018-2711-8

    Article  CAS  PubMed  Google Scholar 

  24. Ignatov A, Lebius C, Ignatov T et al (2019) Lymph node micrometastases and outcome of endometrial cancer. Gynecol Oncol 154:475–479. https://doi.org/10.1016/j.ygyno.2019.07.018

    Article  PubMed  Google Scholar 

  25. von Elm E, Altman DG, Egger M et al (2008) The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61:344–349. https://doi.org/10.1016/j.jclinepi.2007.11.008

    Article  Google Scholar 

  26. Redig AJ, Mcallister SS (2013) Breast cancer as a systemic disease: a view of metastasis. J Intern Med 274:113–126. https://doi.org/10.1111/joim.12084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gill G (2009) Sentinel-lymph-node-based management or routine axillary clearance? One-year outcomes of sentinel node biopsy versus axillary clearance (SNAC): a randomized controlled surgical trial. Ann Surg Oncol 16:266–275. https://doi.org/10.1245/s10434-008-0229-z

    Article  PubMed  Google Scholar 

  28. Goyal A, Newcombe RG, Chhabra A, Mansel RE (2006) Factors affecting failed localisation and false-negative rates of sentinel node biopsy in breast cancer: results of the ALMANAC validation phase. Breast Cancer Res Treat 99:203–208. https://doi.org/10.1007/s10549-006-9192-1

    Article  PubMed  Google Scholar 

  29. Krag DN, Anderson SJ, Julian TB et al (2007) Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial. Lancet Oncol 8:881–888. https://doi.org/10.1016/S1470-2045(07)70278-4

    Article  CAS  PubMed  Google Scholar 

  30. Veronesi U, Paganelli G, Viale G et al (2006) Sentinel-lymph-node biopsy as a staging procedure in breast cancer: update of a randomised controlled study. Lancet Oncol 7:983–990. https://doi.org/10.1016/S1470-2045(06)70947-0

    Article  PubMed  Google Scholar 

  31. Rivera M, Merlin S, Hoda RS et al (2004) Minimal involvement of sentinel lymph node in breast carcinoma: prevailing concepts and challenging problems. Int J Surg Pathol 12:301–306. https://doi.org/10.1177/106689690401200402

    Article  PubMed  Google Scholar 

  32. Salhab M, Patani N, Mokbel K (2011) Sentinel lymph node micrometastasis in human breast cancer: an update. Surg Oncol 20:e195–e206. https://doi.org/10.1016/j.suronc.2011.06.006

    Article  PubMed  Google Scholar 

  33. Chagpar A, Middleton LP, Sahin AA et al (2005) Clinical outcome of patients with lymph node-negative breast carcinoma who have sentinel lymph node micrometastases detected by immunohistochemistry. Cancer 103:1581–1586. https://doi.org/10.1002/cncr.20934

    Article  PubMed  Google Scholar 

  34. Kahn HJ, Hanna WM, Chapman JAW et al (2006) Biological significance of occult micrometastases in histologically negative axillary lymph nodes in breast cancer patients using the recent American Joint Committee on Cancer breast cancer staging system. Breast J 12:294–301. https://doi.org/10.1111/j.1075-122X.2006.00267.x

    Article  PubMed  Google Scholar 

  35. Wong SL, Chao C, Edwards MJ et al (2001) The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer. Am J Surg 182:330–334. https://doi.org/10.1016/S0002-9610(01)00722-X

    Article  CAS  PubMed  Google Scholar 

  36. Maaskant-Braat AJ, Van De Poll-Franse LV, Voogd AC et al (2011) Sentinel node micrometastases in breast cancer do not affect prognosis: a population-based study. Breast Cancer Res Treat 127:195–203. https://doi.org/10.1007/s10549-010-1086-6

    Article  PubMed  Google Scholar 

  37. Cote R, Giuliano AE, Hawes D et al (2010) ACOSOG Z0010: a multicenter prognostic study of sentinel node (SN) and bone marrow (BM) micrometastases in women with clinical T1/T2 N0 M0 breast cancer. J Clin Oncol 28:CRA504. https://doi.org/10.1200/jco.2010.28.18_suppl.cra504

    Article  Google Scholar 

  38. Langer I, Marti WR, Guller U et al (2005) Axillary recurrence rate in breast cancer patients with negative sentinel lymph node (SLN) or SLN micrometastases: prospective analysis of 150 patients after SLN biopsy. Ann Surg 241:152–158. https://doi.org/10.1097/01.sla.0000149305.23322.3c

    Article  PubMed  PubMed Central  Google Scholar 

  39. Colpaert C, Vermeulen P, Jeuris W et al (2001) Early distant relapse in “node-negative” breast cancer patients is not predicted by occult axillary lymph node metastases, but by the features of the primary tumour. J Pathol 193:442–449. https://doi.org/10.1002/path.829

    Article  CAS  PubMed  Google Scholar 

  40. Millis RR, Springall R, Lee AHS et al (2002) Occult axillary lymph node metastases are of no prognostic significance in breast cancer. Br J Cancer 86:396–401. https://doi.org/10.1038/sj.bjc.6600070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. De Mascarel I, Bonichon F, Coindre JM, Trojani M (1992) Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. Br J Cancer 66:523–527. https://doi.org/10.1038/bjc.1992.306

    Article  PubMed  PubMed Central  Google Scholar 

  42. Cox CE, Kiluk JV, Riker AI et al (2008) Significance of sentinel lymph node micrometastases in human breast cancer. J Am Coll Surg 206:261–268. https://doi.org/10.1016/j.jamcollsurg.2007.08.024

    Article  PubMed  Google Scholar 

  43. Reed J, Rosman M, Verbanac KM et al (2009) Prognostic implications of isolated tumor cells and micrometastases in sentinel nodes of patients with invasive breast cancer: 10-year analysis of patients enrolled in the prospective east Carolina University/Anne Arundel Medical Center Sentinel Node Mult. J Am Coll Surg 208:333–340. https://doi.org/10.1016/j.jamcollsurg.2008.10.036

    Article  PubMed  Google Scholar 

  44. Montagna E, Viale G, Rotmensz N et al (2009) Minimal axillary lymph node involvement in breast cancer has different prognostic implications according to the staging procedure. Breast Cancer Res Treat 118:385–394. https://doi.org/10.1007/s10549-009-0446-6

    Article  CAS  PubMed  Google Scholar 

  45. Bae HW, Yoon KH, Kim JH et al (2018) Impact of micrometastatic axillary nodes on survival of breast cancer patients with tumors ≤2 cm. World J Surg 42:3969–3978. https://doi.org/10.1007/s00268-018-4725-4

    Article  PubMed  Google Scholar 

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Funding

This study was not funded.

Author information

Author notes

  1. Holm Eggemann and Atanas Ignatov have been equally contributed as senior author.

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University Medical Center Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany

    Madeleine Hetterich, Olaf Ortmann, Elisabeth C. Inwald & Atanas Ignatov

  2. Tumor Center Regensburg, Institute for Quality Assurance and Health Services Research, University of Regensburg, Regensburg, Germany

    Michael Gerken & Monika Klinkhammer-Schalke

  3. Department of Gynecology and Obstetrics, Clinic Magdeburg, Magdeburg, Germany

    Holm Eggemann

  4. Department of Gynecology and Obstetrics, Otto-Von-Guericke University, Magdeburg, Germany

    Atanas Ignatov

Authors
  1. Madeleine Hetterich
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  2. Michael Gerken
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  3. Olaf Ortmann
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  4. Elisabeth C. Inwald
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Correspondence to Atanas Ignatov.

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The authors have no conflict of interest.

Ethical approval

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 article does not contain any studies with animals performed by any of the authors.

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Written informed consent was obtained from all patients before treatment. The local Ethics Committee of the Otto-von-Guericke University, Magdeburg, Germany ruled that no formal ethics approval was required for this study.

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Hetterich, M., Gerken, M., Ortmann, O. et al. Adjuvant chemotherapy for breast cancer patients with axillary lymph node micrometastases. Breast Cancer Res Treat 187, 715–727 (2021). https://doi.org/10.1007/s10549-021-06162-2

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  • DOI: https://doi.org/10.1007/s10549-021-06162-2

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