Contralateral Axillary Lymph Node Metastases from Breast Carcinoma: Is it Time to Review TNM Cancer Staging?

Abstract

Background

Contralateral axillary lymph node metastasis (CAM) is an infrequent clinical condition currently considered an M1, stage IV, disease. Due to the absence of shared data on CAM significance and on its therapeutic approach, be it curative or simply palliative, its management is still uncertain and undoubtedly represents a clinical challenge.

Patients and Methods

Patients with pathologically confirmed metachronous CAM were retrospectively evaluated. All patients had been managed at the European Institute of Oncology, Milan, Italy, from 1997. Patients with distant metastases at the time of CAM were excluded. Possible treatments included surgery, systemic therapy and RT (radiotherapy). Outcomes were evaluated as rates of disease-free survival (DFS) and of overall survival (OS).

Results

Forty-seven patients with CAM were included in the study. Metachronous CAM occurred 73 months (range 5–500 months) after diagnosis of the primary tumor. The median follow-up time was 5.4 years (interquartile range 2.9–7.0 years). The estimated OS was 72% at 5 years (95% CI 54–83), and 61% at 8 years (95% CI 43–75). The estimated DFS was 61% at 5 years (95% CI 44–74), and 42% at 8 years (95% CI 25–59).

Conclusion

These findings, together with those from previous studies, show that CAM outcome, particularly if measured as OS, appear better than at other sites of distant dissemination, when CAM is subjected to surgical and systemic treatments with a curative intent. Therefore, a new clinical scenario is suggested where, in the TNM system, CAM is no longer classified as a stage IV, but as an N3 disease.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

References

  1. 1.

    Gingerich J, Kapenhas E, Morgani J, Heimann A. Contralateral axillary lymph node metastasis in second primary breast cancer: case report and review of the literature. Int J Surg Case Rep. 2017;40:47–9.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Vlastos G, Jean ME, Mirza, AN, et al. Feasibility of breast preservation in the treatment of occult primary carcinoma presenting with axillary metastases. Ann Surg Oncol. 2001;8:425.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Jaffer S, Goldfarb AB, Gold JE, et al. Contralateral axillary lymph node metastasis as the first evidence of locally recurrent breast carcinoma. Cancer. 1995;75:2875–8.

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Moossdorff M, Vugts G, Maaskant-Braat AJG, et al. Contralateral lymph node recurrence in breast cancer: regional event rather than distant metastatic disease. A systematic review of the literature. Eur J Surg Oncol. 2015;41(9):1128–36.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Boughey JC, Ross MI, Babiera GV, et al. Sentinel lymph node surgery in locally recurrent breast cancer. Clin Breast Cancer. 2006;7:248–53.

    PubMed  Article  Google Scholar 

  6. 6.

    Maaskant-Braat, AJG, Voogd, AC, Roumen RMH, et al. Repeat sentinel node biopsy in patients with locally recurrent breast cancer: a systematic review and meta-analysis of the literature. Breast Cancer Res Treat. 2013;138:13.

    PubMed  Article  Google Scholar 

  7. 7.

    Port ER, Garcia-Etienne CA, Park J, et al. Reoperative sentinel lymph node biopsy: a new frontier in the management of ipsilateral breast tumor recurrence. Ann Surg Oncol. 2007;14:2209.

    PubMed  Article  Google Scholar 

  8. 8.

    Taback, B, Nguyen P, Hansen N, et al. Sentinel lymph node biopsy for local recurrence of breast cancer after breast-conserving therapy. Ann Surg Oncol. 2006;13:1099.

    PubMed  Article  Google Scholar 

  9. 9.

    Wellner R, Dave J, Kim U, Menes TS. Altered lymphatic drainage after breast-conserving surgery and axillary node dissection: local recurrence with contralateral intramammary nodal metastases. Clin Breast Cancer. 2007;7:486–8.

    PubMed  Article  Google Scholar 

  10. 10.

    Estourgie SH, Valdés Olmos RA, Nieweg OE, et al. Excision biopsy of breast lesions changes the pattern of lymphatic drainage. Br J Surg. 2007;94:1088–91.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Barranger E, Montravers F, Kerrou K, et al. Contralateral axillary sentinel lymph node drainage in breast cancer: a case report. J Surg Oncol. 2004;86:167–9.

    PubMed  Article  Google Scholar 

  12. 12.

    Lizarraga IM, Sugg SL, Weigel RJ, Scott-Conner CE. Review of risk factors for the development of contralateral breast cancer. Am J Surg. 2013;206:704–8.

    PubMed  Article  Google Scholar 

  13. 13.

    Trifirò G, Ravasi L, Paganelli G. Contralateral or bilateral lymph drainage revealed by breast lymphoscintigraphy. Eur J Nucl Med Mol Imaging. 2008;35:225.

    PubMed  Article  Google Scholar 

  14. 14.

    Edge SB, Byrd DR, Compton CC, et al. AJCC cancer staging manual. 7th ed. New York: Springer; 2010.

    Google Scholar 

  15. 15.

    Amin MB, Greene FL, Edge SB, et al. The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin. 2017;67:93–9.

    PubMed  Article  Google Scholar 

  16. 16.

    Perre CI, Hoefnagel CA, Kroon BB, et al. Altered lymphatic drainage after lymphadenectomy or radiotherapy of the axilla in patients with breast cancer. Br J Surg. 1996;83:1258–1258.

    CAS  PubMed  Article  Google Scholar 

  17. 17.

    Lim I, Shim J, Goyenechea M, et al. Drainage across midline to sentinel nodes in the contralateral axilla in breast cancer. Clin Nucl Med. 2004;29(6):346–7.

    PubMed  Article  Google Scholar 

  18. 18.

    Kim SJ, Moon WK, Cho N, Chang JM. The detection of recurrent breast cancer in patients with a history of breast cancer surgery: comparison of clinical breast examination, mammography and ultrasonography. Acta Radiol. 2011;52:15–20.

    PubMed  Article  Google Scholar 

  19. 19.

    Huston TL, Pressman PI, Moore A, et al. The presentation of contralateral axillary lymph node metastases from breast carcinoma: a clinical management dilemma. Breast J. 2007;13:158–64.

    PubMed  Article  Google Scholar 

  20. 20.

    Morcos B, Jaradat I, El-Ghanem M. Characteristics of and therapeutic options for contralateral axillary lymph node metastasis in breast cancer. Eur J Surg Oncol. 2011;37:418–21.

    CAS  PubMed  Article  Google Scholar 

  21. 21.

    Daoud M, Meziou M, Kharrat D, et al. Contralateral axillary lymph node metastasis of cancer of the breast. Bull Cancer. 1998;85:713–5.

    CAS  PubMed  Google Scholar 

  22. 22.

    Chkheidze R, Sanders MAG, Haley B, et al. Isolated contralateral axillary lymph node involvement in breast cancer represents a locally advanced disease not distant metastases. Clin Breast Cancer. 2017;18(4):298–304.

    PubMed  Article  Google Scholar 

  23. 23.

    Wang W, Yuan P, Wang J, et al. Management of contralateral axillary lymph node metastasis from breast cancer: a clinical dilemma. Tumori. 2014;100(6):600–4.

    PubMed  Article  Google Scholar 

  24. 24.

    Brito RA, Valero V, Buzdar AU, et al. Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: the University of Texas M.D. Anderson Cancer Center experience. J Clin Oncol. 2011;19:628–33.

    Article  Google Scholar 

  25. 25.

    Kim JY, Lee H, Kim TS, Kang HS, Kim SK. Unusual contralateral axillary lymph node metastasis in a second primary breast cancer detected by FDG PET/CT and lymphoscintigraphy. Nucl Med Mol Imaging. 2017;51(4):350–3.

    PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Strazzanti A, Gangi S, Trovato C, et al. Contralateral lymph node metastasis in a woman with new primary breast cancer: systemic disease or locoregional diffusion? Int J Surg Case Rep. 2018;53:400–2.

    PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Dayyat A, Sbaity E, Mula-Hussain L, et al. Treatment of contralateral axillary metastases: palliative vs curative dilemma. Ann Hematol Oncol. 2014;1(2):1006.

    Google Scholar 

  28. 28.

    Schlechter BL, Yang Q, Larson PS, et al. Quantitative DNA fingerprinting may distinguish new primary breast cancer from disease recurrence. J Clin Oncol. 2004; 22:1830–8.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Agarwal A, Heron DE, Sumkin J, Falk J. Contralateral uptake and metastases in sentinel lymph node mapping for recurrent breast cancer. J Surg Oncol. 2005;92:4–8.

    PubMed  Article  Google Scholar 

  30. 30.

    Roumen RM, Kuijt GP, Liem IH. Lymphatic mapping and sentinel node harvesting in patients with recurrent breast cancer. Eur J Surg Oncol. 2006;32:1076–81.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Koizumi M, Koyama M, Tada K, et al. The feasibility of sentinel node biopsy in the previously treated breast. Eur J Surg Oncol. 2008; 34:365–8.

    CAS  PubMed  Article  Google Scholar 

  32. 32.

    Kroon BB, Hoefnagel CA, Valdes Olmos RA, Nieweg OE. Regional lymph nodes at a distance. Ned Tijdschr Geneeskd. 2008;152:1997–2000.

    CAS  PubMed  Google Scholar 

  33. 33.

    Lanitis S, Behranwala KA, Al-Mufti R, Hadjiminas D. Axillary metastatic disease as presentation of occult or contralateral breast cancer. Breast. 2009;18:225–7.

    CAS  PubMed  Article  Google Scholar 

  34. 34.

    Tasevski R, Gogos AJ, Mann GB. Reoperative sentinel lymph node biopsy in ipsilateral breast cancer relapse. Breast. 2009;18:322–6.

    CAS  PubMed  Article  Google Scholar 

  35. 35.

    van der Ploeg IM, Oldenburg HS, Rutgers EJ, et al. Lymphatic drainage patterns from the treated breast. Ann Surg Oncol. 2010;17:1069–75.

    PubMed  Article  Google Scholar 

  36. 36.

    Kinoshita S, Hirano A, Kobayashi S, et al. Metachronous secondary primary occult breast cancer initially presenting with metastases to the contralateral axillary lymph nodes: report of a case. Breast Cancer. 2010;17:71–4.

    PubMed  Article  Google Scholar 

  37. 37.

    Herold CI, Gaughan EM, Lamb CC, Tung NM. Second primary ipsilateral breast cancer with contralateral axillary involvement: a case report and literature review. Clin Breast Cancer. 2011;11:406–8.

    PubMed  Article  Google Scholar 

  38. 38.

    Sabate M, Roca I, Cordoba O, et al. Contralateral axillary drainage in breast tumor recurrence. Rev Esp Med Nucl. 2011;30:327–8.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Kiluk JV, Prowler V, Lee MC, et al. Cox contralateral axillary nodal involvement from invasive breast cancer. Breast. 2004;23:291–4.

    Article  Google Scholar 

  40. 40.

    Nishimura S, Koizumi M, Kawakami J, Koyama M. Contralateral axillary node metastasis from recurrence after conservative breast cancer surgery. Clin Nucl Med. 2014;39:181–3.

    PubMed  Article  Google Scholar 

  41. 41.

    Pasta V, Urciuoli P, Orazi V, Sottile D, et al. Contralateral axillary metastases from breast cancer. Personal experience and review of literature. Ann Ital Chir. 2014;85:260–4.

    PubMed  Google Scholar 

  42. 42.

    Tokmak H, Kaban K, Muslumanoglu M, et al. Management of sentinel node re-mapping in patients who have second or recurrent breast cancer and had previous axillary procedures. World J Surg Oncol. 2014;12:205.

    PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Clemons M, Danson S, Hamilton T et al. Locoregionally recurrent breast cancer: incidence, risk factors and survival. Cancer Treat Rev. 2001; 27(2): 67–82.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Shenouda MN, Sadek BT, Goldberg SI, et al. Clinical outcome of isolated locoregional recurrence in patients with breast cancer according to their primary local treatment. Clin Breast Cancer. 2014;14(3):198–204.

    PubMed  Article  Google Scholar 

  45. 45.

    Giordano SH, Buzdar AU, Smith TL, et al. Is breast cancer survival improving? Cancer. 2004;100(1):44–52.

    PubMed  Article  Google Scholar 

  46. 46.

    Dellapasqua S, Bagnardi V, Balduzzi A et al. Outcomes of patients with breast cancer who present with ipsilateral supraclavicular or internal mammary lymph node metastases. Clin Breast Cancer. 2014;14(1):53–60.

    PubMed  Article  Google Scholar 

  47. 47.

    Aebi S, Gelber S, Anderson SJ, et al. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. The Lancet Oncology. 2014;15(2):156–63.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgment

This work was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5 × 1000 funds. We acknowledge Claudia Crovace for her support in editing this manuscript, and Maria Grazia Villardita for her editorial assistance.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Francesca Magnoni MD, PhD.

Ethics declarations

Disclosure

The authors declare 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.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

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

Verify currency and authenticity via CrossMark

Cite this article

Magnoni, F., Colleoni, M., Mattar, D. et al. Contralateral Axillary Lymph Node Metastases from Breast Carcinoma: Is it Time to Review TNM Cancer Staging?. Ann Surg Oncol 27, 4488–4499 (2020). https://doi.org/10.1245/s10434-020-08605-4

Download citation