Regional lymph node involvement among patients with de novo metastatic breast cancer Journal Article


Authors: Bitencourt, A.; Rossi Saccarelli, C.; Morris, E. A.; Flynn, J.; Zhang, Z.; Khan, A.; Gillespie, E.; Cahlon, O.; Mueller, B.; Cuaron, J. J.; McCormick, B.; Powell, S. N.; Plitas, G.; Razavi, P.; Pinker, K.; Riedl, C. C.; Sutton, E. J.; Braunstein, L. Z.
Article Title: Regional lymph node involvement among patients with de novo metastatic breast cancer
Abstract: Importance: Regional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear. Objective: To determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation. Design, Setting, and Participants: This cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography-computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020. Exposures: Untreated metastatic breast cancer. Main Outcome and Measures: The primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings. Results: Among 597 women (median [interquartile range] age, 53 [44-65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor-negative tumors (92.4%) than estrogen receptor-positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival. Conclusions and Relevance: These findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.
Journal Title: JAMA Network Open
Volume: 3
Issue: 10
ISSN: 2574-3805
Publisher: American Medical Association  
Date Published: 2020-10-01
Start Page: e2018790
Language: English
DOI: 10.1001/jamanetworkopen.2020.18790
PUBMED: 33034638
PROVIDER: scopus
PMCID: PMC7547365
DOI/URL:
Notes: Article -- Export Date: 2 November 2020 -- Source: Scopus
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MSK Authors
  1. Zhigang Zhang
    431 Zhang
  2. Simon Nicholas Powell
    335 Powell
  3. Christopher Riedl
    60 Riedl
  4. Boris A Mueller
    104 Mueller
  5. Elizabeth A Morris
    341 Morris
  6. Oren Cahlon
    158 Cahlon
  7. George Plitas
    107 Plitas
  8. Beryl McCormick
    372 McCormick
  9. Elizabeth Jane Sutton
    71 Sutton
  10. John Jacob Cuaron
    143 Cuaron
  11. Pedram Razavi
    184 Razavi
  12. Atif Jalees Khan
    155 Khan
  13. Jessica Flynn
    182 Flynn
  14. Erin Faye Gillespie
    149 Gillespie