{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T06:49:16Z","timestamp":1772866156605,"version":"3.50.1"},"reference-count":24,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"2","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The prognostic significance of isolated tumor cells (ITCs) in lymph nodes remains uncertain, and immunohistochemistry (IHC) is not consistently used for their detection. We aimed to evaluate the clinical relevance of ITCs and assess whether omission of IHC leads to nodal understaging by comparing outcomes across node-negative patients with and without IHC-confirmed negativity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MATERIALS AND METHODS<\/jats:title>\n                    <jats:p>In this retrospective population-based cohort study, we analyzed SEER data from 2010 to 2015, including 127,494 women with invasive breast cancer. Nodal status was classified as N0, N0(i\u2013), N0(i+), or N1mi. Breast cancer\u2013specific survival (BCSS) was evaluated using univariable and multivariable Fine-Gray competing risk regression. Overall survival (OS) was assessed using univariable and multivariable flexible parametric survival models (FPSMs). Models were adjusted for age, tumor grade, histologic subtype, estrogen receptor\/progesterone receptor\/human epidermal growth factor receptor 2 status, T stage, race, surgery, chemotherapy, radiation, marital status, number of lymph nodes examined, and year of diagnosis. Subgroup analysis was performed among patients who received both chemotherapy and radiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Compared with N0(i\u2013), both N0(i+) and N0 were significantly associated with worse BCSS (adjusted subdistribution hazard ratio [SHR], 1.40 [95% CI, 1.23 to 1.60];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001 and 1.09 [95% CI, 1.03 to 1.16];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .003, respectively). N0(i+) also had worse BCSS than N0 (adjusted SHR, 1.28 [95% CI, 1.13 to 1.46];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001). For OS, N0(i+) and N0 showed higher mortality risks compared with N0(i\u2013) in the multivariable FPSM (HR, 1.15 [95% CI, 1.06 to 1.25];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .001 and 1.10 [95% CI, 1.07 to 1.14];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001, respectively), with no significant difference between N0(i+) and N0 (HR, 1.05 [95% CI, 0.97 to 1.13];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .26). In patients receiving both chemotherapy and radiation, N0(i+), compared with N0(i\u2013), remained associated with worse OS (HR, 1.26 [95% CI, 1.02 to 1.56];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .03), whereas BCSS differences were not statistically significant.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>ITCs are associated with worse BCSS and OS despite classification as node-negative. Omitting IHC may obscure their detection. Incorporating IHC into routine nodal evaluation may enhance prognostic assessment and guide treatment decisions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-25-00974","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T20:59:20Z","timestamp":1771016360000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Significance of Isolated Tumor Cells and the Role of Immunohistochemistry in Nodal Evaluation in Breast Cancer: A SEER-Based Analysis and Reappraisal"],"prefix":"10.1200","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7413-1810","authenticated-orcid":true,"given":"Seyed Reza","family":"Taha","sequence":"first","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1921-081X","authenticated-orcid":true,"given":"Fouad","family":"Boulos","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"e_1_3_4_2_2","volume-title":"AJCC Cancer Staging Manual","author":"Frederick L","year":"2002","unstructured":"Frederick L, Page DL, Fleming ID, et al: AJCC Cancer Staging Manual. 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