Prediction of high nodal burden in patients with sentinel node-positive luminal ERBB2-negative breast cancerDepartment of Surgery, Västmanland Hospital, Västeras, Sweden; Centre for Clinical Research Uppsala University, Västmanland Hospital Västerås, Sweden.
Centre for Clinical Research Uppsala University, Västmanland Hospital Västerås, Sweden.
Department of Plastic and Breast Surgery, Aarhus University Hosoital, Denmark.
Department of Breast Surgery, Gentofte Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Breast Center Karolinska, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden.
Università Vita-Salute San Raffaele, Milano, Italy; IRCCS Ospedale San Raffaele, Milano, Italy.
1st Department of Surgery, National and Kapodistrian University of Athens, Laiko Hospital, Athens, Greece.
Interdisciplinary Breast Center, University of Ulm, Ulm, Germany; Breast Center Die Filderklinik, Filderstadt, Germany.
Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Oncology, Aarhus University Hospital, Aarhus, Denmark; Aarhus University, Faculty of Health, Aarhus, Denmark.
Sahlgrenska Center for Cancer Research, Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany.
Division of Oncology, Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Surgery and Gastroenterology, Skane University Hospital, Lund, Sweden.
Breast Center Karolinska, Karolinska Comprehensive Cancer Center, Karolinska University Hospital, Stockholm, Sweden; Department of Surgery, Capio St Göran's Hospital, Stockholm, Sweden.
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2024 (English)In: JAMA Surgery, ISSN 2168-6254, E-ISSN 2168-6262, Vol. 159, no 12, p. E1-E10Article in journal (Refereed) Published
Abstract [en]
Importance: In patients with clinically node-negative (cN0) breast cancer and 1 or 2 sentinel lymph node (SLN) macrometastases, omitting completion axillary lymph node dissection (CALND) is standard. High nodal burden (≥4 axillary nodal metastases) is an indication for intensified treatment in luminal breast cancer; hence, abstaining from CALND may result in undertreatment.
Objective: To develop a prediction model for high nodal burden in luminal ERBB2-negative breast cancer (all histologic types and lobular breast cancer separately) without CALND.
Design, Setting, and Participants: The prospective Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases (SENOMAC) trial randomized patients 1:1 to CALND or its omission from January 2015 to December 2021 among adult patients with cN0 T1-T3 breast cancer and 1 or 2 SLN macrometastases across 5 European countries. The cohort was randomly split into training (80%) and test (20%) sets, with equal proportions of high nodal burden. Prediction models were developed by multivariable logistic regression in the complete luminal ERBB2-negative cohort and a lobular breast cancer subgroup. Nomograms were constructed. The present diagnostic/prognostic study presents the results of a prespecified secondary analysis of the SENOMAC trial. Herein, only patients with luminal ERBB2-negative tumors assigned to CALND were selected. Data analysis for this article took place from June 2023 to April 2024.
Exposure: Predictors of high nodal burden.
Main Outcomes and Measures: High nodal burden was defined as ≥4 axillary nodal metastases. The luminal prediction model was evaluated regarding discrimination and calibration.
Results: Of 1010 patients (median [range] age, 61 [34-90] years; 1006 [99.6%] female and 4 [0.4%] male), 138 (13.7%) had a high nodal burden and 212 (21.0%) had lobular breast cancer. The model in the training set (n = 804) included number of SLN macrometastases, presence of SLN micrometastases, SLN ratio, presence of SLN extracapsular extension, and tumor size (not included in lobular subgroup). Upon validation in the test set (n = 201), the area under the receiver operating characteristic curve (AUC) was 0.74 (95% CI, 0.62-0.85) and the calibration was satisfactory. At a sensitivity threshold of ≥80%, all but 5 low-risk patients were correctly classified corresponding to a negative predictive value of 94%. The prediction model for the lobular subgroup reached an AUC of 0.74 (95% CI, 0.66-0.83).
Conclusions and Relevance: The predictive models and nomograms may facilitate systemic treatment decisions without exposing patients to the risk of arm morbidity due to CALND. External validation is needed.
Trial Registration: ClinicalTrials.gov Identifier: NCT02240472.
Place, publisher, year, edition, pages
American Medical Association (AMA), 2024. Vol. 159, no 12, p. E1-E10
National Category
Surgery Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-232281DOI: 10.1001/jamasurg.2024.3944ISI: 001328636700009PubMedID: 39320882Scopus ID: 2-s2.0-85209767652OAI: oai:DiVA.org:umu-232281DiVA, id: diva2:1916719
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Society of MedicineThe Breast Cancer FoundationFamiljen Erling-Perssons Stiftelse2024-11-282024-11-282024-11-28Bibliographically approved