Evidence map›Paper›PMID 42250186›Full record

ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026

Evaluating total tumor load (TTL) to predict metastasis in four or more axillary lymph nodes in HR +/HER2- breast cancer patients: the TULIP4N + study.

Esther Zamora, Antonio Piñero-Madrona, Isabella Sperduti, Anna Sapino, José Luis Fougo, Vicente Peg

Abstract readMulticenter Study
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In one paragraph

Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Esther ZamoraMedical Oncology Department, Vall d'Hebron University Hospital-Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Antonio Piñero-MadronaBreast Surgery Unit, Virgen de la Arrixaca University Hospital, Murcia, Spain.
Isabella SperdutiBiostatistics Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy.
Anna SapinoCandiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy.
José Luis FougoDepartment of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
Vicente PegPathology Department, Vall d'Hebron University Hospital, Barcelona, Spain. vicente.peg@vallhebron.cat.ORCID http://orcid.org/0000-0002-5203-6166

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeTo validate the predictive value of Total Tumor Load (TTL), based on Cytokeratin 19 (CK19) mRNA copy number measured by OSNA in sentinel lymph nodes (SLNs), and to establish an optimal cut-off for identifying HR + /HER2- breast cancer (BC) patients at high risk of ≥ 4 metastatic lymph nodes (LNs), eligible for adjuvant abemaciclib therapy. PATIENTS/

methodsA retrospective, international, multicenter study pooling data from six studies conducted between 2000 and 2016 in adult BC patients with SLN biopsies analyzed by OSNA. Variables were TTL (CK19 mRNA copies/µL) in SLNs, number of LNs removed, and number of metastatic ones. We constructed receiver operating characteristics (ROC) curves to determine optimal TTL values and multivariate logistic regression models to identify relevant prognostic factors for predicting ≥ 4 LN metastases.

resultsWe included 3804 patients with HR + /HER2- tumors of any histological type, complete axillary LN dissection, and > 4 LNs removed; 608 (16.0%) had ≥ 4 metastatic LNs and 439 had lobular BC. At cut-offs of 99,500 and 101,000 copies/µL, TTL had a 32.3% and 32.4% PPV. In lobular BC, cut-offs between 92,305 and 108,700 copies/µL reached a 40% PPV. In lobular HR + /HER2- BC, a multivariate model including tumor grade, TTL, and lymphovascular invasion reached a 49% PPV for predicting ≥ 4 metastatic LNs, yielding a nomogram and an online calculator for use in routine practice.

conclusionTTL measured using OSNA predicts ≥ 4 metastatic LNs in patients with luminal-like BC, with a proposed optimal threshold of 100,000 copies/µL.

trial registrationNot applicable.

Indexed as

Breast NeoplasmsSentinel Lymph NodeTumor BurdenAdultAgedAxillaErb-b2 Receptor Tyrosine KinasesFemaleHumansKeratin-19Lymphatic MetastasisLymph NodesMiddle AgedPredictive Value of TestsPrognosisReceptors, EstrogenERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesKeratin-19KRT19 protein, humanReceptors, EstrogenReceptors, ProgesteroneRNA, MessengerAbemaciclibBreast cancerLymph node metastasisOSNASentinel lymph nodeTotal tumor load

Identifiers

PMID42250186

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.