Evidence map›Paper›PMID 39317942›Full record

Trial reportBreast cancer research : BCR2024

On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer.

Bruno Valentin Sinn, Katharina Sychra, Michael Untch, Thomas Karn, Marion van Mackelenbergh, Jens Huober, Wolfgang Schmitt, Frederik Marmé, Christian Schem, Christine Solbach and 9 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Breast cancer research : BCR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Trial
  2. Review
  3. Review
  4. Review
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Bruno Valentin SinnDepartment of Pathology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany. bruno.sinn@web.de.ORCID 0000-0002-1257-9799
Katharina SychraDepartment of Pathology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
Michael UntchDepartment of Gynecology, Helios Kliniken Berlin-Buch, Berlin, Germany.
Thomas KarnDepartment of Gynecology and Obstetrics, Goethe-University, Frankfurt, Germany.
Marion van MackelenberghDepartment of Gynecology and Obstetrics, Universitätsklinikum Schleswig-Holstein, Kiel, Germany.
Jens HuoberBreast Center St. Gallen, Kantonsspital St. Gallen, St. Gallen, Switzerland.
Wolfgang SchmittDepartment of Pathology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
Frederik MarméDepartment of Gynecologic Oncology, Medical Faculty Mannheim, Heidelberg University, University Hospital Mannheim, Mannheim, Germany.
Christian SchemMammazentrum Hamburg, Hamburg, Germany.
Christine SolbachBreast Center, Universitätsklinikum Frankfurt, Frankfurt, Germany.
Elmar StickelerDepartment of Gynecology, Uniklinik RWTH Aachen, Aachen, Germany.
Hans TeschCentrum für Hämatologie und Onkologie Bethanien, Frankfurt am Main, Germany.
Peter A FaschingDepartment of Gynecology and Obstetrics, University Hospital Erlangen, Erlangen, Germany.
Andreas SchneeweissUniversitätsfrauenklinik Heidelberg, Heidelberg, Germany.
Volkmar MüllerDepartment of Gynecology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Johannes HoltschmidtGerman Breast Group, Neu-Isenburg, Germany.
Valentina NekljudovaGerman Breast Group, Neu-Isenburg, Germany.
Sibylle LoiblGerman Breast Group, Neu-Isenburg, Germany.
Carsten DenkertDepartment of Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), Marburg, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPatients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies.

methodsOn-treatment biopsies from 297 patients with invasive BC in three randomized, prospective neoadjuvant trials were assessed (GeparQuattro, GeparQuinto, GeparSixto). BC quantity, tumor-infiltrating lymphocytes (TILs), and the proliferation marker Ki-67 were compared to pre-treatment samples. The study investigated the correlation between residual cancer, changes in Ki-67 and TILs, and their impact on pathologic complete response (pCR) and disease-free survival (DFS).

resultsAmong the 297 samples, 138 (46%) were hormone receptor-positive (HR+)/human epidermal growth factor 2-negative (HER2-), 87 (29%) were triple-negative (TNBC), and 72 (24%) were HER2+. Invasive tumor cells were found in 70% of on-treatment biopsies, with varying rates across subtypes (HR+/HER2-: 84%, TNBC: 62%, HER2+: 51%; p < 0.001). Patients with residual tumor on-treatment had an 8% pCR rate post-treatment (HR+/HER2-: 3%, TNBC: 19%, HER2+: 11%), while those without any invasive tumor had a 50% pCR rate (HR+/HER2-: 27%; TNBC: 48%, HER2+: 66%). Sensitivity for predicting residual disease was 0.81, with positive and negative predictive values of 0.92 and 0.50, respectively. Increasing TILs from baseline to on-treatment biopsy (if residual tumor was present) were linked to higher pCR likelihood in the overall cohort (OR 1.034, 95% CI 1.013-1.056 per % increase; p = 0.001) and with a longer DFS in TNBC (HR 0.980, 95% CI 0.963-0.997 per % increase; p = 0.026). Persisting or increased Ki-67 was associated with with lower pCR probability in the overall cohort (OR 0.957, 95% CI 0.928-0.986; p = 0.004) and shorter DFS in TNBC (HR 1.023, 95% CI 1.001-1.047; p = 0.04).

conclusionOn-treatment biopsies can predict patients unlikely to achieve pCR post-therapy. This could facilitate therapy adjustments for TNBC or HER2 + BC. They also might offer insights into therapy resistance mechanisms. Future research should explore whether standardized or expanded sampling enhances the accuracy of on-treatment biopsy procedures. Trial registration GeparQuattro (EudraCT 2005-001546-17), GeparQuinto (EudraCT 2006-005834-19) and GeparSixto (EudraCT 2011-000553-23).

Indexed as

Breast NeoplasmsErb-b2 Receptor Tyrosine KinasesLymphocytes, Tumor-InfiltratingNeoadjuvant TherapyAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBiopsyChemotherapy, AdjuvantDisease-Free SurvivalFemaleHumansKi-67 AntigenMiddle AgedNeoplasm, ResidualBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesKi-67 AntigenReceptors, EstrogenReceptors, ProgesteroneBreast cancerKi-67Neoadjuvant therapySerial biopsiesTILs

Identifiers

PMID39317942
PMCPMC11423510

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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.