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

  1. Sinn, Bruno Valentin ORCID logo
  2. Sychra, Katharina
  3. Untch, Michael
  4. Karn, Thomas
  5. van Mackelenbergh, Marion
  6. Huober, Jens
  7. Schmitt, Wolfgang
  8. Marmé, Frederik
  9. Schem, Christian
  10. Solbach, Christine
  11. Stickeler, Elmar
  12. Tesch, Hans
  13. Fasching, Peter A.
  14. Schneeweiss, Andreas
  15. Müller, Volkmar
  16. Holtschmidt, Johannes
  17. Nekljudova, Valentina
  18. Loibl, Sibylle
  19. Denkert, Carsten

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1000 Titel
  • On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer
1000 Autor/in
  1. Sinn, Bruno Valentin |
  2. Sychra, Katharina |
  3. Untch, Michael |
  4. Karn, Thomas |
  5. van Mackelenbergh, Marion |
  6. Huober, Jens |
  7. Schmitt, Wolfgang |
  8. Marmé, Frederik |
  9. Schem, Christian |
  10. Solbach, Christine |
  11. Stickeler, Elmar |
  12. Tesch, Hans |
  13. Fasching, Peter A. |
  14. Schneeweiss, Andreas |
  15. Müller, Volkmar |
  16. Holtschmidt, Johannes |
  17. Nekljudova, Valentina |
  18. Loibl, Sibylle |
  19. Denkert, Carsten |
1000 Verlag BioMed Central
1000 Erscheinungsjahr 2024
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2024-09-24
1000 Erschienen in
1000 Quellenangabe
  • 26(1):138
1000 Copyrightjahr
  • 2024
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s13058-024-01883-w |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11423510/ |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Patients 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.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>On-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).</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Among 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%; <jats:italic>p</jats:italic> &lt; 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; <jats:italic>p</jats:italic> = 0.001) and with a longer DFS in TNBC (HR 0.980, 95% CI 0.963–0.997 per % increase; <jats:italic>p</jats:italic> = 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; <jats:italic>p</jats:italic> = 0.004) and shorter DFS in TNBC (HR 1.023, 95% CI 1.001–1.047; <jats:italic>p</jats:italic> = 0.04).</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>On-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.</jats:p> <jats:p><jats:italic>Trial registration</jats:italic> GeparQuattro (EudraCT 2005-001546-17), GeparQuinto (EudraCT 2006-005834-19) and GeparSixto (EudraCT 2011-000553-23).</jats:p> </jats:sec>
1000 Sacherschließung
lokal Aged [MeSH]
lokal Receptor, ErbB-2/metabolism [MeSH]
lokal Breast cancer
lokal TILs
lokal Neoadjuvant Therapy/methods [MeSH]
lokal Neoadjuvant therapy
lokal Ki-67 Antigen/metabolism [MeSH]
lokal Chemotherapy, Adjuvant/methods [MeSH]
lokal Breast Neoplasms/mortality [MeSH]
lokal Breast Neoplasms/pathology [MeSH]
lokal Female [MeSH]
lokal Receptors, Estrogen/metabolism [MeSH]
lokal Adult [MeSH]
lokal Biopsy [MeSH]
lokal Receptors, Progesterone/metabolism [MeSH]
lokal Humans [MeSH]
lokal Treatment Outcome [MeSH]
lokal Breast Neoplasms/drug therapy [MeSH]
lokal Breast Neoplasms/metabolism [MeSH]
lokal Middle Aged [MeSH]
lokal Lymphocytes, Tumor-Infiltrating/metabolism [MeSH]
lokal Neoplasm, Residual/pathology [MeSH]
lokal Antineoplastic Combined Chemotherapy Protocols/therapeutic use [MeSH]
lokal Serial biopsies
lokal Lymphocytes, Tumor-Infiltrating/immunology [MeSH]
lokal Biomarkers, Tumor/metabolism [MeSH]
lokal Disease-Free Survival [MeSH]
lokal Research
lokal Prognosis [MeSH]
lokal Ki-67
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-1257-9799|https://frl.publisso.de/adhoc/uri/U3ljaHJhLCBLYXRoYXJpbmE=|https://frl.publisso.de/adhoc/uri/VW50Y2gsIE1pY2hhZWw=|https://frl.publisso.de/adhoc/uri/S2FybiwgVGhvbWFz|https://frl.publisso.de/adhoc/uri/dmFuIE1hY2tlbGVuYmVyZ2gsIE1hcmlvbg==|https://frl.publisso.de/adhoc/uri/SHVvYmVyLCBKZW5z|https://frl.publisso.de/adhoc/uri/U2NobWl0dCwgV29sZmdhbmc=|https://frl.publisso.de/adhoc/uri/TWFybcOpLCBGcmVkZXJpaw==|https://frl.publisso.de/adhoc/uri/U2NoZW0sIENocmlzdGlhbg==|https://frl.publisso.de/adhoc/uri/U29sYmFjaCwgQ2hyaXN0aW5l|https://frl.publisso.de/adhoc/uri/U3RpY2tlbGVyLCBFbG1hcg==|https://frl.publisso.de/adhoc/uri/VGVzY2gsIEhhbnM=|https://frl.publisso.de/adhoc/uri/RmFzY2hpbmcsIFBldGVyIEEu|https://frl.publisso.de/adhoc/uri/U2NobmVld2Vpc3MsIEFuZHJlYXM=|https://frl.publisso.de/adhoc/uri/TcO8bGxlciwgVm9sa21hcg==|https://frl.publisso.de/adhoc/uri/SG9sdHNjaG1pZHQsIEpvaGFubmVz|https://frl.publisso.de/adhoc/uri/TmVrbGp1ZG92YSwgVmFsZW50aW5h|https://frl.publisso.de/adhoc/uri/TG9pYmwsIFNpYnlsbGU=|https://frl.publisso.de/adhoc/uri/RGVua2VydCwgQ2Fyc3Rlbg==
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