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Cited by 1,026

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2–Positive and Triple-Negative Primary Breast Cancers

Open access
Denkert, Carsten, von Minckwitz, Gunter, Brase, Jan C., Sinn, Bruno V., Gade, Stephan, Kronenwett, Ralf, Pfitzner, Berit M., Salat, Christoph, Loi, Sherene, Schmitt, Wolfgang D., Schem, Christian, Fisch, Karin, Darb-Esfahani, Silvia, Mehta, Keyur, Sotiriou, Christos, Wienert, Stephan, Klare, Peter, André, Fabrice, Klauschen, Frederick, Blohmer, Jens-Uwe, Krappmann, Kristin, Schmidt, Marcus, Tesch, Hans, Kümmel, Sherko, Sinn, Peter, Jackisch, Christian, Dietel, Manfred, Reimer, Toralf, Untch, Michael, Loibl, Sibylle·2015·Journal of Clinical Oncology
DOI 10.1200/jco.2014.58.1967
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Abstract

Purpose: Modulation of immunologic interactions in cancer tissue is a promising therapeutic strategy. To investigate the immunogenicity of human epidermal growth factor receptor 2 (HER2) –positive and triple-negative (TN) breast cancers (BCs), we evaluated tumor-infiltrating lymphocytes (TILs) and immunologically relevant genes in the neoadjuvant GeparSixto trial. Patients and Methods: GeparSixto investigated the effect of adding carboplatin (Cb) to an anthracycline-plus-taxane combination (PM) on pathologic complete response (pCR). A total of 580 tumors were evaluated before random assignment for stromal TILs and lymphocyte-predominant BC (LPBC). mRNA expression of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) as well as immunosuppressive factors (IDO1, PD-1, PD-L1, CTLA4, FOXP3) was measured in 481 tumors. Results: Increased levels of stromal TILs predicted pCR in univariable (P < .001) and multivariable analyses (P < .001). pCR rate was 59.9% in LPBC and 33.8% for non-LPBC (P < .001). pCR rates ≥ 75% were observed in patients with LPBC tumors treated with PMCb, with a significant test for interaction with therapy in the complete (P = .002) and HER2-positive (P = .006), but not the TNBC, cohorts. Hierarchic clustering of mRNA markers revealed three immune subtypes with different pCR rates (P < .001). All 12 immune mRNA markers were predictive for increased pCR. The highest odds ratios (ORs) were observed for PD-L1 (OR, 1.57; 95% CI, 1.34 to 1.86; P < .001) and CCL5 (OR, 1.41; 95% CI, 1.23 to 1.62; P < .001). Conclusion: Immunologic factors were highly significant predictors of therapy response in the GeparSixto trial, particularly in patients treated with Cb. After further standardization, they could be included in histopathologic assessment of BC.

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Authors
Denkert, C., von Minckwitz, G., Brase, J. C., Sinn, B. V., Gade, S., Kronenwett, R., Pfitzner, B. M., Salat, C., Loi, S., Schmitt, W. D., Schem, C., Fisch, K., Darb-Esfahani, S., Mehta, K., Sotiriou, C., Wienert, S., Klare, P., André, F., Klauschen, F., Blohmer, J.-U., Krappmann, K., Schmidt, M., Tesch, H., Kümmel, S., Sinn, P., Jackisch, C., Dietel, M., Reimer, T., Untch, M., & Loibl, S.
Venue
Journal of Clinical Oncology
Publisher
American Society of Clinical Oncology (ASCO)
Published
2015-03-20
Volume
33
Issue
9
Pages
983-991
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
DOI
10.1200/jco.2014.58.1967
OpenAlex
W2125885282
Cited by
1,026
References
5
FWCI
26.73
Type
journal article
Language
en
Open access
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