Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer
AuthorSonnenblick, A; Salmon-Divon, M; Salgado, R; Dvash, E; Ponde, N; Zahavi, T; Salmon, A; Loibl, S; Denkert, C; Joensuu, H; ...
Source TitleInternational Journal of Cancer
University of Melbourne Author/sLoi, Sherene
AffiliationSir Peter MacCallum Department of Oncology
Document TypeJournal Article
CitationsSonnenblick, A., Salmon-Divon, M., Salgado, R., Dvash, E., Ponde, N., Zahavi, T., Salmon, A., Loibl, S., Denkert, C., Joensuu, H., Ameye, L., Van den Eynden, G., Kellokumpu-Lehtinen, P. -L., Azaria, A., Loi, S., Michiels, S., Richard, F. & Sotiriou, C. (2020). Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer. INTERNATIONAL JOURNAL OF CANCER, 147 (1), pp.266-276. https://doi.org/10.1002/ijc.32859.
Access StatusAccess this item via the Open Access location
Open Access URLPublished version
We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy. The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival. Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N = 209) were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (hazard ratio [HR] = 1.27 p interaction = 0.014 [DCN], HR = 1.58, p interaction = 0.027 [PLAU], HR = 1.71, p interaction = 0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR = 0.73 p interaction = 0.47 [DCN], HR = 0.71, p interaction = 0.73 [PLAU], HR = 0.84; p interaction = 0.36 [HER2STROMA]). Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC <50%). In conclusion, reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy.
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