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Reactive stroma and trastuzumab resistance in HER2‐positive early breast cancer
Author(s) -
Sonnenblick Amir,
SalmonDivon Mali,
Salgado Roberto,
Dvash Efrat,
Pondé Noam,
Zahavi Tamar,
Salmon Asher,
Loibl Sibylle,
Denkert Carsten,
Joensuu Heikki,
Ameye Lieveke,
Van den Eynden Gert,
KellokumpuLehtinen PirkkoLiisa,
Azaria Amos,
Loi Sherene,
Michiels Stefan,
Richard François,
Sotiriou Christos
Publication year - 2020
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32859
Subject(s) - trastuzumab , breast cancer , stroma , stromal cell , medicine , oncology , tamoxifen , cancer , breast disease , cancer research , pathology , immunohistochemistry
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.