TY - JOUR
T1 - STAT3 activation in HER2-positive breast cancers
T2 - Analysis of data from a large prospective trial
AU - Sonnenblick, Amir
AU - Agbor-tarh, Dominique
AU - de Azambuja, Evandro
AU - Hultsch, Susanne
AU - Izquierdo, Miguel
AU - Liu, Minetta
AU - Pruneri, Giancarlo
AU - Harbeck, Nadia
AU - Piccart, Martine
AU - Moreno-Aspita, Alvaro
AU - Granit, Roy Zvi
AU - Rouas, Ghizlane
AU - Fahoum, Ibrahim
AU - Sotiriou, Christos
N1 - Publisher Copyright:
© 2020 Union for International Cancer Control
PY - 2021/3/15
Y1 - 2021/3/15
N2 - The JAK/STAT3 signaling pathway may be aberrantly activated and have various and conflicting roles in breast cancer. The current study explored prognostic implications of activated STAT3 in human epidermal growth factor receptor 2 (HER2)-positive primary breast cancers in the context of a large prospective study (ALTTO). Activated STAT3 was determined by immunohistochemical analysis of STAT3 phosphorylation (Y705) performed on the primary tumors. This analysis evaluated whether patients with activated STAT3 had disease-free survival (DFS) and overall survival (OS) different from patients without activated STAT3. A total of 5694 patients out of the 8381 patients enrolled in ALTTO were included in this analysis (67.9%), and 2634 of them (46%) had evidence of STAT3 activation (minimum tumor Allred score ≥2). The median follow-up was 6.93 years (6.85-6.97 years), at the end of which 1035 (18.18%) and 520 (9.13%) patients experienced DFS and OS events, respectively. Patients with STAT3 activation experienced improved DFS compared to those without it (multivariable hazard ratio [HR], 0.84; 95% confidence interval [CI] 0.74-0.95; P =.006). There were no group differences in OS (multivariable HR, 0.92; 95% CI 0.78-1.10; P =.37). This effect was limited to ER-positive tumors. In conclusion, these findings support the role of STAT3 activation as a marker of favorable outcome in ER-positive/HER2-positive breast cancer patients.
AB - The JAK/STAT3 signaling pathway may be aberrantly activated and have various and conflicting roles in breast cancer. The current study explored prognostic implications of activated STAT3 in human epidermal growth factor receptor 2 (HER2)-positive primary breast cancers in the context of a large prospective study (ALTTO). Activated STAT3 was determined by immunohistochemical analysis of STAT3 phosphorylation (Y705) performed on the primary tumors. This analysis evaluated whether patients with activated STAT3 had disease-free survival (DFS) and overall survival (OS) different from patients without activated STAT3. A total of 5694 patients out of the 8381 patients enrolled in ALTTO were included in this analysis (67.9%), and 2634 of them (46%) had evidence of STAT3 activation (minimum tumor Allred score ≥2). The median follow-up was 6.93 years (6.85-6.97 years), at the end of which 1035 (18.18%) and 520 (9.13%) patients experienced DFS and OS events, respectively. Patients with STAT3 activation experienced improved DFS compared to those without it (multivariable hazard ratio [HR], 0.84; 95% confidence interval [CI] 0.74-0.95; P =.006). There were no group differences in OS (multivariable HR, 0.92; 95% CI 0.78-1.10; P =.37). This effect was limited to ER-positive tumors. In conclusion, these findings support the role of STAT3 activation as a marker of favorable outcome in ER-positive/HER2-positive breast cancer patients.
KW - ALTTO
KW - HER2
KW - STAT3
KW - breast cancer
KW - estrogen receptor
UR - http://www.scopus.com/inward/record.url?scp=85096745899&partnerID=8YFLogxK
U2 - 10.1002/ijc.33385
DO - 10.1002/ijc.33385
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C2 - 33152119
AN - SCOPUS:85096745899
SN - 0020-7136
VL - 148
SP - 1529
EP - 1535
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 6
ER -
