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Expression of epithelial-mesenchymal transition driver brachyury and status of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in predicting treatment responses to neoadjuvant chemotherapy of breast cancer.

Abstract Brachyury has been characterized as a driver of epithelial-mesenchymal transition process which is regarded as an important mechanism of cancer cell invasion and metastatic progression. The status of tumor-infiltrating lymphocytes has been proposed to predict response to neoadjuvant chemotherapy in breast cancer. We investigated the clinical significance and value of tumor-infiltrating lymphocytes and brachyury as biomarkers to predict treatment responses to neoadjuvant chemotherapy in breast cancer. We also examined the correlation of the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly predict long-term outcome. This retrospective study included a series of 44 consecutive patients treated between January 2011 and December 2015. All patient samples were obtained using core needle biopsy before neoadjuvant chemotherapy. The relationship of expression of Brachyury and tumor-infiltrating lymphocyte subsets (CD8+, forkhead box protein 3 tumor-infiltrating lymphocytes) with clinicopathological factors was assessed to identify its predictive role with respect to tumor response to neoadjuvant chemotherapy and the outcome. Of 44 patients, 6 showed no response, 31 had partial response, and 7 demonstrated pathological complete response. Forkhead box protein 3 was significantly higher in the response group than in the no response group (no response = 2.6, partial response = 7.0, complete response = 9.7, p = 0.020). Brachyury expression was inversely associated with response to neoadjuvant chemotherapy, but the difference was not statistically significant ( p = 0.62). We also observed a significant association between forkhead box protein 3 ( p = 0.001) and the Neo-Bioscore, while only a marginal difference was observed with CD8+ expression ( p = 0.074). This study demonstrated that forkhead box protein 3 expression has value as the only independent marker that predicts a good response to neoadjuvant chemotherapy and that it is related with a good prognosis according to the Neo-Bioscore. Brachyury was significantly associated with estrogen receptor positive and human epidermal growth factor receptor 2 negative status; further study would be needed to clarify how it affects treatment prognosis.
PMID
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Authors

Mayor MeshTerms
Keywords

Brachyury

CD8+/forkhead box protein 3 ratio

Neo-Bioscore

epithelial–mesenchymal transition

tumor-infiltrating lymphocyte

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28621227
OWN - NLM
STAT- MEDLINE
DA  - 20170616
DCOM- 20170622
LR  - 20170622
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 6
DP  - 2017 Jun
TI  - Expression of epithelial-mesenchymal transition driver brachyury and status of
      tumor-infiltrating CD8+ and FOXP3+ lymphocytes in predicting treatment responses 
      to neoadjuvant chemotherapy of breast cancer.
PG  - 1010428317710575
LID - 10.1177/1010428317710575 [doi]
AB  - Brachyury has been characterized as a driver of epithelial-mesenchymal transition
      process which is regarded as an important mechanism of cancer cell invasion and
      metastatic progression. The status of tumor-infiltrating lymphocytes has been
      proposed to predict response to neoadjuvant chemotherapy in breast cancer. We
      investigated the clinical significance and value of tumor-infiltrating
      lymphocytes and brachyury as biomarkers to predict treatment responses to
      neoadjuvant chemotherapy in breast cancer. We also examined the correlation of
      the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly 
      predict long-term outcome. This retrospective study included a series of 44
      consecutive patients treated between January 2011 and December 2015. All patient 
      samples were obtained using core needle biopsy before neoadjuvant chemotherapy.
      The relationship of expression of Brachyury and tumor-infiltrating lymphocyte
      subsets (CD8+, forkhead box protein 3 tumor-infiltrating lymphocytes) with
      clinicopathological factors was assessed to identify its predictive role with
      respect to tumor response to neoadjuvant chemotherapy and the outcome. Of 44
      patients, 6 showed no response, 31 had partial response, and 7 demonstrated
      pathological complete response. Forkhead box protein 3 was significantly higher
      in the response group than in the no response group (no response = 2.6, partial
      response = 7.0, complete response = 9.7, p = 0.020). Brachyury expression was
      inversely associated with response to neoadjuvant chemotherapy, but the
      difference was not statistically significant ( p = 0.62). We also observed a
      significant association between forkhead box protein 3 ( p = 0.001) and the
      Neo-Bioscore, while only a marginal difference was observed with CD8+ expression 
      ( p = 0.074). This study demonstrated that forkhead box protein 3 expression has 
      value as the only independent marker that predicts a good response to neoadjuvant
      chemotherapy and that it is related with a good prognosis according to the
      Neo-Bioscore. Brachyury was significantly associated with estrogen receptor
      positive and human epidermal growth factor receptor 2 negative status; further
      study would be needed to clarify how it affects treatment prognosis.
FAU - Lee, Kwan Ho
AU  - Lee KH
AD  - 1 Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School
      of Medicine, Seoul, Korea.
FAU - Kim, Eun Young
AU  - Kim EY
AD  - 1 Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School
      of Medicine, Seoul, Korea.
FAU - Park, Yong Lai
AU  - Park YL
AD  - 1 Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School
      of Medicine, Seoul, Korea.
FAU - Do, Sung-Im
AU  - Do SI
AD  - 2 Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University
      School of Medicine, Seoul, Korea.
FAU - Chae, Seoung Wan
AU  - Chae SW
AD  - 2 Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University
      School of Medicine, Seoul, Korea.
FAU - Park, Chan Heun
AU  - Park CH
AD  - 1 Department of Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School
      of Medicine, Seoul, Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Brachyury protein)
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Fetal Proteins)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (T-Box Domain Proteins)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers, Tumor/genetics
MH  - Breast Neoplasms/*drug therapy/genetics/pathology
MH  - CD8-Positive T-Lymphocytes/*metabolism
MH  - Epithelial-Mesenchymal Transition/*drug effects
MH  - Female
MH  - Fetal Proteins/*biosynthesis/genetics
MH  - Forkhead Transcription Factors/*genetics
MH  - Humans
MH  - Lymphocytes, Tumor-Infiltrating/metabolism/pathology
MH  - Middle Aged
MH  - Neoadjuvant Therapy
MH  - Prognosis
MH  - Receptor, ErbB-2/genetics
MH  - T-Box Domain Proteins/*biosynthesis/genetics
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Brachyury
OT  - CD8+/forkhead box protein 3 ratio
OT  - Neo-Bioscore
OT  - epithelial-mesenchymal transition
OT  - tumor-infiltrating lymphocyte
EDAT- 2017/06/18 06:00
MHDA- 2017/06/24 06:00
CRDT- 2017/06/17 06:00
AID - 10.1177/1010428317710575 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Jun;39(6):1010428317710575. doi: 10.1177/1010428317710575.