Inactive immune pathways in triple negative breast cancers that showed resistance to neoadjuvant chemotherapy as

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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
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Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model

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Takeshi Sawada1,2, Riet Hilhorst3, Savithri Rangarajan3

  • 1Shien-Lab, National Cancer Center Hospital, Tokyo, Japan.

Oncotarget
|October 23, 2018
PubMed

Insights

Triple negative breast cancer (TNBC) patients resistant to neoadjuvant chemotherapy (NAC) show lower activity in immune-related kinases and fewer tumor-infiltrating lymphocytes (TILs). This suggests the immune system is less active and not stimulated by NAC in non-responders.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Triple negative breast cancer (TNBC) is an aggressive subtype.
  • About 5% of TNBC patients receiving neoadjuvant chemotherapy (NAC) experience progressive disease (PD).
  • TNBCs with PD during NAC are understudied compared to responders.

Purpose of the Study:

  • To investigate kinase activity profiles in TNBC non-responders to NAC.
  • To explore biological differences underlying lack of response to NAC in TNBC.
  • To compare kinase activity and immune cell infiltration between non-responders and controls.

Main Methods:

  • Analysis of 740 TNBC cases to identify 20 non-responders to NAC.
  • Evaluation of 7 non-responders and 10 control TNBCs (no NAC).
  • Determination of tyrosine kinase activity profiles using a peptide microarray system.
  • Assessment of tumor-infiltrating lymphocytes (TILs).

Main Results:

  • No correlation between NAC response and clinical factors (age, menopausal status, tumor size, lymph node status).
  • 35 peptides showed significantly lower phosphorylation in non-responders (p < 0.05).
  • ZAP70, LCK, SYK, and JAK2 identified as differentially active upstream kinases.
  • Lower activity in immune-related pathways and significantly fewer TILs observed in non-responders (p = 0.0053).

Conclusions:

  • Kinases related to the immune system are less activated in TNBC non-responders to NAC.
  • The immune system appears less active in non-responders and is not activated by NAC treatment.
  • These findings highlight potential immune-based biomarkers for NAC response in TNBC.
Keywords:
neoadjuvant chemotherapypeptide micro arraytriple negative breast cancertumor infiltrating lymphocytestyrosine kinase activity

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