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HER2-low triple-negative breast cancer (TNBC) shows distinct biological features, including higher androgen receptor expression. HER2-zero TNBC is linked to BRCA mutations and higher proliferation, suggesting different therapeutic strategies may be needed.

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Area of Science:

  • Oncology
  • Pathology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) is aggressive with poor prognosis and heterogeneity.
  • HER2-low classification is a potential therapeutic target, but its significance in TNBC is unclear.

Purpose of the Study:

  • To investigate the clinical and biological significance of HER2-low versus HER2-zero TNBC.
  • To compare clinicopathological features and treatment responses between HER2-low and HER2-zero TNBC subgroups.

Main Methods:

  • Retrospective analysis of 195 primary TNBC patients.
  • Collected data on histology, AR, BRCA, Ki-67, PD-L1, TILs, and treatment response.
  • Classified tumors as HER2-low (IHC 1+/2+ & FISH-) or HER2-zero (IHC 0).

Main Results:

  • 38% of TNBC cases were HER2-low, 62% were HER2-zero.
  • HER2-low tumors showed higher rates of apocrine carcinoma and AR positivity.
  • HER2-zero tumors had higher BRCA mutations, Ki-67, and PD-L1 positivity.

Conclusions:

  • HER2-low and HER2-zero TNBC are biologically distinct subgroups.
  • HER2-low TNBC is enriched for luminal AR-like features; HER2-zero TNBC exhibits basal-like, proliferative, and immunogenic features.
  • Different therapeutic approaches may be required for these subgroups, warranting further investigation.