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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

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Growth factor signalling and response to endocrine therapy: the Royal Marsden Experience

M Dowsett1, S Johnston, L-A Martin

  • 1Academic Department of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, UK. mitch.dowsett@icr.ac.uk

Endocrine-Related Cancer
|August 23, 2005
PubMed

Insights

Endocrine therapy resistance is common in ER-negative breast cancer. While most ER-positive breast cancers initially respond, resistance can develop, with HER2 status playing a role in tamoxifen response.

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • De novo resistance to endocrine therapy is nearly universal in estrogen receptor (ER)-negative breast cancer.
  • While many ER-positive breast cancers initially respond to tamoxifen or aromatase inhibitors, some exhibit resistance, indicating residual estrogen dependence.
  • HER2 positivity is linked to poor response rates with tamoxifen in neoadjuvant settings, but not with aromatase inhibitors.

Purpose of the Study:

  • To review the landscape of endocrine therapy resistance in breast cancer.
  • To explore the role of ER and HER2 status in response and resistance to endocrine therapies.
  • To highlight the paucity of data on acquired resistance to aromatase inhibitors.

Main Methods:

  • Review of existing clinical and preclinical data on endocrine therapy resistance in breast cancer.
  • Analysis of the association between HER2 status and response to tamoxifen and aromatase inhibitors.
  • Examination of molecular changes associated with acquired resistance to tamoxifen.

Main Results:

  • Acquired resistance to tamoxifen can occur with decreased ER positivity, but most recurrent lesions remain ER-positive.
  • A subset of tamoxifen-resistant tumors shows increased HER2 expression, potentially mediated by increased phospho-p38.
  • Limited clinical and biological data exist regarding acquired resistance to aromatase inhibitors.

Conclusions:

  • Estrogen receptor (ER) status is critical in determining endocrine therapy response and resistance mechanisms in breast cancer.
  • HER2 status influences response to specific endocrine agents like tamoxifen.
  • Further research is needed to understand and overcome acquired resistance to aromatase inhibitors.

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