Hormonal Receptor Variability in Breast Cancer Metastasis

Breast cancer metastasis often exhibits marked heterogeneity in the expression of key hormonal receptors, notably oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This variability arises through clonal evolution, selective pressure of systemic therapies and influences of the tumour microenvironment. Receptor conversion—loss or gain of receptor expression between primary tumours and metastatic sites—affects up to one third of patients and can alter intrinsic molecular subtypes. Such shifts carry profound clinical consequences: loss of ER or PR may confer resistance to endocrine therapies, while de novo or acquired HER2 positivity can open avenues for targeted agents. The frequency and patterns of conversion vary according to the metastatic organ, prior treatments and biological subtype of the primary tumour. Routine reassessment of receptor status in metastatic lesions is therefore essential to inform therapeutic decisions, optimise patient outcomes and guide the development of novel strategies to overcome endocrine resistance and target microenvironment-driven subtype evolution.

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Hormonal Receptor Variability in Breast Cancer Metastasis publication trend

The graph below shows the total number of articles in hormonal receptor variability in breast cancer metastasis across all publications each year (not limited to Nature Index journals).

Technical terms

Estrogen receptor (ER): nuclear hormone receptor that binds oestrogen to regulate gene transcription and drive proliferation in breast epithelial cells.

Progesterone receptor (PR): nuclear receptor activated by progesterone, modulating cellular differentiation and response to endocrine therapy.

HER2 (ErbB2): receptor tyrosine kinase whose overexpression or amplification promotes tumour growth and serves as a target for monoclonal antibodies and kinase inhibitors.

Receptor conversion: change in hormone receptor or HER2 status between a primary tumour and its metastatic lesions, often influencing subtype classification and treatment choice.

Tumour microenvironment (TME): the surrounding cellular and acellular milieu in which cancer cells reside, including immune cells, stromal elements and extracellular matrix, which can drive receptor variability and therapy resistance.

References

1. Receptor conversion and survival in breast cancer liver metastases. Breast Cancer Research (2023).
2. Macrophages Promote Subtype Conversion and Endocrine Resistance in Breast Cancer. Cancers (2024).
3. Discordance of Biomarker Expression Profile between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis in Preoperative Core Needle Biopsy. Diagnostics (2024).