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The immunomodulatory effects of endocrine therapy in breast cancer

Huanhuan Huang1,2, Jun Zhou3, Hailong Chen1

  • 1Department of Breast Surgery, Second Affiliated Hospital Zhejiang University, Zhejiang, 310009, Hangzhou, China.

Journal of Experimental & Clinical Cancer Research : CR
|January 8, 2021
PubMed

Insights

Selective estrogen receptor modulators (SERMs) and downregulators (SERDs) are standard endocrine therapies for ER-positive breast cancer. This review explores their immune-modulating effects and potential combination with immunotherapy.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Estrogen receptor (ER)-positive breast cancer is commonly treated with endocrine therapies like SERMs and SERDs.
  • Endocrine resistance remains a challenge, leading to the development of targeted therapies like PI3K-AKT-mTOR and CDK4/6 inhibitors.
  • The tumor immune microenvironment (TIM) significantly influences breast cancer progression and treatment outcomes.

Purpose of the Study:

  • To comprehensively review the immunomodulatory effects of endocrine therapies in breast cancer.
  • To explore the potential of combining endocrine therapy with immune checkpoint inhibitors.
  • To highlight the previously underappreciated role of TIM modulation in breast cancer treatment.

Main Methods:

  • Literature review of endocrine therapies, targeted small molecule inhibitors, and their impact on the tumor immune microenvironment.
  • Analysis of studies investigating the interplay between breast cancer, endocrine resistance, and immunotherapy.
  • Synthesis of current evidence on the immunomodulatory effects of therapeutic strategies.

Main Results:

  • Endocrine therapies, including SERMs and SERDs, exhibit significant immunomodulatory effects on the tumor microenvironment.
  • Targeted therapies (PI3K-AKT-mTOR, CDK4/6 inhibitors) used with anti-estrogen drugs can alter the immune landscape.
  • These combined strategies may enhance anti-tumor immunity, potentially improving treatment response.

Conclusions:

  • The immunomodulatory effects of endocrine therapy are critical for understanding treatment response and resistance.
  • Combining endocrine therapy with immune checkpoint inhibitors presents a promising strategy for ER-positive breast cancer.
  • Further research into TIM modulation is essential for optimizing breast cancer treatment paradigms.
Keywords:
Breast cancerCDK4/6Endocrine therapyPI3K-AKT-mTOR pathwayTumor immune microenvironment

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