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Clinical trial data and emerging immunotherapeutic strategies: hormone receptor-positive, HER2− negative breast cancer

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Abstract

While checkpoint inhibitors have been approved in patients with newly metastatic PDL1-positive triple negative breast cancer, similar clinical benefit with immunotherapy alone or in combination with chemotherapy has not been observed in patients with hormone receptor-positive, HER2− negative breast cancer in the metastatic setting. However, in the ISPY2 trial, an increase in pathologic response has been observed with the addition of immunotherapy (± PARP inhibition) to chemotherapy compared to chemotherapy alone in patients with high-risk hormone receptor-positive, HER2− breast cancer. We review strategies to enhance the immunotherapeutic activity in this subtype of breast cancer, including combinations of checkpoint inhibition with chemotherapy, endocrine therapy, PARP inhibitors, HDAC inhibitors, CDK4/6 inhibitors, and radiotherapy. Combinations with agents targeting novel immunotherapeutic targets are also discussed. Though there remains an unmet need for immunotherapy approaches in patients with hormone-receptor positive breast cancer, there are a number of approaches that may lead to increased anti-tumor activity with immunotherapy in this tumor subtype.

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  1. Matthew R. Kearney and Julia E. McGuinness are co-first authors

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  1. Division of Hematology and Medical Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA

    Matthew R. Kearney & Julia E. McGuinness

  2. Division of Hematology & Oncology, Department of Hematology and Medical Oncology, Glenn Family Breast Center, Winship Cancer Institute, Emory University, 1365 Clifton Road, NE, Atlanta, GA, 30322, USA

    Kevin Kalinsky

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All authors (MK, JEM, KK) contributed equally to this manuscript.

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MK and JEM have no disclosures to report. KK declares the following potential conflicts of interest: Medical Advisor—Immunomedics, Pfizer, Novartis, Eisai, Eli-Lilly, Amgen, Immunomedics, Merck, Seattle Genetics, and Astra Zeneca; Institutional Support—Immunomedics, Novartis, Incyte, Genentech/Roche, Eli-Lilly, Pfizer, Calithera Biosciences, Acetylon, Seattle Genetics, Amgen, Zentalis Pharmaceuticals, and CytomX Therapeutics; Speakers Bureau—Eli-Lilly; Spouse—Array Biopharma, Pfizer, Grail.

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Kearney, M.R., McGuinness, J.E. & Kalinsky, K. Clinical trial data and emerging immunotherapeutic strategies: hormone receptor-positive, HER2− negative breast cancer. Breast Cancer Res Treat 189, 1–13 (2021). https://doi.org/10.1007/s10549-021-06291-8

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