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Phase II study of propranolol feasibility with neoadjuvant chemotherapy in patients with newly diagnosed breast cancer

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Abstract

Purpose

Propranolol regulates angiogenesis in pre-clinical models and reduces distant breast cancer (BC) metastases in observational studies. We assessed the feasibility of combining propranolol with neoadjuvant chemotherapy (NAC) in patients with BC.

Methods

Women with clinical stage II–III BC undergoing NAC [weekly paclitaxel × 12, followed by dose-dense adriamycin/cyclophosphamide (AC) × 4] started propranolol 20 mg PO BID with paclitaxel #1, and increased to 80 mg extended release (ER) PO daily, as tolerated. The primary endpoint was to assess feasibility, defined as at least 75% of patients having at least 80% adherence to propranolol as prescribed. Secondary endpoints included identifying safety, rate of dose holds and modification, and rate of reaching 80 mg ER daily. The proposed sample size was 20 patients.

Results

From November 2012 to September 2015, ten patients were enrolled. Median age was 50.5 years (range, 44–67). All patients had hormone receptor-positive/HER2-negative breast cancer. Three women had grade I bradycardia that resulted in a 1-week delay in increasing the propranolol dose. Ninety percent of women reached the target propranolol dosing of 80 mg ER daily, and 70% took the target propranolol dose until the night before surgery. Of the 4 women who dose-reduced propranolol, 1 increased to the target propranolol dose. Mean adherence to propranolol dosing was 96% (range: 91–100%). All patients went to surgery.

Conclusion

Our results support the feasibility of combining propranolol (up to 80 mg ER) with neoadjuvant taxane/anthracycline-based chemotherapy.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

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Funding

No funding to report.

Author information

Authors and Affiliations

  1. Columbia University Irving Medical Center, 630 W 168th St, New York, NY, 10032, USA

    Madeleine B. Hopson, Melissa Accordino, Meghna Trivedi, Katherine D. Crew & Dawn L. Hershman

  2. Mailman School of Public Health, Columbia University, 722 W 168th St, New York, NY, 10032, USA

    Shing Lee, Katherine D. Crew & Dawn L. Hershman

  3. Herbert Irving Comprehensive Cancer Center, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA

    Shing Lee, Melissa Accordino, Meghna Trivedi, Katherine D. Crew & Dawn L. Hershman

  4. Bristol-Myers Squibb, 100 Nassau Park Blvd #300, Princeton, NJ, 08540, USA

    Matthew Maurer

  5. Winship Cancer Institute at Emory University, 1365 Clifton Road, Suite B4112, Atlanta, GA, 30322, USA

    Kevin Kalinsky

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  1. Madeleine B. Hopson
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  2. Shing Lee
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Contributions

All authors contributed to the study conception and design. Material preparation and analysis were performed by MBH, SL, and KK. The first draft of the manuscript was written by MBH and KK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kevin Kalinsky.

Ethics declarations

Conflict of interest

MBH owns stock in Viking Therapeutics, Karyopharm Therapeutics, Regeneron, Eli Lilly, and Amgen. MM is employed by Bristol-Myers Squibb. KK has served an advisory/consulting role for Eli Lilly, Pfizer, Novartis, Eisai, AstraZeneca, Immunomedics, Merck, Seattle Genetics, and Cyclocel, owns stock in Grail, Array BioPharma, and Pfizer, and his spouse was previously employed by Array Biopharma and Pfizer.

Ethical approval

This study was approved by the Columbia University Irving Medical Center Institutional Review Board.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

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Not applicable.

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Hopson, M.B., Lee, S., Accordino, M. et al. Phase II study of propranolol feasibility with neoadjuvant chemotherapy in patients with newly diagnosed breast cancer. Breast Cancer Res Treat 188, 427–432 (2021). https://doi.org/10.1007/s10549-021-06210-x

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  • DOI: https://doi.org/10.1007/s10549-021-06210-x

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