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Diffuse optical tomography breast imaging measurements are modifiable with pre-surgical targeted and endocrine therapies among women with early stage breast cancer

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Abstract

Purpose

Diffuse optical tomography breast imaging system (DOTBIS) non-invasively measures tissue concentration of hemoglobin, which is a potential biomarker of short-term response to neoadjuvant chemotherapy. We evaluated whether DOTBIS-derived measurements are modifiable with targeted therapies, including AKT inhibition and endocrine therapy.

Methods

We conducted a proof of principle study in seven postmenopausal women with stage I-III breast cancer who were enrolled in pre-surgical studies of the AKT inhibitor MK-2206 (n = 4) or the aromatase inhibitors exemestane (n = 2) and letrozole (n = 1). We performed DOTBIS at baseline (before initiation of therapy) and post-therapy in the affected breast (tumor volume) and contralateral, unaffected breast, and measured tissue concentrations (in μM) of total hemoglobin (ctTHb), oxyhemoglobin (ctO2Hb), and deoxyhemoglobin (ctHHb), as well as water fraction (%).

Results

We found consistent decreases in DOTBIS-measured hemoglobin concentrations in tumor volume, with median percent changes for ctTHb, ctHHb, ctO2Hb, and water fraction for the entire cohort of − 27.1% (interquartile range [IQR] 37.5%), − 49.8% (IQR 29.3%), − 33.5% (IQR 47.4%), and − 3.6% (IQR 10.6%), respectively. In the contralateral breast, median percent changes for ctTHb, ctHHb, ctO2Hb, and water fraction were + 1.8% (IQR 26.7%), − 8.6% (IQR 29.3%), + 6.2% (IQR 29.5%), and + 1.9% (IQR 30.7%), respectively.

Conclusion

We demonstrated that DOTBIS-derived measurements are modifiable with pre-surgical AKT inhibition and endocrine therapy, supporting further investigation of DOTBIS as a potential imaging assessment of response to neoadjuvant targeted therapies in early stage breast cancer.

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Fig. 1
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Data availability

Supporting data can be made available upon written request for non-commercial purposes to researchers subject to a non-disclosure agreement with all relevant parties, and by contacting the corresponding author.

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Acknowledgements

The authors wish to thank the study participants and the principal investigator (PIs) of the FELINE and pre-surgical exemestane trials, Drs. Qamar Khan, MD, and Bernardo Bonanni, MD, respectively.

Funding

This work was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant Number UL1TR001873. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Author information

Authors and Affiliations

  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

    Julia E. McGuinness, Meghna S. Trivedi, Melissa K. Accordino, Katherine D. Crew & Dawn L. Hershman

  2. Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA

    Julia E. McGuinness, Mariella Tejada, Meghna S. Trivedi, Melissa K. Accordino, Katherine D. Crew & Dawn L. Hershman

  3. Department of Biomedical Engineering, New York University Tandon School of Engineering, Brooklyn, NY, USA

    Mirella L. Altoe, Alessandro Marone & Andreas H. Hielscher

  4. Department of Biostatistics, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA

    Lauren E. Franks & Shing M. Lee

  5. Department of Radiology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA

    Hyun K. Kim

  6. Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY, USA

    Katherine D. Crew & Dawn L. Hershman

  7. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Kevin Kalinsky

Authors
  1. Julia E. McGuinness
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  2. Mirella L. Altoe
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  3. Alessandro Marone
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  4. Lauren E. Franks
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  5. Shing M. Lee
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  6. Hyun K. Kim
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  7. Mariella Tejada
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  9. Melissa K. Accordino
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  10. Katherine D. Crew
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  11. Dawn L. Hershman
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  12. Andreas H. Hielscher
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  13. Kevin Kalinsky
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Contributions

All authors contributed to the design of this work, analysis and interpretation of data, and writing of the manuscript. All authors have approved the completed version of the manuscript and are accountable for all aspects of the work.

Corresponding author

Correspondence to Julia E. McGuinness.

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Conflict of interest

JEM, MLA, AM, LEF, SL, HKK, MT, MST, MKA, KDC, DLH, AHH declare no conflict of interest. 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.

Ethical approval

The institutional review board at Columbia University Irving Medical Center approved the study protocol (AAAI9154).

Informed consent

Informed consent was obtained from all patients prior to their enrollment.

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McGuinness, J.E., Altoe, M.L., Marone, A. et al. Diffuse optical tomography breast imaging measurements are modifiable with pre-surgical targeted and endocrine therapies among women with early stage breast cancer. Breast Cancer Res Treat 189, 297–304 (2021). https://doi.org/10.1007/s10549-021-06320-6

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  • DOI: https://doi.org/10.1007/s10549-021-06320-6

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