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Searching for the “Holy Grail” of breast cancer recurrence risk: a narrative review of the hunt for a better biomarker and the promise of circulating tumor DNA (ctDNA)

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Abstract

Background

This paper is a narrative review of a major clinical challenge at the heart of breast cancer care: determining which patients are at risk of recurrence, which require systemic therapy, and which remain at risk in the survivorship phase of care despite initial therapy.

Methods

We review the literature on prognostic and predictive biomarkers in breast cancer with a focus on detection of minimal residual disease.

Results

While we have many tools to estimate and refine risk that are used to individualize local and systemic therapy, we know that we continue to over treat many patients and undertreat others. Many patients also experience what is, at least in hindsight, needless fear of recurrence. In this review, we frame this dilemma for the practicing breast oncologist and discuss the search for what we term the “holy grail” of breast cancer evaluation: the ideal biomarker of residual distant disease. We review the history of attempts to address this problem and the up-to-date science on biomarkers, circulating tumor cells and circulating tumor DNA (ctDNA).

Conclusion

This review suggests that the emerging promise of ctDNA may help resolve a crticical dilemma at the heart of breast cancer care, and improve prognostication, treatment selection, and outcomes for patients with breast cancer.

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Authors and Affiliations

  1. Massachusetts General Hospital, Boston, MA, USA

    Lucy Gao, Arielle Medford, Laura Spring, Yael Bar, Bonnie Hu, Rachel Jimenez, Steven J. Isakoff, Aditya Bardia & Jeffrey Peppercorn

  2. Harvard Medical School, Boston, MA, USA

    Lucy Gao, Arielle Medford, Laura Spring, Rachel Jimenez, Steven J. Isakoff, Aditya Bardia & Jeffrey Peppercorn

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The following authors declare financial relationships, none directly related to the work submitted: Jeffrey Peppercorn reports a family member employed by GSK. Arielle Medford has consulted for Guardant Health, Illumina, and Natera. Laura Spring has received research funding from Merck, Phillips, and Eli Lilly, and has consulted for Novartis and Puma. Steven J Isakoff has received research funding from Abbvie, Astra Zeneca, Genentech, Merck, and OncoPep, and has consulted for Seattle Genetics, Novartis, Paxman, and Puma, and reports a family member employed by Merus NV. Aditya Bardia has consulted for Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Sanofi, Daiichi Pharma/Astra Zeneca, Phillips, Eli Lilly, Foundation Medicine and he reports research funding from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/Astra Zeneca, and Eli Lilly.

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Gao, L., Medford, A., Spring, L. et al. Searching for the “Holy Grail” of breast cancer recurrence risk: a narrative review of the hunt for a better biomarker and the promise of circulating tumor DNA (ctDNA). Breast Cancer Res Treat 205, 211–226 (2024). https://doi.org/10.1007/s10549-024-07253-6

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