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)

doi:10.1007/s10549-024-07253-6

Review

. 2024 Jun;205(2):211-226.

doi: 10.1007/s10549-024-07253-6. Epub 2024 Feb 15.

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)

Lucy Gao^{1

2}, Arielle Medford^{1

2}, Laura Spring^{1

2}, Yael Bar¹, Bonnie Hu¹, Rachel Jimenez^{1

2}, Steven J Isakoff^{1

2}, Aditya Bardia^{1

2}, Jeffrey Peppercorn^{3

4}

Affiliations

¹ Massachusetts General Hospital, Boston, MA, USA.
² Harvard Medical School, Boston, MA, USA.
³ Massachusetts General Hospital, Boston, MA, USA. jpeppercorn@mgh.harvard.edu.
⁴ Harvard Medical School, Boston, MA, USA. jpeppercorn@mgh.harvard.edu.

PMID: 38355821
DOI: 10.1007/s10549-024-07253-6

Review

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)

Lucy Gao et al. Breast Cancer Res Treat. 2024 Jun.

. 2024 Jun;205(2):211-226.

doi: 10.1007/s10549-024-07253-6. Epub 2024 Feb 15.

Authors

Lucy Gao^{1

2}, Arielle Medford^{1

2}, Laura Spring^{1

2}, Yael Bar¹, Bonnie Hu¹, Rachel Jimenez^{1

2}, Steven J Isakoff^{1

2}, Aditya Bardia^{1

2}, Jeffrey Peppercorn^{3

4}

Affiliations

¹ Massachusetts General Hospital, Boston, MA, USA.
² Harvard Medical School, Boston, MA, USA.
³ Massachusetts General Hospital, Boston, MA, USA. jpeppercorn@mgh.harvard.edu.
⁴ Harvard Medical School, Boston, MA, USA. jpeppercorn@mgh.harvard.edu.

PMID: 38355821
DOI: 10.1007/s10549-024-07253-6

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.

Keywords: Biomarkers; Breast cancer; Circulating tumor DNA.

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References

1. Ahmad A (2019) Breast cancer statistics: recent trends. Adv Exp Med Biol 1152:1–7. https://doi.org/10.1007/978-3-030-20301-6_1 - DOI - PubMed
1. Pedersen RN, Esen BO, Mellemkjaer L, Christiansen P, Ejlertsen B, Lash TL, Norgaard M, Cronin-Fenton D (2022) The incidence of breast cancer recurrence 10–32 years after primary diagnosis. J Natl Cancer Inst 114:391–399. https://doi.org/10.1093/jnci/djab202 - DOI - PubMed
1. Tewari A, Chagpar AB (2014) Worry about breast cancer recurrence: a population-based analysis. Am Surg 80:640–645 - DOI - PubMed
1. Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM, Regan MM, Rimm DL, Symmans WF, Torlakovic EE, Varella L, Viale G, Weisberg TF, McShane LM, Wolff AC (2020) Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol 38:1346–1366. https://doi.org/10.1200/JCO.19.02309 - DOI - PubMed
1. Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JM, Bilous M, Ellis IO, Fitzgibbons P, Hanna W (2018) Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update. Arch Pathol Lab Med 142:1364–1382 - DOI - PubMed

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[1] Ahmad A (2019) Breast cancer statistics: recent trends. Adv Exp Med Biol 1152:1–7. https://doi.org/10.1007/978-3-030-20301-6_1 - DOI - PubMed

[2] Ahmad A (2019) Breast cancer statistics: recent trends. Adv Exp Med Biol 1152:1–7. https://doi.org/10.1007/978-3-030-20301-6_1 - DOI - PubMed

[3] Pedersen RN, Esen BO, Mellemkjaer L, Christiansen P, Ejlertsen B, Lash TL, Norgaard M, Cronin-Fenton D (2022) The incidence of breast cancer recurrence 10–32 years after primary diagnosis. J Natl Cancer Inst 114:391–399. https://doi.org/10.1093/jnci/djab202 - DOI - PubMed

[4] Pedersen RN, Esen BO, Mellemkjaer L, Christiansen P, Ejlertsen B, Lash TL, Norgaard M, Cronin-Fenton D (2022) The incidence of breast cancer recurrence 10–32 years after primary diagnosis. J Natl Cancer Inst 114:391–399. https://doi.org/10.1093/jnci/djab202 - DOI - PubMed

[5] Tewari A, Chagpar AB (2014) Worry about breast cancer recurrence: a population-based analysis. Am Surg 80:640–645 - DOI - PubMed

[6] Tewari A, Chagpar AB (2014) Worry about breast cancer recurrence: a population-based analysis. Am Surg 80:640–645 - DOI - PubMed

[7] Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM, Regan MM, Rimm DL, Symmans WF, Torlakovic EE, Varella L, Viale G, Weisberg TF, McShane LM, Wolff AC (2020) Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol 38:1346–1366. https://doi.org/10.1200/JCO.19.02309 - DOI - PubMed

[8] Allison KH, Hammond MEH, Dowsett M, McKernin SE, Carey LA, Fitzgibbons PL, Hayes DF, Lakhani SR, Chavez-MacGregor M, Perlmutter J, Perou CM, Regan MM, Rimm DL, Symmans WF, Torlakovic EE, Varella L, Viale G, Weisberg TF, McShane LM, Wolff AC (2020) Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol 38:1346–1366. https://doi.org/10.1200/JCO.19.02309 - DOI - PubMed

[9] Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JM, Bilous M, Ellis IO, Fitzgibbons P, Hanna W (2018) Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update. Arch Pathol Lab Med 142:1364–1382 - DOI - PubMed

[10] Wolff AC, Hammond MEH, Allison KH, Harvey BE, Mangu PB, Bartlett JM, Bilous M, Ellis IO, Fitzgibbons P, Hanna W (2018) Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update. Arch Pathol Lab Med 142:1364–1382 - DOI - PubMed

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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)

Affiliations

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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