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Mutation profile differences in younger and older patients with advanced breast cancer using circulating tumor DNA (ctDNA)

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Abstract

Purpose

Little is known regarding the mutation profiles of ctDNA in the older adult breast cancer population. The objective of this study is to assess differences in mutation profiles in the older adult breast cancer population using a ctDNA assay as well as assess utilization of testing results.

Methods

Patients with advanced breast cancer underwent molecular profiling using a plasma-based ctDNA NGS assay (Guardant360) between 5/2015 and 10/2019 at Siteman Cancer Center. The profiling results of a multi-institutional database of patients with advanced breast cancer who had undergone molecular profiling were obtained. Associations between mutations and age group (≥ 65 vs. < 65) were examined using a Fisher’s exact test.

Results

In the single-institutional cohort, 148 patients (69.2%) were < 65 years old and 66 patients (30.8%) ≥ 65 years old. ATM, BRAF, and PIK3CA mutations were found more frequently in older patients with ER + HER2- breast cancers (p < 0.01). In the multi-institutional cohort, 5367 (61.1%) were < 65 years old and 3417 (38.9%) ≥ 65 years old. ATM, PIK3CA, and TP53 mutations were more common in the older cohort (p < 0.0001) and MYC and GATA3 mutations were less common in the older cohort (p < 0.0001). CtDNA testing influenced next-line treatment management in 40 (19.8%) patients in the single-institutional cohort.

Conclusion

When controlling for subtype, results from a single institution were similar to the multi-institutional cohort showing that ATM and PIK3CA were more common in older adults. These data suggest there may be additional molecular differences in older adults with advanced breast cancers.

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Funding

We would like to acknowledge research funding support from the St. Louis Men's Group Against Cancer.

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Authors and Affiliations

  1. Washington University, 660 South Euclid Avenue, Campus Box 8056, Saint Louis, MO, 63110, USA

    Katherine Clifton, Jingqin Luo, Yu Tao, Anna Roshal, Ashley Frith, Caron Rigden, Foluso Ademuyiwa, Katherine Weilbaecher, Leonel Hernandez-Aya, Lindsay L. Peterson, Nusayba Bagegni, Rama Suresh, Ron Bose, Mateusz Opyrchal, Tanya M. Wildes & Cynthia Ma

  2. Guardant Health, Redwood City, CA, USA

    Jennifer Saam & Thereasa Rich

Authors
  1. Katherine Clifton
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  2. Jingqin Luo
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Corresponding author

Correspondence to Katherine Clifton.

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Conflict of interest

Jennifer Saam and Thereasa Rich are employees of Guardant Health and own stock in Guardant Health.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

IRB approval was obtained for this study and a waiver of informed consent was obtained due to the retrospective nature of the study.

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Clifton, K., Luo, J., Tao, Y. et al. Mutation profile differences in younger and older patients with advanced breast cancer using circulating tumor DNA (ctDNA). Breast Cancer Res Treat 185, 639–646 (2021). https://doi.org/10.1007/s10549-020-06019-0

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  • DOI: https://doi.org/10.1007/s10549-020-06019-0

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