Abstract
Background
Clinical and genomic data from patients with early-stage breast cancer suggest more aggressive disease in premenopausal women. However, the association between age, disease course, and molecular profile from liquid biopsy in metastatic breast cancer (MBC) is not well characterized.
Methods
Patients were classified as premenopausal (< 45 years), perimenopausal (45–55 years), or postmenopausal (> 55 years). Cohort 1 consisted of patients with MBC who consented for prospective serial evaluation of circulating tumor cells (CTCs) using CellSearch™. Cohort 2 included patients who, as part of routine care, had circulating tumor DNA (ctDNA) sequenced by the Guardant360™ assay. Clinicopathologic data were collected from retrospective review to compare disease features between premenopausal and postmenopausal women.
Results
Premenopausal women represented 26% of 138 patients in Cohort 1 and 21% of 253 patients in Cohort 2. In Cohort 1, younger patients had a shorter time to metastases and a higher prevalence of lung and brain metastases. Overall, there were similar rates of ≥ 5 CTCs/7.5 mL, HER2 + CTC expression, and CTC clusters between pre- and postmenopausal women. However, for those with triple negative breast cancer, premenopausal women had a higher proportion of ≥ 5 CTCs/7.5 mL. In Cohort 2, premenopausal women had a higher incidence of FGFR1 (OR 2.75, p = 0.022) and CCND2 (OR 6.91, p = 0.024) alterations. There was no difference in the ctDNA mutant allele frequency or the number of detected alterations between these age groups.
Conclusions
Our data reveal that premenopausal women diagnosed with MBC have unique clinical, pathologic, and molecular features when compared to their postmenopausal counterparts. Our results highlight FGFR1 inhibitors as potential therapeutics of particular interest among premenopausal women.
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Data availability
The datasets generated and/or analyzed during the current study are not publicly available due ongoing data collection but are available from the corresponding author on reasonable request.
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Lynn Sage Research Foundation.
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ANS, KC, LG, and MC involved in concept/design of work; ANS, KC, LG, AAD, QZ, and SJ collected the data; ANS, KC, and LG performed data analysis/interpretation; ANS and KC wrote the manuscript; and all involved in critical revision of the article and final approval of the version to be published.
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Ami N. Shah: Honorarium—Taiho, Daiichi-Sankyo, Pfizer; Advisory Board—d AbbVie; Lorenzo Gerratana: Advisory board—Lilly; Amir Behdad: Fees for Non-CME Services Received Directly from Commercial Interest or their Agents (e.g., speakers' bureaus); Author; Pfizer, Bayer, Foundation Medicine; Massimo Cristofanilli: Advisory Board—G1 Therapeutics, Cytodyn, Sermonix, LIlly, Foundation Medicine. Fees for Non-CME Services Received Directly from Commercial Interest or their Agents—Pfizer. Contracted Research—G1 Therapeutics. Others: none.
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This protocol was approved by the institutional review board at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University (STU00203283 and STU00214133).
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Patients provided written consent to participate in part 1.
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Requirement for informed consent was waived for part 2 for this retrospective review of de-identified patient data.
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Shah, A.N., Carroll, K.J., Gerratana, L. et al. Circulating tumor cells, circulating tumor DNA, and disease characteristics in young women with metastatic breast cancer. Breast Cancer Res Treat 187, 397–405 (2021). https://doi.org/10.1007/s10549-021-06236-1
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DOI: https://doi.org/10.1007/s10549-021-06236-1