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25-10-2023 | Breast Cancer | Clinical trial

Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer

Authors: Takayuki Iwamoto, Naoki Niikura, Kenichi Watanabe, Takashi Takeshita, Yuichiro Kikawa, Kokoro Kobayashi, Nobutaka Iwakuma, Takuho Okamura, Hiroshi Tada, Shinji Ozaki, Toshitaka Okuno, Uhi Toh, Yutaka Yamamoto, Michiko Tsuneizumi, Hiroshi Ishiguro, Norikazu Masuda, Shigehira Saji

Published in: Breast Cancer Research and Treatment | Issue 2/2024

Abstract

Purpose

Here, we investigated the potential predictive and elucidating efficacy of cell-free DNA (cfDNA) changes on clinical outcomes and biological effects, respectively, after short-term palbociclib and fulvestrant treatment for patients with hormone receptor (HR)-positive and human epidermal growth factor 2 (HER2)-negative advanced or metastatic breast cancer (ABC).

Methods

In this secondary analysis of the Japan Breast Cancer Research Group-M07 (FUTURE) trial, blood cfDNA was obtained before palbociclib treatment and on day 15 of cycle one (28-day cycle). Target enrichment was performed using next-generation sequencing; progression-free survival (PFS) was compared based on cfDNA changes between baseline and day 15 of cycle one after combination therapy.

Results

Fifty-six patients (112 paired blood samples) were examined. The median follow-up time was 8.9 months. PIK3CA (30.4%, 17/56), FOXA1 (30.4%, 17/56), and ESR1 (28.6%, 16/56) were most frequently mutated at baseline. The number of mutated genes was significantly decreased on day 15 compared with that at baseline (paired t test: P value = 0.025). No significant difference was observed in PFS (decrease group, 7.9 m vs the others, 9.3 m; log-rank P value = 0.75; hazard ratio, 1.13; 95% confidence interval, 0.53–2.41). Among patients without previous aromatase inhibitor treatment (n = 15), three (20%) had ESR1 mutations after progression to fulvestrant.

Conclusion

No significant association was observed between changes in mutated genes after short-term palbociclib and fulvestrant treatment and disease progression; a significant reduction in cfDNA mutation level was observed on day 15 of cycle one. Clinical meanings of cfDNA should be investigated in the future trials.

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Title: Changes in cell-free DNA after short-term palbociclib and fulvestrant treatment for advanced or metastatic hormone receptor-positive and human epidermal growth factor 2-negative breast cancer
Authors: Takayuki Iwamoto
Naoki Niikura
Kenichi Watanabe
Takashi Takeshita
Yuichiro Kikawa
Kokoro Kobayashi
Nobutaka Iwakuma
Takuho Okamura
Hiroshi Tada
Shinji Ozaki
Toshitaka Okuno
Uhi Toh
Yutaka Yamamoto
Michiko Tsuneizumi
Hiroshi Ishiguro
Norikazu Masuda
Shigehira Saji
Publication date: 25-10-2023
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Fulvestrant
Published in: Breast Cancer Research and Treatment / Issue 2/2024
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-023-07144-2

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