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Open Access 05-01-2024 | Tamoxifen | Preclinical study

Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma

Authors: Saki Nakagawa, Minoru Miyashita, Ichiro Maeda, Atsushi Goda, Hiroshi Tada, Masakazu Amari, Yasuyuki Kojima, Koichiro Tsugawa, Yasuyo Ohi, Yasuaki Sagara, Miku Sato, Akiko Ebata, Narumi Harada-Shoji, Takashi Suzuki, Makoto Nakanishi, Tomohiko Ohta, Takanori Ishida

Published in: Breast Cancer Research and Treatment | Issue 3/2024

Abstract

Background

Invasive lobular carcinoma (ILC) is distinct from invasive ductal carcinoma (IDC) in terms of their hormonal microenvironments that may require different therapeutic strategies. We previously reported that selective estrogen receptor modulator (SERM) function requires F-box protein 22 (Fbxo22). Here, we investigated the role of Fbxo22 as a potential biomarker contributing to the resistance to endocrine therapy in ILC.

Methods

A total of 302 breast cancer (BC) patients including 150 ILC were recruited in the study. Fbxo22 expression and clinical information were analyzed to elucidate whether Fbxo22 negativity could be a prognostic factor or there were any correlations among clinical variables and SERM efficacy.

Results

Fbxo22 negativity was significantly higher in ILC compared with IDC (58.0% vs. 27.0%, P < 0.001) and higher in postmenopausal patients than premenopausal patients (64.1% vs. 48.2%, P = 0.041). In the ILC cohort, Fbxo22-negative patients had poorer overall survival (OS) than Fbxo22-positive patients, with 10-year OS rates of 77.4% vs. 93.6% (P = 0.055). All patients treated with SERMs, Fbxo22 negativity resulted in a poorer outcome, with 10-year OS rates of 81.3% vs. 92.3% (P = 0.032). In multivariate analysis regarding recurrence-free survival (RFS) in ILC patients, Fbxo22 status was independently predictive of survival as well as lymph node metastasis.

Conclusion

Fbxo22 negativity significantly impacts on survival in BC patients with IDC and ILC, and the disadvantage was enhanced among ILC postmenopausal women or patients treated with SERMs. The findings suggest that different therapeutic strategies might be needed according to the different histopathological types when considering adjuvant endocrine therapy.

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Title: Potential role of Fbxo22 in resistance to endocrine therapy in breast cancer with invasive lobular carcinoma
Authors: Saki Nakagawa
Minoru Miyashita
Ichiro Maeda
Atsushi Goda
Hiroshi Tada
Masakazu Amari
Yasuyuki Kojima
Koichiro Tsugawa
Yasuyo Ohi
Yasuaki Sagara
Miku Sato
Akiko Ebata
Narumi Harada-Shoji
Takashi Suzuki
Makoto Nakanishi
Tomohiko Ohta
Takanori Ishida
Publication date: 05-01-2024
Publisher: Springer US
Keywords: Tamoxifen
Breast Cancer
Breast Cancer
Selective Estrogen Receptor Modulator
Published in: Breast Cancer Research and Treatment / Issue 3/2024
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-023-07209-2

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Abstract

Background

Methods

Results

Conclusion

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