Detection of high-risk patients resistant to CDK4/6 inhibitors with hormone receptor-positive HER2-negative advanced and metastatic breast cancer in Japan (KBCSG-TR-1316)
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Published:2023-07-24
Issue:6
Volume:30
Page:943-951
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ISSN:1340-6868
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Container-title:Breast Cancer
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language:en
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Short-container-title:Breast Cancer
Author:
Futamura ManabuORCID, Nakayama TakahiroORCID, Yoshinami Tetsuhiro, Oshiro Chiya, Ishihara MikiyaORCID, Morita MidoriORCID, Watanabe Akira, Tanigichi Azusa, Tsukabe Masami, Shimoda Masafumi, Nitta Kanae, Chihara Yoko, Yasojima Hiroyuki, Ouchi Yoshimi, Tokumaru YoshihisaORCID, Masuda NorikazuORCID
Abstract
Abstract
Background
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) improve the prognosis of hormone receptor-positive HER2-negative advanced/metastatic breast cancer (HR+/HER2− mBC). However, some cancers show resistance to CDK4/6i and have a poor prognosis. The non-luminal disease score (NOLUS) was developed to predict non-luminal disease using immunohistochemical analysis.
Methods
The association between the efficacy of CDK4/6i and NOLUS was investigated by evaluating pathological and clinical data, including real-world progression-free survival (rw-PFS) and overall survival (OS). Real-world data of patients with HR+/HER2− mBC who received CDK4/6i therapy [palbociclib or abemaciclib] as first- or second-line endocrine treatments was obtained. NOLUS was calculated using the formula: NOLUS (0–100) = − 0.45 × estrogen receptor (ER) (%) − 0.28 × progesterone receptor (PR) (%) + 0.27 × Ki67(%) + 73, and the patients were divided into two groups: NOLUS-positive (≥ 51.38) and NOLUS-negative (< 51.38).
Results
Of the 300 patients, 28 (9.3%) were NOLUS-positive, and 272 (90.7%) were NOLUS-negative. The expression rates (%) of ER and PgR in NOLUS-positive patients were lower than those in NOLUS-negative patients (p < 0.001). Ki67 expression was higher in NOLUS-positive patients. There were statistically significant differences in prognosis (rw-PFS and OS) between the two groups. Moreover, NOLUS-negative patients showed statistically better rw-PFS with first-line therapy than second-line therapy. However, NOLUS-positive patients showed poor prognoses with both the first and second therapeutic lines, suggesting CDK4/6i inefficacy for NOLUS-positive patients.
Conclusions
The efficacy and prognosis of CDK4/6i significantly differed between the NOLUS-positive and NOLUS-negative patients. This feasible method can predict patients with HR+/HER2− mBC resistant to CDK4/6i and help select a better therapeutic approach to overcome resistance.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Radiology, Nuclear Medicine and imaging,Oncology,General Medicine
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