1. 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).
- Author
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Futamura M, Nakayama T, Yoshinami T, Oshiro C, Ishihara M, Morita M, Watanabe A, Tanigichi A, Tsukabe M, Shimoda M, Nitta K, Chihara Y, Yasojima H, Ouchi Y, Tokumaru Y, and Masuda N
- Subjects
- Humans, Female, Japan, Ki-67 Antigen, Progression-Free Survival, Receptors, Estrogen, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Receptor, ErbB-2, Breast Neoplasms drug therapy
- 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., (© 2023. The Author(s).)
- Published
- 2023
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