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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)

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 devel...

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Detalles Bibliográficos
Autores principales: Futamura, Manabu, Nakayama, Takahiro, Yoshinami, Tetsuhiro, Oshiro, Chiya, Ishihara, Mikiya, Morita, Midori, Watanabe, Akira, Tanigichi, Azusa, Tsukabe, Masami, Shimoda, Masafumi, Nitta, Kanae, Chihara, Yoko, Yasojima, Hiroyuki, Ouchi, Yoshimi, Tokumaru, Yoshihisa, Masuda, Norikazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Nature Singapore 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587336/
https://www.ncbi.nlm.nih.gov/pubmed/37486454
http://dx.doi.org/10.1007/s12282-023-01485-y
Descripción
Sumario: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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12282-023-01485-y.