The impact of vitamin D levels on the progression-free survival of women with hormone receptor-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors.

person Alejandro Aranda-Gutierrez Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico info_outline Alejandro Aranda-Gutierrez, Andres Meraz-Brenez, Hector Raul Gonzalez-Sanchez, Haydee Cristina Verduzco-Aguirre, Bertha Alejandra Martinez-Cannon

Authors person Alejandro Aranda-Gutierrez Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico info_outline Alejandro Aranda-Gutierrez, Andres Meraz-Brenez, Hector Raul Gonzalez-Sanchez, Haydee Cristina Verduzco-Aguirre, Bertha Alejandra Martinez-Cannon Organizations Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico Abstract Disclosures Research Funding No funding sources reported Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) halt the transition from the G1 to the S phase, a process governed by the hyperphosphorylation of the retinoblastoma (Rb) protein. Similarly, vitamin D3 has been demonstrated to induce cell cycle arrest through the inhibition of various cyclin-dependent kinases, including those responsible for phosphorylating the Rb protein. Therefore, we hypothesized that suboptimal vitamin D levels may compromise the efficacy of CDK4/6i used to treat hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). Methods: We conducted a retrospective single-center study of women diagnosed with HR-positive, HER2-negative MBC and treated with any CDK4/6i between 2020 and 2023. Eligible patients were those who received at least one cycle of CDK4/6i, had a baseline 25-OH vitamin D measurement, and had a follow-up period of more than three months. Independent samples T-test, X2, and Fisher’s exact tests were used to evaluate associations between variables. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and compared according to vitamin D levels using the log-rank test. Results: Among 31 patients, the mean age at diagnosis was 53 years (SD 14), 24 (77%) received CDK4/6i in the first-line setting, and 9 (29%) had suboptimal vitamin D levels (<20 ng/ml). Clinicopathological features based on vitamin D levels are shown (Table). The type of iCDK was different according to vitamin D levels (p = 0.036), with no other observed differences between groups. With a median follow-up of 26 months (95% CI 17-35) since iCDK initiation, median PFS was not reached for the entire cohort. A univariate analysis revealed that patients with suboptimal vitamin D levels had an inferior median PFS compared to patients with optimal levels (14 months [95%CI 4-24] vs. not reached [p=0.016]). Notably, no other parameter was associated with PFS in univariate analyses. Conclusions: In this cohort of Mexican patients with HR-positive, HER2-negativeMBC, suboptimal vitamin D levels adversely impacted PFS. Given the retrospective nature of this study and the limited number of patients, we emphasize the importance of studying these findings prospectively. Vitamin D Levels Optimal (>=20 ng/ml) Suboptimal (<20 ng/ml) p- value n 22 (71%) 9 (29%) Age (mean + SD) 55 + 13 48 + 14 0.143 Menopausal status Premenopausal Postmenopausal 8 (36%) 14 (64%) 6 (67%) 3 (33%) 0.124 Disease presentation Recurrent De novo 14 (64%) 8 (36%) 6 (67%) 3 (33%) 0.873 # of metastatic sites 1 >=2 4 (18%) 18 (82%) 1 (11%) 8 (89%) 0.627 Type of metastasis Non-visceral Visceral 12 (55%) 10 (45%) 3 (33%) 6 (67%) 0.283 iCDK4/6 treatment line First Second 18 (82%) 4 (18%) 6 (67%) 3 (33%) 0.360 Specific iCDK4/6 used Palbociclib Ribociclib Abemaciclib 14 (64%) 8 (36%) 0 9 (100%) 0 0 0.036