The Predictive Role of Serum Lipid Levels, p53 and ki-67, According to Molecular Subtypes in Breast Cancer: A Randomized Clinical Study.

Andreea Clim, Ionut Flaviu Faur, Amadeus Dobrescu, Ioana Adelina Clim, Paul Pasca, Dan Brebu, Andreea-Adriana Neamtu, Ciprian Duta, Bogdan Totolici, Catalin Prodan-Barbulescu, Cristi Tarta, Carmen Neamtu, Mihai Rosu, Gabriel Lazar

Journal: International journal of molecular sciences 2024;25(7):

PMID: 38612725

Abstract

Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer. The number of studies on the predictive potential of the different components of the lipid profile with a predictive potential in breast cancer is quite low. The evaluation of the lipid profile was carried out for the 142 patients who benefited from neoadjuvant therapy (NAC) in order to identify a potential predictive biomarker. The serological sample collection was performed sequentially according to a standardized protocol, pre-NAC, post-NAC and 6 months post-NAC after a 6-h pre-collection fast. We also investigated in the general group the presence or absence of the p53 mutation (TP53) and of the mitotic index ki-67, respectively, in relation to the molecular subtypes. The menopausal status, tumor size, family history, grading, Ki-67, p53 and LN metastases have a predictive nature regarding overall survival (OS) ( < 0.05), while for disease free survival (DFS), only tumor size, tumor grading, Ki-67 > 14, and p53+ are of predictive nature. The genetic and molecular analysis carried out in our group indicates that 71.67% have a Ki-67 score higher than 14%, and 39% of the patients have the positive P53 mutation. The multivariate analysis in the case of patients included in the TNBC subtype showed that the increased tumor volume ( = 0.002) and increased level of HDL ( = 0.004) represent predictive factors for the tumor response rate to NAC. High HDL-C levels before NAC and increased LDL-C levels after NAC were associated with the better treatment response in ER-positive and HER2+ breast cancer patients. Increased HDL-C values and tumor volume represent predictive factors as to the response rate to NAC in the case of patients included in the TNBC subtype. Regarding the ER+ and HER2+ subtypes, increased levels of HDL-C pre-NAC and increased levels of LDL-C post-NAC were associated with a better therapeutic response rate. Tumor grading, Ki-67, p53, and LN metastases have a predictive nature for OS, while tumor size, tumor grading, and Ki-67 > 14, and p53+ are predictive for DFS.

Address: IInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, Romania.; X Department of General Surgery, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.; Multidisciplinary Doctoral School, "Vasile Goldiș" Western University of Arad, 310025 Arad, Romania.; IInd Surgery Clinic, Timisoara Emergency County Hospital, 300723 Timisoara, Romania.; X Department of General Surgery, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.; IInd Obstetrics and Gynecology Clinic "Dominic Stanca", 400124 Cluj-Napoca, Romania.; Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.; Department I-Discipline of Anatomy and Embryology, Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.; Faculty of Pharmacy, "Victor Babes" University of Medicine and Pharmacy Timisoara, Eftimie Murgu Sq., Nr. 2, 300041 Timișoara, Romania.; Pathology Department, Clinical County Emergency Hospital of Arad, Andrenyi Karoly Str, Nr. 2-4, 310037 Arad, Romania.; Ist Clinic of General Surgery, Arad County Emergency Clinical Hospital, 310158 Arad, Romania.; Department of General Surgery, Faculty of Medicine, "Vasile Goldiș" Western University of Arad, 310025 Arad, Romania.; Department of Morpho-Functional Sciences II, Discipline of Physiology, "Grigore T. Popa" University of Medicine and Pharmacy, 700115 Iasi, Romania.; Department of Oncology Surgery, "Iuliu Hatieganu" University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania.; Ist Clinic of Oncological Surgery, Oncological Institute "Prof. Dr. I Chiricuta", 400015 Cluj-Napoca, Romania.
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