Pharmacogenetics of response to neoadjuvant paclitaxel treatment for locally advanced breast cancer

Abstract

Locally advanced breast cancer (LABC) cases have a varying five-year survival rate, mainly influenced by the tumor response to chemotherapy. Paclitaxel activity (response rate) varies across populations from 21.5% to 84%. There are some reports on genetic traits and paclitaxel; however, there is still considerable residual unexplained variability. In this study, we aimed to test the association between eleven novel markers and tumor response to paclitaxel and to explore if any of them influenced tumor protein expression. We studied a cohort of 140 women with LABC. At baseline, we collected a blood sample (for genotyping), fine needle aspirates (for Western blot), and tumor measurements by imaging. After follow-up, we ascertained the response to paclitaxel monotherapy by comparing the percent change in the pre-, post- tumor measurements after treatment. To allocate exposure, we genotyped eleven SNPs with TaqMan probes on RT-PCR and regressed them to tumor response using linear modeling. In addition, we compared protein expression, between breast tumors and healthy controls, of those genes whose genetic markers were significantly associated with tumor response. After adjusting for multiple clinical covariates, SNPs on the LPHN2, ROBO1, SNTG1, and GRIK1 genes were significant independent predictors of poor tumor response (tumor growth) despite paclitaxel treatment. Moreover, proteins encoded by those genes are significantly downregulated in breast tumor samples.

Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma

“…Intronic SNPs of LPHN2 have been reported to be associated with decreased paclitaxel sensitivity in cancer cell lines, and the authors proposed that microtubule interactions of LPHN2 could play an important role in paclitaxel response [ 21 ]. In another study involving advanced breast cancer, a SNP of LPHN2 was significantly related to poor tumor response [ 22 ]. CRHR1 encodes a receptor that binds neuropeptides of the corticotropin-releasing hormone family.…”

Delving into the significance of the His289Tyr single-nucleotide polymorphism in the glutamate ionotropic receptor kainate-1 (Grik1) gene of a genetically audiogenic seizure model

“…In this study, we adhered to the manufacturer's guidelines and utilized this primary antibody for both Western blotting and immunocytochemistry. This primary antibody has been utilized successfully in prior immunohistochemical studies conducted by our research group (Díaz-Rodríguez et al, 2023) and by others (Perez-Ortiz et al, 2017). Nevertheless, as per the manufacturer's data sheets, hamster brain tissue reactivity remains untested.…”

Quantitative Proteomics of Breast Benign and Malignant Tumors Reveals a Malignancy Signature

“…Patients identi ed as HER2/neu positive (IHC 3+) additionally received trastuzumab with a loading dose of 8 mg/kg and maintenance dose of 6 mg/kg. These samples are sourced from a prior study investigation conducted by Perez-Ortiz et al 15 at the North Zone General Hospital SSEP, Puebla, Pue., Mexico and National Cancer Institute in Mexico City (INCAN). All tissue specimens were obtained through breast-conserving surgery (tumorectomy) after chemotherapy completion and subsequently samples were preserved at -70°C (Fig.…”