taxane and Musculoskeletal-Diseases

Women with breast cancer treated with aromatase inhibitors (AIs) may experience musculoskeletal symptoms that lead to discontinuation of effective therapy. The purpose of the current study is to evaluate the clinical and genetic predictors for AIs-related musculoskeletal adverse events(MS-AEs).. We recruited 436 postmenopausal Chinese Han women receiving adjuvant AIs therapy for early-stage hormone-sensitive breast cancer. Patients completed a self-administered questionnaire assessing the presence of musculoskeletal symptoms that started or worsened after initiating AIs. 27 single nucleotide polymorphisms (SNP) of ESR1, ESR2 and PGR were analyzed by Sequenom MassARRAY assays and /or PCR-based TaqMan assays.Of the 436 enrolled women, 206 cases experienced musculoskeletal symptoms.Patients who received taxane chemotherapy were more than two times more likely than other patients to have AIs-related MS-AEs. Genetic assay had showed that only two ESR1 SNPs, rs2234693 and rs9340799 were associated with AIs-related MS-AEs.TT genotype and the T allele in rs2234693 was statistically significantly lower in AIs-Related MS-AEs group than controls (P = 0.001; P = 9.49E-7). The frequency of AA genotype and the A allele in rs9340799 was higher (P = 2.20E-5; P = 3.09E-4).. Our results suggested that prior taxane-based chemotherapy was the clinical predictor, while rs2234693 and rs9340799 were the genetic predictors for AIs-related MS-AEs.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Antineoplastic Agents; Aromatase Inhibitors; Asian People; Breast Neoplasms; Bridged-Ring Compounds; Case-Control Studies; China; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Middle Aged; Musculoskeletal Diseases; Neoplasm Staging; Odds Ratio; Polymorphism, Single Nucleotide; Postmenopause; Receptors, Progesterone; Taxoids

The aromatase inhibitor (AI)-associated musculoskeletal syndrome (AIMSS) occurs in approximately 50% of AI-treated patients. Inflammatory mediators are associated with oestrogen signalling and may change with oestrogen depletion. We hypothesised that AIMSS may be associated with changes in circulating inflammatory markers.. Patients with breast cancer were enrolled in a trial of adjuvant AI therapy. Changes in pain and function during therapy were assessed prospectively. We selected 30 cases with AIMSS and 22 controls without AIMSS, matched for demographics and prior therapy. Serum samples collected at baseline and during treatment were assayed for multiple inflammatory cytokines and lipid mediators using multiplex assays.. Before AI therapy, mean serum concentrations of 6 of 36 assayed factors were statistically significantly lower in cases than controls (all P<0.003). No statistically significant changes during AI therapy relative to pre-treatment were observed between cases and controls for any of the inflammatory markers tested.. AIMSS is probably not associated with a systemic inflammatory response. Pre-treatment cytokine levels may predict for development of AIMSS.

Topics: Aged; Androstadienes; Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Bridged-Ring Compounds; Case-Control Studies; Cytokines; Estrogens; Female; Humans; Inflammation; Middle Aged; Musculoskeletal Diseases; Postmenopause; Syndrome; Tamoxifen; Taxoids