RESUMO
BACKGROUND: Aromatase inhibitor (AI) therapy is associated with musculoskeletal (MS) toxicity, which adversely affects quality of life and therapy adherence. Our objective was to evaluate whether genetic variants may predict endocrine therapy-related MS pain and hot flashes in a prospective observational cohort study. PATIENTS & METHODS: 254 early breast cancer patients starting AI (n = 159) or tamoxifen therapy (n = 95) were included in this genetic biomarker study. MS and vasomotor symptoms were assessed at baseline and after 3, 6 and 12 months of therapy. AI-induced MS pain was defined as an increase in arthralgia or myalgia relative to baseline. Single nucleotide polymorphisms (SNP) in candidate genes involved in oestrogen signalling or previously associated with AI-related MS pain or oestrogen levels were selected. RESULTS: Overall, 13 SNPs in CYP19, CYP17, osteoprotegerin (OPG) and oestrogen receptor 1 exhibited an allele frequency >0.05 and were included in the analysis. Patients carrying the G allele of rs2073618 in OPG experienced significantly more AI-induced MS toxicity compared to the wildtype allele, after correction for multiple testing (P = 0.046). Furthermore, this SNP was associated with severity of pain (P = 0.018). No association was found with regard to the other SNPs, both in AI and tamoxifen-treated patients. Neither could an association with vasomotor symptoms be demonstrated. CONCLUSION: The SNP rs2073618 in OPG is associated with an increased risk of MS symptoms and pain with AI therapy, which has not been reported previously. Validation of this finding in larger cohorts and further functional studies are required.
Assuntos
Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Dor Musculoesquelética/induzido quimicamente , Dor Musculoesquelética/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Artralgia/induzido quimicamente , Artralgia/genética , Neoplasias da Mama/enzimologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Dor Musculoesquelética/diagnóstico , Mialgia/induzido quimicamente , Mialgia/genética , Medição da Dor , Fenótipo , Estudos Prospectivos , Fatores de Risco , Fatores de TempoRESUMO
OBJECTIVES: It is still unclear whether residual defects seen after carotid endarterectomy (CEA) have clinical consequences. We investigated prevalence of residual defects in the carotid artery and their possible impact on clinical and Duplex ultrasound (DUS) follow-up. MATERIALS AND METHODS: Sixty-five patients who had undergone CEA were prospectively examined with 1-3 month postoperative computed tomographic angiography (CTA), clinical and DUS follow-up. Defects in common (CCA), external (ECA) and internal carotid artery (ICA) were scored as clamp marks, intimal step or flap, mural thrombus, kink, microdehiscence suture or residual stenosis. RESULTS: Fifty-eight patients (89.2%) had residual defects in CCA, ECA or ICA (143 defects). Intimal steps (n = 39) and residual stenosis (n = 17) were most noted defects. Only residual defects in ECA were significantly associated with significant higher PSV values both at short-term and long-term follow-up (1990 vs. 1400 mm s(-1) at 1 year and 2000 vs. 1230 mm s(-1) at 2 years, P-values 0.031 and 0.016). CONCLUSION: Carotid artery residual defects on CTA after CEA are very common, simple fingerprints of the operative procedure, have no clear consequence. When CTA is performed clinically after CEA, knowledge of high prevalence and type of defects detected on CTA may be of importance for radiologists and clinicians.