+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: not found

      Plasma estrone sulfate concentrations and genetic variation at the CYP19A1 locus in postmenopausal women with early breast cancer treated with letrozole

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          Estrogen synthesis suppression induced by aromatase inhibitors in breast cancer (BC) patients may be affected by single nucleotide polymorphisms (SNPs) of the gene encoding aromatase enzyme, CYP19A1. We assessed the association between plasma estrone sulfate (ES), letrozole treatment, and four SNPs of CYP19A1 gene (rs10046 C>T, rs4646 G>T, rs749292 C>T, rs727479 T>G) which seem to be related to circulating estrogen levels. Patients were enrolled into a prospective, Italian multi-center clinical trial (Gruppo Italiano Mammella, GIM-5) testing the association of CYP19A1 SNPs with the efficacy of letrozole adjuvant therapy, in postmenopausal early BC patients. SNPs were identified from peripheral blood cell DNA. Plasma ES concentrations were evaluated by Radio Immuno Assay. Blood samples were obtained immediately before letrozole therapy ( N = 204), at 6-weeks ( N = 178), 6 ( N = 152) and 12-months ( N = 136) during treatment. Medians (IQR) of ES were 160 pg/mL (85–274) at baseline, 35 pg/mL (12–64) at 6-weeks, 29 pg/mL (17–48) at 6 months and 25 pg/mL (8–46) after 12 months treatment. No statistically significant association was evident between polymorphisms and ES circulating levels during letrozole therapy. Letrozole suppression of the aromatase enzyme function is not affected by polymorphisms of CYP19A1 gene in postmenopausal BC patients.

          Related collections

          Most cited references 30

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          Hardy-Weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies

          Mendelian randomization (MR) permits causal inference between exposures and a disease. It can be compared with randomized controlled trials. Whereas in a randomized controlled trial the randomization occurs at entry into the trial, in MR the randomization occurs during gamete formation and conception. Several factors, including time since conception and sampling variation, are relevant to the interpretation of an MR test. Particularly important is consideration of the “missingness” of genotypes that can be originated by chance, genotyping errors, or clinical ascertainment. Testing for Hardy-Weinberg equilibrium (HWE) is a genetic approach that permits evaluation of missingness. In this paper, the authors demonstrate evidence of nonconformity with HWE in real data. They also perform simulations to characterize the sensitivity of HWE tests to missingness. Unresolved missingness could lead to a false rejection of causality in an MR investigation of trait-disease association. These results indicate that large-scale studies, very high quality genotyping data, and detailed knowledge of the life-course genetics of the alleles/genotypes studied will largely mitigate this risk. The authors also present a Web program ( for estimating possible missingness and an approach to evaluating missingness under different genetic models.
            • Record: found
            • Abstract: found
            • Article: not found

            Polychemotherapy for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group.

            There have been many randomised trials of adjuvant prolonged polychemotherapy among women with early breast cancer, and an updated overview of their results is presented. In 1995, information was sought on each woman in any randomised trial that began before 1990 and involved treatment groups that differed only with respect to the chemotherapy regimens that were being compared. Analyses involved about 18,000 women in 47 trials of prolonged polychemotherapy versus no chemotherapy, about 6000 in 11 trials of longer versus shorter polychemotherapy, and about 6000 in 11 trials of anthracycline-containing regimens versus CMF (cyclophosphamide, methotrexate, and fluorouracil). For recurrence, polychemotherapy produced substantial and highly significant proportional reductions both among women aged under 50 at randomisation (35% [SD 4] reduction; 2p<0.00001) and among those aged 50-69 (20% [SD 3] reduction; 2p<0.00001); few women aged 70 or over had been studied. For mortality, the reductions were also significant both among women aged under 50 (27% [SD 5] reduction; 2p<0.00001) and among those aged 50-69 (11% [SD 3] reduction; 2p=0.0001). The recurrence reductions emerged chiefly during the first 5 years of follow-up, whereas the difference in survival grew throughout the first 10 years. After standardisation for age and time since randomisation, the proportional reductions in risk were similar for women with node-negative and node-positive disease. Applying the proportional mortality reduction observed in all women aged under 50 at randomisation would typically change a 10-year survival of 71% for those with node-negative disease to 78% (an absolute benefit of 7%), and of 42% for those with node-positive disease to 53% (an absolute benefit of 11%). The smaller proportional mortality reduction observed in all women aged 50-69 at randomisation would translate into smaller absolute benefits, changing a 10-year survival of 67% for those with node-negative disease to 69% (an absolute gain of 2%) and of 46% for those with node-positive disease to 49% (an absolute gain of 3%). The age-specific benefits of polychemotherapy appeared to be largely irrespective of menopausal status at presentation, oestrogen receptor status of the primary tumour, and of whether adjuvant tamoxifen had been given. In terms of other outcomes, there was a reduction of about one-fifth (2p=0.05) in contralateral breast cancer, which has already been included in the analyses of recurrence, and no apparent adverse effect on deaths from causes other than breast cancer (death rate ratio 0.89 [SD 0.09]). The directly randomised comparisons of longer versus shorter durations of polychemotherapy did not indicate any survival advantage with the use of more than about 3-6 months of polychemotherapy. By contrast, directly randomised comparisons did suggest that, compared with CMF alone, the anthracycline-containing regimens studied produced somewhat greater effects on recurrence (2p=0.006) and mortality (69% vs 72% 5-year survival; log-rank 2p=0.02). But this comparison is one of many that could have been selected for emphasis, the 99% CI reaches zero, and the results of several of the relevant trials are not yet available. Some months of adjuvant polychemotherapy (eg, with CMF or an anthracycline-containing regimen) typically produces an absolute improvement of about 7-11% in 10-year survival for women aged under 50 at presentation with early breast cancer, and of about 2-3% for those aged 50-69 (unless their prognosis is likely to be extremely good even without such treatment). Treatment decisions involve consideration not only of improvements in cancer recurrence and survival but also of adverse side-effects of treatment, and this report makes no recommendations as to who should or should not be treated.
              • Record: found
              • Abstract: not found
              • Article: not found

              Polychemotherapy for early breast cancer: an overview of the randomised trials

               Michael Gnant (1998)

                Author and article information

                +390456014621 , +390456013411 ,
                Breast Cancer Res Treat
                Breast Cancer Res. Treat
                Breast Cancer Research and Treatment
                Springer US (Boston )
                6 November 2012
                6 November 2012
                January 2013
                : 137
                : 1
                : 167-174
                [ ]Oncology Unit, Ospedale Sacro Cuore Don Calabria, Via Sempreboni, 5, 37024 Negrar, VR Italy
                [ ]IRCSS AOU San Martino - IST, Genoa, Italy
                [ ]Tumor Institute of Tuscany, Florence, Italy
                [ ]Azienda Ospedaliero Universitaria di Udine, Udine, Italy
                [ ]S. Anna Hospital, Turin, Italy
                [ ]Institute for Cancer Research and Treatment of Candiolo, Turin, Italy
                [ ]Azienda Ospedaliera S.Maria Nuova, Reggio Emilia, Italy
                [ ]ASO S. Croce e Carle, Cuneo, Italy
                [ ]Ospedale Carlo Poma, Mantua, Italy
                [ ]E.O. Ospedali Galliera, Genoa, Italy
                © The Author(s) 2012
                Clinical Trial
                Custom metadata
                © Springer Science+Business Media New York 2012


                Comment on this article