• DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.

      Mateo, J; Carreira, S; Sandhu, S; Miranda, S; Mossop, H; Perez-Lopez, R; Nava Rodrigues, D; Robinson, D; Omlin, A; Tunariu, N; et al. (2015-10-29)
      Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would respond to poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibition with olaparib.
    • Induction of apoptosis by tamoxifen and ICI 182780 in primary breast cancer.

      Ellis, P A; Saccani-Jotti, G; Clarke, Robert B; Johnston, S R; Anderson, Elizabeth; Howell, Anthony; A'Hern, R; Salter, J; Detre, S; Nicholson, R; et al. (1997-08-07)
      Hormonal breast cancer therapies have traditionally been considered cytostatic, but recent pre-clinical data suggest that anti-oestrogens can induce apoptosis. The aim of this study was to assess whether tamoxifen (TAM) and ICI 182780 (ICI) could induce apoptosis in human breast cancer, and whether this was related to oestrogen receptor status. We measured apoptosis in primary breast cancer patients before and after pre-surgical treatment with 20 mg/day TAM (study 1) or 6 or 18 mg/day ICI (study 2). In each study there was a randomised non-treatment (NT) control group. TAM significantly increased apoptotic index (AI) in ER+ but not in ER- tumours. There was a significant increase in AI following treatment with ICI. Insufficient pairs of samples were available to determine whether this change was confined to ER+ tumours, but in a cross-sectional analysis AI was significantly higher in excision biopsies for ICI-treated than NT patients for ER+ but not ER- tumours. Our results provide clinical evidence that apoptosis may be induced in ER+ primary breast cancer by both non-steroidal and steroidal anti-oestrogens.
    • Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial.

      Nutting, C; Morden, J; Harrington, K; Urbano, Teresa G; Bhide, S A; Clark, C; Miles, E A; Miah, A B; Newbold, K; Tanay, M A; et al. (2011-02)
      Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.
    • Polymorphisms of CYP19A1 and response to aromatase inhibitors in metastatic breast cancer patients.

      Ferraldeschi, Roberta; Arnedos, M; Hadfield, K D; A'Hern, R; Drury, S; Wardley, Andrew M; Howell, Anthony; Evans, D G; Roberts, S A; Smith, I; et al. (2012-03-15)
      Single nucleotide polymorphisms (SNPs) in the gene encoding aromatase (CYP19A1) have been associated with differential benefit from letrozole treatment in metastatic breast cancer (mBC) patients, but validation is lacking. The aim was to investigate whether polymorphic variation of CYP19A1 and enzymes involved in estrogen and aromatase inhibitors (AIs) metabolism are associated with efficacy of AIs. 308 Women with estrogen-receptor-positive metastatic mBC treated with a third-generation AI were identified retrospectively. DNA was extracted from archival formalin-fixed paraffin embedded tumors and genotyped for 71 variants in 16 candidate genes, including CYP19A1. Time to treatment failure (TTF) was significantly improved in patients carrying the minor (T) allele of rs4775936 when compared to patients with the reference allele [HR = 0.79 per T allele (0.66-0.95); P = 0.012]. Patients with >7 TTTA repeats on either allele of CYP19A1 intron 4 had a lower risk of failure than those with a smaller repeat size [HR = 0.84 per >7 TTTA repeats (0.7-0.99); P = 0.04]. However, importantly in multivariate analysis, adjusting for the number of disease sites; disease-free interval from diagnosis to first recurrence, grade at diagnosis and first recurrence type neither variant maintained independent predictive significance. None of the 56 SNPs analyzed as an exploratory set showed significant association with TTF. Variants in CYP19A1 or other selected genes associated with AI metabolism were not independently associated with improved AI efficacy and emphasize the importance in pharmacogenetic studies of considering genetic biomarkers in the context of relevant prognostic factors.
    • Psychological effects of being offered choice of surgery for breast cancer.

      Fallowfield, L J; Hall, A; Maguire, Peter; Baum, M; A'Hern, R; Department of Oncology, University College London Medical School. (1994-08-13)