Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial.
MetadataShow full item record
The randomized, double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. Eligible participants (<i>n</i> = 2,471) were randomly assigned to tamoxifen (20 mg/d) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of estrogen receptor (ER)-positive invasive breast cancer mostly in the posttreatment period. Biomarker analysis in this population may identify any subgroup-specific preventive effects tamoxifen. After a median follow-up of 18.4 years, 242 patients had developed invasive cancer, 134 on placebo and 108 on tamoxifen. From these, 180 tissue blocks were available and ER, progesterone receptor (PgR), Ki67, HER2, and EGFR were immunohistochemically analyzed. A 32% reduction in ER<sup>+</sup> and PgR<sup>+</sup> invasive cancers resulted after 8 years of treatment. Quantitative levels of ER and PgR were lower in the tamoxifen-treated group, significantly so for ER (<i>P</i> = 0.001). These lower ER levels were restricted to the posttreatment period (<i>P</i> = 0.018). Among the ER<sup>+</sup> group, there was a similar proportional decrease in PgR<sup>+</sup> and PgR<sup>-</sup> tumors by tamoxifen. The median levels of Ki67 were similar in both arms. The numbers of HER2-positive and EGFR-positive cancers were higher in the tamoxifen arm but not significantly so. In conclusion, the preventive effects of tamoxifen result in reduced ER-positive but not ER-negative tumors and reduced ER expression in the ER-positive cases largely confined to the posttreatment period. Overall reductions in PgR expression are explained by lower frequency of ER-positive cases. Impact on Ki67, HER2, and EGFR was modest. <i>Cancer Prev Res; 10(3); 171-6. ©2017 AACR</i>.
Version of record
Selective Estrogen Receptor Modulators
Medicine (RMH Smith Cunningham)
License start date
Cancer prevention research (Philadelphia, Pa.), 2017, 10 (3), pp. 171 - 176
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Showing items related by title, author, creator and subject.
Calcinotto, A; Spataro, C; Zagato, E; Di Mitri, D; Gil, V; Crespo, M; De Bernardis, G; Losa, M; Mirenda, M; Pasquini, E; Rinaldi, A; Sumanasuriya, S; Lambros, MB; Neeb, A; Lucianò, R; Bravi, CA; Nava-Rodrigues, D; Dolling, D; Prayer-Galetti, T; Ferreira, A; Briganti, A; Esposito, A; Barry, S; Yuan, W; Sharp, A; de Bono, J; Alimonti, A (2018-07)Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control ...
A genomic approach to therapeutic target validation identifies a glucose-lowering GLP1R variant protective for coronary heart disease. Scott, RA; Freitag, DF; Li, L; Chu, AY; Surendran, P; Young, R; Grarup, N; Stancáková, A; Chen, Y; Varga, TV; Yaghootkar, H; Luan, J; Zhao, JH; Willems, SM; Wessel, J; Wang, S; Maruthur, N; Michailidou, K; Pirie, A; van der Lee, SJ; Gillson, C; Al Olama, AA; Amouyel, P; Arriola, L; Arveiler, D; Aviles-Olmos, I; Balkau, B; Barricarte, A; Barroso, I; Garcia, SB; Bis, JC; Blankenberg, S; Boehnke, M; Boeing, H; Boerwinkle, E; Borecki, IB; Bork-Jensen, J; Bowden, S; Caldas, C; Caslake, M; CVD50 consortium; Cupples, LA; Cruchaga, C; Czajkowski, J; den Hoed, M; Dunn, JA; Earl, HM; Ehret, GB; Ferrannini, E; Ferrieres, J; Foltynie, T; Ford, I; Forouhi, NG; Gianfagna, F; Gonzalez, C; Grioni, S; Hiller, L; Jansson, J-H; Jørgensen, ME; Jukema, JW; Kaaks, R; Kee, F; Kerrison, ND; Key, TJ; Kontto, J; Kote-Jarai, Z; Kraja, AT; Kuulasmaa, K; Kuusisto, J; Linneberg, A; Liu, C; Marenne, G; Mohlke, KL; Morris, AP; Muir, K; Müller-Nurasyid, M; Munroe, PB; Navarro, C; Nielsen, SF; Nilsson, PM; Nordestgaard, BG; Packard, CJ; Palli, D; Panico, S; Peloso, GM; Perola, M; Peters, A; Poole, CJ; Quirós, JR; Rolandsson, O; Sacerdote, C; Salomaa, V; Sánchez, M-J; Sattar, N; Sharp, SJ; Sims, R; Slimani, N; Smith, JA; Thompson, DJ; Trompet, S; Tumino, R; van der A, DL; van der Schouw, YT; Virtamo, J; Walker, M; Walter, K; GERAD_EC Consortium; Neurology Working Group of the Cohorts for Heart; Aging Research in Genomic Epidemiology (CHARGE); Alzheimer’s Disease Genetics Consortium; Pancreatic Cancer Cohort Consortium; European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease (EPIC-CVD); EPIC-InterAct; Abraham, JE; Amundadottir, LT; Aponte, JL; Butterworth, AS; Dupuis, J; Easton, DF; Eeles, RA; Erdmann, J; Franks, PW; Frayling, TM; Hansen, T; Howson, JMM; Jørgensen, T; Kooner, J; Laakso, M; Langenberg, C; McCarthy, MI; Pankow, JS; Pedersen, O; Riboli, E; Rotter, JI; Saleheen, D; Samani, NJ; Schunkert, H; Vollenweider, P; O'Rahilly, S; CHARGE consortium; CHD Exome+ Consortium; CARDIOGRAM Exome Consortium; Deloukas, P; Danesh, J; Goodarzi, MO; Kathiresan, S; Meigs, JB; Ehm, MG; Wareham, NJ; Waterworth, DM (2016-06)Regulatory authorities have indicated that new drugs to treat type 2 diabetes (T2D) should not be associated with an unacceptable increase in cardiovascular risk. Human genetics may be able to guide development of antidiabetic ...
Intracavitary 'T4 immunotherapy' of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells. Klampatsa, A; Achkova, DY; Davies, DM; Parente-Pereira, AC; Woodman, N; Rosekilly, J; Osborne, G; Thayaparan, T; Bille, A; Sheaf, M; Spicer, JF; King, J; Maher, J (2017-05)Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. ...