191 results on '"George WD"'
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2. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years
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Pan, H, Gray, R, Braybrooke, J, Davies, C, Taylor, C, Mcgale, P, Peto, R, Pritchard, Ki, Bergh, J, Dowsett, M, Hayes, Df, Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bartlett, J, Bergsten‐nordström, E, Bliss, J, Boccardo, F, Bradley, R, Brain, E, Cameron, D, Clarke, M, Coates, A, Coleman, R, Correa, C, Costantino, J, Cuzick, J, Davidson, N, Dodwell, D, Di Leo, A, Ewertz, M, Forbes, J, Gelber, R, Gnant, M, Goldhirsch, A, Goodwin, P, Hill, C, Ingle, J, Jagsi, R, Janni, W, Loibl, S, Mackinnon, E, Martin, M, Mukai, H, Norton, L, Ohashi, Y, Paik, S, Perez, E, Piccart, M, Pierce, L, Poortmans, P, Raina, V, Ravdin, P, Regan, M, Robertson, J, Rutgers, E, Slamon, D, Sparano, J, Swain, S, Tutt, A, Viale, G, Von Minckwitz, G, Wang, X, Whelan, T, Wilcken, N, Winer, E, Wolmark, N, Wood, W, Zambetti, M, Alberro, Ja, Ballester, B, Deulofeu, P, Fábregas, R, Fraile, M, Gubern, Jm, Janer, J, Moral, A, De Pablo Jl, Peñalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Solà, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Garaud, P, Collett, V, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hma, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Hupperets, Psgj, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Dal, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bramwell, Vh, Chen, Be, Gelmon, K, Goss, Pe, Levine, Mn, Parulekar, W, Pater, Jl, Shepherd, Le, Tu, D, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu‐zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett‐lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec’h, J, De La Lande, B, Mouret‐fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Boddington, C, Burrett, Ja, Cutter, D, Duane, F, Evans, V, Gettins, L, Godwin, J, James, S, Kerr, A, Liu, H, Mannu, G, Mchugh, T, Morris, P, Read, S, Wang, Y, Wang, Z, Albano, J, De Oliveira Cf, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Mouridsen, Ht, Fehm, T, Trampisch, Hj, Dalesio, O, De Vries Ege, Rodenhuis, S, Van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jgm, Treurniet‐donker, Ad, Van Putten Wlj, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Van De Velde Cjh, Cunningham, Mp, Brufsky, Am, Coleman, Re, Llombart, Ha, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Carrasco, E, Segui, Ma, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, De Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Galligioni, E, Leone, B, Vallejo, Ct, Zwenger, A, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, De Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Delaloge, S, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, Van De Velde Ao, Van Dongen Ja, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Bighin, C, Bruzzi, P, Del Mastro, L, Dozin, B, Pastorino, S, Pronzato, P, Sertoli, Mr, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro Mg, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, Ah, Kohno, N, Miyashita, M, Takao, S, Ahn, Jh, Jung, Kh, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, Gj, Christiaens, R, Neven, P, Paridaens, R, Van Den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, De La Huerta, R, Sainz, Mg, Ro, J, Camphausen, K, Danforth, D, Lichter, A, Lippman, M, Smart, D, Steinberg, S, D’Amico, C, Lioce, M, Paradiso, A, Ohno, S, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Redmond, C, Wickerham, L, Aihara, T, Hozumi, Y, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Venturini, M, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Reinertsen, Kv, Varhaug, Je, Gundersen, S, Hauer‐jensen, M, Høst, H, Nissen‐meyer, R, Mitchell, Ak, Robertson, Jfr, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Cocconi, G, Di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Hadji, P, A’Hern, R, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Clack, G, Van Poznak, C, Deshpande, N, Di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Ajs, Ewing, Gh, Firth, La, Krushen‐kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, Af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ahg, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Lemonnier, J, Martin, Al, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Deutsch, Gp, Kwong, Dlw, Pai, Vr, Senanayake, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Bell, R, Hinsley, S, Marshall, Hc, Pierce, Lj, Solomayer, E, Horsman, Jm, Lester, J, Winter, Mc, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Aft, R, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., Guided Treatment in Optimal Selected Cancer Patients (GUTS), Other departments, CCA - Cancer Treatment and Quality of Life, Radiotherapy, Pan, Hongchao, Gray, Richard, Braybrooke, Jeremy, Davies, Christina, Taylor, Carolyn, Mcgale, Paul, Peto, Richard, Pritchard, Kathleen I, Bergh, Jona, Dowsett, Mitch, Hayes, Daniel F, De Laurentiis, Michelino, MUMC+: MA Medische Oncologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Interne Geneeskunde
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0301 basic medicine ,Oncology ,medicine.medical_treatment ,Kaplan-Meier Estimate ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Recurrence ,Receptors ,Neoplasm Metastasis ,AMERICAN SOCIETY ,Adjuvant ,CLINICAL-PRACTICE GUIDELINE ,Absolute risk reduction ,Estrogen Antagonists ,General Medicine ,Estrogen Antagonist ,CHEMOTHERAPY ,Middle Aged ,Prognosis ,Neoplasm Metastasi ,Local ,POSTMENOPAUSAL WOMEN ,Receptors, Estrogen ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Meta-analysis ,Lymphatic Metastasis ,Female ,Human ,Estrogen Antagonists/therapeutic use ,Adult ,Risk ,medicine.medical_specialty ,Prognosi ,medicine.drug_class ,DISCONTINUATION ,Breast Neoplasms ,Article ,Drug Administration Schedule ,LATE DISTANT RECURRENCE ,03 medical and health sciences ,Breast cancer ,Breast Neoplasms/drug therapy ,Internal medicine ,SCORE ,medicine ,Humans ,SURGICAL ADJUVANT BREAST ,Aged ,Proportional Hazards Models ,Chemotherapy ,business.industry ,Proportional hazards model ,Lymphatic Metastasi ,TAMOXIFEN THERAPY ,ta3122 ,medicine.disease ,Estrogen ,RANDOMIZED-TRIALS ,Discontinuation ,Surgery ,Neoplasm Recurrence ,030104 developmental biology ,Proportional Hazards Model ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business - Abstract
Background The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. Methods In this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years. Results Breast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status. Among the patients with stage T1 disease, the risk of distant recurrence was 13% with no nodal involvement (T1N0), 20% with one to three nodes involved (T1N1–3), and 34% with four to nine nodes involved (T1N4–9); among those with stage T2 disease, the risks were 19% with T2N0, 26% with T2N1–3, and 41% with T2N4–9. The risk of death from breast cancer was similarly dependent on TN status, but the risk of contralateral breast cancer was not. Given the TN status, the factors of tumor grade (available in 43,590 patients) and Ki-67 status (available in 7692 patients), which are strongly correlated with each other, were of only moderate independent predictive value for distant recurrence, but the status regarding the progesterone receptor (in 54,115 patients) and human epidermal growth factor receptor type 2 (HER2) (in 15,418 patients in trials with no use of trastuzumab) was not predictive. During the study period from 5 to 20 years, the absolute risk of distant recurrence among patients with T1N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease; the corresponding risks of any recurrence or a contralateral breast cancer were 17%, 22%, and 26%, respectively. Conclusions After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant recurrence was strongly correlated with the original TN status, with risks ranging from 10 to 41%, depending on TN status and tumor grade. (Funded by Cancer Research UK and others.)
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- 2017
3. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials
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Alberro, JA, Ballester, B, Deulofeu, P, Fabregas, R, Fraile, M, Gubern, JM, Janer, J, Moral, A, de Pablo, JL, Penalva, G, Puig, P, Ramos, M, Rojo, R, Santesteban, P, Serra, C, Sola, M, Solarnau, L, Solsona, J, Veloso, E, Vidal, S, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Coles, CE, Haybittle, JL, Moebus, V, Leonard, CF, Calais, G, Garaud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, VJ, Holdaway, IM, Kay, RG, Mason, BH, Forbe, JF, Franci, PA, Wilcken, N, Balic, M, Bartsch, R, Fesl, C, Fitzal, F, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Marth, C, Mlineritsch, B, Pfeiler, G, Singer, CF, Steger, GG, Stoeger, H, Canney, P, Yosef, HMA, Focan, C, Peek, U, Oates, GD, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, JM, Philippson, C, Piccart, MJ, Masood, MB, Parker, D, Price, JJ, Lindsay, MA, Mackey, J, Martin, M, Hupperets, PSGJ, Bates, T, Blamey, RW, Chetty, U, Ellis, IO, Mallon, E, Morgan, DAL, Patnick, J, Pinder, S, Lohrisch, C, Nichol, A, Bartlett, JMS, Bramwell, VH, Chen, BE, Chia, SKL, Gelmon, K, Goss, PE, Levine, MN, Parulekar, W, Pater, JL, Pritchard, KI, Shepherd, LE, Tu, D, Whelan, T, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, RB, Abu-Zahara, HT, Karpov, A, Portnoj, SL, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, PJ, Manse, RE, Monypenny, IJ, Gordon, NH, Davis, HL, Cuzick, J, Sestak, I, Lehingue, Y, Romestaing, P, Dubois, JB, Delozier, T, Griffon, B, Lesec'h, J Mace, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, JR, Meier, P, Shan, Y, Shao, YF, Wang, X, Zhao, DB, Howell, A, Swindell, R, Albano, J, de Oliveira, CF, Gervasio, H, Gordilho, J, Ejlertsen, B, Jensen, M-B, Mouridsen, H, Gelman, RS, Harris, JR, Hayes, D, Henderson, C, Shapiro, CL, Christiansen, P, Ewertz, M, Jensen, MB, Mouridsen, HT, Fehm, T, Trampisch, HJ, Dalesio, O, de Vries, EGE, Rodenhuis, S, van Tinteren, H, Comis, RL, Davidson, NE, Gray, R, Robert, N, Sledge, G, Solin, LJ, Sparano, JA, Tormey, DC, Wood, W, Cameron, D, Dixon, JM, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, JGM, Treurniet-Donker, AD, van Putten, WLJ, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, JP, Poortmans, PM, Rutgers, E, van de Velde, CJH, Cunningham, MP, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, LJ, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Lupors, E, Namer, M, Carrasco, E, Segui, MA, Eierman, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, JU, Costa, SD, Eidtmann, H, Gerber, B, Jackisch, C, Loib, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, MC, Sacco, M, Valentini, M, McArdle, CS, Smith, DC, Stallard, S, Dent, DM, Gudgeon, CA, Hacking, A, Murray, E, Panieri, E, Werner, ID, De Salvo, GL, Del Bianco, P, Zavagno, G, Leone, B, Vallejo, CT, Zwenger, A, Galligioni, E, Lopez, M, Erazo, A, Medina, JY, Horiguchi, J, Takei, H, Fentiman, IS, Hayward, JL, Rubens, RD, Skilton, D, Scheurlen, H, Sohn, HC, Untch, M, Dafni, U, Markopoulos, C, Bamia, C, Fountzilas, G, Koliou, G-A, Manousou, K, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Canavese, G, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roche, H, Asselain, B, Salmon, RJ, Vilcoq, JR, Brain, E, de La Lande, B, Mouret-Fourme, E, Andre, F, Arriagada, R, Delaloge, S, Hill, C, Koscienly, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, JR, Benraadt, J, Kooi, M, van de Velde, AO, van Dongen, JA, Vermorken, JB, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelbe, RD, Goldhirsch, A, Lindtner, J, Price, KN, Regan, MM, Rudenstam, CM, Senn, HJ, Thuerlimann, B, Bliss, JM, Chilvers, CED, Coombes, RC, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, WD, Stewart, HJ, Stroner, P, Borovik, R, Hayat, H, Inbar, MJ, Peretz, T, Robinson, E, Camerini, T, Formelli, F, Martelli, G, Di Mauro, MG, Perrone, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Musolino, A, Passalacqua, R, Iwata, H, Shien, T, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Sadoon, M, Tulusan, AH, Kohno, N, Miyashita, M, Takao, S, Ahn, J-H, Jung, KH, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, Liefers, GJ, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Gazet, JC, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Host, H, Lindtner, A, Notter, G, Bryant, AJS, Ewing, GH, Firth, LA, Krushen-Kosloski, JL, Nissen-Meyer, R, Anderson, H, Killander, F, Malmstrom, P, Ryden, L, Arnesson, L-G, Carstense, J, Dufmats, M, Fohlin, H, Nordenskjold, B, Soderberg, M, Sundqvist, M, Carpenter, TJ, Murray, N, Royle, GT, Simmonds, PD, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, CK, Ravdin, PM, Bergh, J, Bondesso, T, Celebiogl, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Goransson, E, Iiristo, M, Johansson, U, Lenner, E, Lofgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadstrom, C, Janni, W, Maibach, R, Thurlimann, B, Hadji, P, Hozumi, J, Holli, K, Rouhento, K, Safra, T, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, AHG, Fyles, A, Meakin, JW, Panzarella, T, Bahi, J, Lemonnier, J, Martin, AL, Reid, M, Spittle, M, Bishop, H, Bundred, NJ, Forbes, JF, Forsyth, S, George, WS, Pinder, SE, Deutsch, GP, Kwong, DLW, Pai, VR, Peto, R, Senanayake, F, Boccardo, F, Rubagotti, A, Baum, M, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, JS, Carlomagno, C, De Laurentiis, M, De Placido, S, Schem, C, Williams, L, Bell, R, Coleman, RE, Dodwell, D, Hinsley, S, Marshall, HC, Pierce, LJ, Basso, SMM, Lumachi, F, Solomayer, E, Horsman, JM, Lester, J, Winter, MC, Buzdar, AU, Hsu, L, Love, RR, Ahlgren, J, Garmo, H, Holmberg, L, Lindman, H, Warnberg, F, Asmar, L, Jones, SE, Aft, R, Gluz, O, Harbeck, N, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, BK, Chlebowski, RT, Caffier, H, Brufsky, AM, Llombart, HA, Asselain, B, Barlow, W, Bartlett, J, Bradley, R, Braybrooke, J, Davies, C, Dodwell, D, Gray, R, Mannu, G, Taylor, C, Peto, R, McGale, P, Pan, H, Wang, Y, Wang, Z, Department of Oncology, Clinicum, HUS Comprehensive Cancer Center, Medical Oncology, Cancer Research UK, and Pfizer Limited
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0301 basic medicine ,Oncology ,Time Factors ,SURGERY ,medicine.medical_treatment ,menopause ,chemotherapy ,Mastectomy, Segmental ,Rate ratio ,THERAPY ,aromatase inhibitors ,CEA ,0302 clinical medicine ,Risk Factors ,Medicine and Health Sciences ,Breast ,Neoplasm Metastasis ,Randomized Controlled Trials as Topic ,RISK ,tamoxifen ,breast tumor ,CA15-3 ,axillary dissection ,mastectomy ,Middle Aged ,Neoadjuvant Therapy ,METHOTREXATE ,3. Good health ,trastuzumab ,Treatment Outcome ,quadrantectomy ,Chemotherapy, Adjuvant ,axillary lymphnodes ,030220 oncology & carcinogenesis ,Meta-analysis ,SURVIVAL ,Disease Progression ,Female ,Life Sciences & Biomedicine ,axillary clearance ,RADIOTHERAPY ,medicine.drug ,Adult ,medicine.medical_specialty ,Anthracycline ,3122 Cancers ,Antineoplastic Agents ,Breast Neoplasms ,axillary nodes ,sentinel node biopsy ,03 medical and health sciences ,breast cancer ,Breast cancer ,SDG 3 - Good Health and Well-being ,HER2 ,Internal medicine ,Journal Article ,medicine ,cancer ,Humans ,Breast, breast cancer, breast diseases, cancer, malignancy, menopause, surgery, mastectomy, quadrantectomy, lumpectomy, axillary nodes, axillary lymphnodes, axillary dissection, axillary clearance, sentinel node biopsy, sentinel node, BRCA1, BRCA2, tamoxifen, aromatase inhibitors, breast tumor, osteoporosis, bisphosphonates, denosumab, trastuzumab, HER2, CEA, CA15-3, tumor marker, chemotherapy, endocrine therapy ,Oncology & Carcinogenesis ,RECURRENCE ,bisphosphonates ,Pathological ,Neoplasm Staging ,lumpectomy ,Chemotherapy ,Science & Technology ,breast diseases ,endocrine therapy ,business.industry ,denosumab ,BRCA1 ,medicine.disease ,BRCA2 ,osteoporosis ,Radiation therapy ,STIMULATING FACTOR ,030104 developmental biology ,sentinel node ,tumor marker ,Methotrexate ,Neoplasm Recurrence, Local ,business ,1112 Oncology And Carcinogenesis ,malignancy - Abstract
BACKGROUND: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials. METHODS: We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality). FINDINGS: Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45). INTERPRETATION: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy. FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health. ispartof: LANCET ONCOLOGY vol:19 issue:1 pages:27-39 ispartof: location:England status: published
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- 2017
4. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials
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Mcgale, P., Taylor, C., Correa, C., Cutter, D., Duane, F., Ewertz, M., Gray, R., Mannu, G., Peto, R., Whelan, T., Wang, Y., Wang, Z., Darby, S., Albain, K., Anderson, S., Arriagada, R., Barlow, W., Bergh, J., Bergsten Nordström, E., Bliss, J., Burrett, J. A., Buyse, M., Cameron, D., Carrasco, E., Clarke, M., Coleman, R., Coates, A., Collins, R., Costantino, J., Cuzick, J., Davidson, N., Davies, C., Davies, K., Delmestri, A., Di Leo, A., Dowsett, M., Elphinstone, P., Evans, V., Forbes, J., Gelber, R., Gettins, L., Geyer, C., Gianni, L., Gnant, M., Goldhirsch, A., Godwin, J., Gregory, C., Hayes, D., Hill, C., Ingle, J., Jakesz, R., James, S., Janni, W., Kaufmann, M., Kerr, A., Liu, H., Mackinnon, E., Martín, M., Mchugh, T., Morris, P., Norton, L., Ohashi, Y., Paik, S., Pan, H. C., Perez, E., Piccart, M., Pierce, L., Pritchard, K., Pruneri, G., Raina, V., Ravdin, P., Robertson, J., Rutgers, E., Shao, Y. F., Sparano, J., Swain, S., Valagussa, P., Viale, G., Von Minckwitz, G., Winer, E., Wiang, X., Wood, Abe O, W., Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Ohashi, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Geraud, P, Collett, V, Davies, C, Delmestri, A, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Gnant, M, Greil, R, Jakesz, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hm, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Di Leo, A, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Martin, M, Hupperets, Ps, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Da, Patnick, J, Pinder, S, Olivotto, I, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Norton, L, Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Cuzick, J, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesech, J, Brain, E, de La Lande, B, Mouret-Fourme, E, Mustacchi, G, Petruzelka, L, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Shao, Yf, Wang, X, Zhao, Db, Chen, Zm, Pan, Hc, Howell, A, Swindell, R, Burrett, Ja, Clarke, M, Collins, R, Correa, C, Cutter, D, Darby, S, Davies, K, Elphinstone, P, Evans, V, Gettins, L, Godwin, J, Gray, R, Gregory, C, Hermans, D, Hicks, C, James, S, Kerr, A, Liu, H, Mackinnon, E, Lay, M, Mcgale, P, Mchugh, T, Morris, P, Peto, R, Taylor, C, Wang, Y, Albano, J, de Oliveira CF, Gervásio, H, Gordilho, J, Ejlertsen, B, Jensen, Mb, Johansen, H, Mouridsen, H, Palshof, T, Gelman, Rs, Harris, Jr, Hayes, D, Henderson, C, Shapiro, Cl, Winer, E, Christiansen, P, Ewertz, M, Møller, S, Mouridsen, Ht, Trampisch, Hj, Dalesio, O, de Vries EG, Rodenhuis, S, van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Wood, W, Cameron, D, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jg, Treurniet-Donker, Ad, van Putten WL, Rotmensz, N, Veronesi, U, Viale, G, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, Rutgers, E, van de Velde CJ, Cunningham, Mp, Huovinen, R, Joensuu, H, Costa, A, Bonadonna, G, Gianni, L, Valagussa, P, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, B, Jackisch, C, Loibl, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Carrasco, E, Segui, Ma, Galligioni, E, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Fountzilas, G, Mavroudis, D, Klefstrom, P, Blomqvist, C, Saarto, T, Gallen, M, Tinterri, C, Margreiter, R, de Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, André, F, Arriagada, R, Delaloge, S, Hill, C, Koscielny, S, Michiels, S, Rubino, C, A'Hern, R, Bliss, J, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, van de Velde AO, van Dongen JA, Vermorken, Jb, Castiglione, M, Coates, A, Colleoni, M, Collins, J, Forbes, J, Gelber, Rd, Goldhirsch, A, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ce, Coombes, Rc, Hall, E, Marty, M, Buyse, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Peretz, T, Robinson, E, Bruzzi, P, Del Mastro, L, Pronzato, P, Sertoli, Mr, Venturini, M, Camerini, T, De Palo, G, Di Mauro MG, Formelli, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Cocconi, G, Colozza, A, Passalacqua, R, Aogi, K, Takashima, S, Abe, O, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, van de Water, W, van Nes JG, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Braun, S, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, de la Huerta, R, Sainz, Mg, Altemus, R, Camphausen, K, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, Lj, Steinberg, S, Venzon, D, Zujewski, Ja, D'Amico, C, Lioce, M, Paradiso, A, Chapman, Ja, Gelmon, K, Goss, Pe, Levine, Mn, Meyer, R, Parulekar, W, Pater, Jl, Pritchard, Ki, Shepherd, Le, Tu, D, Whelan, T, Ohno, S, Anderson, S, Bass, G, Brown, A, Bryant, J, Costantino, J, Dignam, J, Fisher, B, Geyer, C, Mamounas, Ep, Paik, S, Redmond, C, Swain, S, Wickerham, L, Wolmark, N, Baum, M, Jackson, Im, Palmer, Mk, Perez, E, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Varhaug, Je, Gundersen, S, Hauer-Jensen, M, Høst, H, Nissen-Meyer, R, Reinertsen, K, Mitchell, Ak, Robertson, Jf, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Dowsett, M, Makris, A, Parton, M, Pennert, K, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Businico, A, Deshpande, N, di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Aj, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Albain, K, Barlow, W, Crowley, J, Gralow, J, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Ravdin, Pm, Adolfsson, J, Bergh, J, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadström, C, Janni, W, Maibach, R, Thürlimann, B, Hakama, M, Holli, K, Isola, J, Rouhento, K, Saaristo, R, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ah, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Sestak, I, Deutsch, Gp, Kwong, Dl, Pai, Vr, Senanayake, F, Martin, Al, Boccardo, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Broglio, K, Buzdar, Au, Hsu, L, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H., McGale, P, Taylor, C, Correa, C, Cutter, D, Duane, F, Ewertz, M, Gray, R, Mannu, G, Peto, R, Whelan, T, Wang, Y, Wang, Z, Darby, S, Biomedische Technologie, RS: GROW - Oncology, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Mcgale, P, DE LAURENTIIS, Michelino, Other departments, CCA -Cancer Center Amsterdam, and Radiotherapy
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medicine.medical_specialty ,medicine.medical_treatment ,Breast Neoplasms ,Rate ratio ,Lower risk ,Systemic therapy ,Statistical significance ,Medicine ,Humans ,Mastectomy ,Randomized Controlled Trials as Topic ,business.industry ,Articles ,General Medicine ,Surgery ,Radiation therapy ,Axilla ,Neoplasm Recurrence ,medicine.anatomical_structure ,Local ,Meta-analysis ,Lymphatic Metastasis ,Lymph Node Excision ,Female ,Neoplasm Recurrence, Local ,business ,Breast Neoplasm ,Human - Abstract
BACKGROUND: Postmastectomy radiotherapy was shown in previous meta-analyses to reduce the risks of both recurrence and breast cancer mortality in all women with node-positive disease considered together. However, the benefit in women with only one to three positive lymph nodes is uncertain. We aimed to assess the effect of radiotherapy in these women after mastectomy and axillary dissection.METHODS: We did a meta-analysis of individual data for 8135 women randomly assigned to treatment groups during 1964-86 in 22 trials of radiotherapy to the chest wall and regional lymph nodes after mastectomy and axillary surgery versus the same surgery but no radiotherapy. Follow-up lasted 10 years for recurrence and to Jan 1, 2009, for mortality. Analyses were stratified by trial, individual follow-up year, age at entry, and pathological nodal status.FINDINGS: 3786 women had axillary dissection to at least level II and had zero, one to three, or four or more positive nodes. All were in trials in which radiotherapy included the chest wall, supraclavicular or axillary fossa (or both), and internal mammary chain. For 700 women with axillary dissection and no positive nodes, radiotherapy had no significant effect on locoregional recurrence (two-sided significance level [2p]>0·1), overall recurrence (rate ratio [RR], irradiated vs not, 1·06, 95% CI 0·76-1·48, 2p>0·1), or breast cancer mortality (RR 1·18, 95% CI 0·89-1·55, 2p>0·1). For 1314 women with axillary dissection and one to three positive nodes, radiotherapy reduced locoregional recurrence (2pINTERPRETATION: After mastectomy and axillary dissection, radiotherapy reduced both recurrence and breast cancer mortality in the women with one to three positive lymph nodes in these trials even when systemic therapy was given. For today's women, who in many countries are at lower risk of recurrence, absolute gains might be smaller but proportional gains might be larger because of more effective radiotherapy.FUNDING: Cancer Research UK, British Heart Foundation, UK Medical Research Council.
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- 2016
5. ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer
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Pinhel, I, Hills, M, Drury, S, Salter, J, Sumo, G, A'Hern, R, Bliss, JM, Sestak, I, Cuzick, J, Barrett-Lee, P, Harris, A, Dowsett, M, Bliss, M, Johnson, L, Lawrence, D, Price, D, Peto, J, Yarnold, J, Brunt, AM, Dodwell, D, Earl, H, Fernando, I, Foster, L, George, WD, Harnett, AM, Perren, T, Poole, C, Raina, V, and Robinson, A
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skin and connective tissue diseases ,neoplasms - Abstract
Introduction: Estrogen receptor-α (ER) and human epidermal growth factor receptor 2 (HER2) positivity are inversely correlated by standard criteria. However, we investigated the quantitative relation between ER and HER2 expression at both RNA and protein levels in HER2+ve and HER2-ve breast carcinomas.Methods: ER and HER2 levels were assessed with immunohistochemistry (IHC) and (for HER2) fluorescent in situ hybridization (FISH) and by quantitative reverse transcription-polymerase chain reaction (q-RT-PCR) in formalin-fixed primary breast cancers from 448 patients in the National Cancer Research Institute (NCRI) Adjuvant Breast Cancer Trial (ABC) tamoxifen-only arm. Relations at the RNA level were assessed in 1,139 TransATAC tumors.Results: ER and HER2 RNA levels were negatively correlated as expected in HER2+ve (IHC 3+ and/or FISH-amplified) tumors (r = -0.45; P = 0.0028). However, in HER2-ve tumors (ER+ve and ER-ve combined), a significant positive correlation was found (r = 0.43; P < 0.0001), HER2 RNA levels being 1.74-fold higher in ER+ve versus ER-ve tumors. This correlation was maintained in the ER+veHER2-ve subgroup (r = 0.24; P = 0.0023) and confirmed in this subgroup in 1,139 TransATAC tumours (r = 0.25; P < 0.0001). The positive relation extended to IHC-detected ER in ABC: mean ± 95% confidence interval (CI) H-scores were 90 ± 19 and 134 ± 19 for 0 and 1+ HER2 IHC categories, respectively (P = 0.0013). A trend toward lower relapse-free survival (RFS) was observed in patients with the lowest levels of ER and HER2 RNA levels within the ER+veHER2-ve subgroup both for ABC and TransATAC cohorts.Conclusions: ER and HER2 expression is positively correlated in HER2-ve tumors. The distinction between HER2+ve and HER2-ve is greater in ER-ve than in ER+ve tumors. These findings are important to consider in clinical trials of anti-HER2 and anti-endocrine therapy in HER2-ve disease. Trial Registration: Clinical trial identifier: ISRCTN31514446.
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- 2012
6. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials
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EARLY BREAST CANCER TRIALISTS' COLLABORATIVE GROUP (EBCTCG), Darby, S., Mcgale, P., Correa, C., Taylor, C., Arriagada, R., Clarke, M., Cutter, D., Davies, C., Ewertz, M., Godwin, J., Gray, R., Pierce, L., Whelan, T., Wang, Y., Peto, R., Albain, K, Anderson, S, Arriagada, R, Barlow, W, Bergh, J, Bliss, J, Buyse, M, Cameron, D, Carrasco, E, Clarke, M, Correa, C, Coates, A, Collins, R, Costantino, J, Cutter, D, Cuzick, J, Darby, S, Davidson, N, Davies, C, Davies, K, Delmestri, A, Di Leo, A, Dowsett, M, Elphinstone, P, Evans, V, Ewertz, M, Gelber, R, Gettins, L, Geyer, C, Goldhirsch, A, Godwin, J, Gray, R, Gregory, C, Hayes, D, Hill, C, Ingle, J, Jakesz, R, James, S, Kaufmann, M, Kerr, A, Mackinnon, E, Mcgale, P, Mchugh, T, Norton, L, Ohashi, Y, Paik, S, Pan, Hc, Perez, E, Peto, R, Piccart, M, Pierce, L, Pritchard, K, Pruneri, G, Raina, V, Ravdin, P, Robertson, J, Rutgers, E, Shao, Yf, Swain, S, Taylor, C, Valagussa, P, Viale, G, Whelan, T, Winer, E, Wang, Y, Wood, W, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Masuda, H, Nomura, Y, Sakai, K, Sugimachi, K, Toi, M, Tominaga, T, Uchino, J, Yoshida, M, Haybittle, Jl, Leonard, Cf, Calais, G, Geraud, P, Collett, V, Sayer, J, Harvey, Vj, Holdaway, Im, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Gnant, M, Greil, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, Cf, Steger, Gg, Stöger, H, Canney, P, Yosef, Hm, Focan, C, Peek, U, Oates, Gd, Powell, J, Durand, M, Mauriac, L, Dolci, S, Larsimont, D, Nogaret, Jm, Philippson, C, Piccart, Mj, Masood, Mb, Parker, D, Price, Jj, Lindsay, Ma, Mackey, J, Martin, M, Hupperets, Ps, Bates, T, Blamey, Rw, Chetty, U, Ellis, Io, Mallon, E, Morgan, Da, Patnick, J, Pinder, S, Olivotto, I, Ragaz, J, Berry, D, Broadwater, G, Cirrincione, C, Muss, H, Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Bowden, S, Brookes, C, Dunn, J, Fernando, I, Lee, M, Poole, C, Rea, D, Spooner, D, Barrett-Lee, Pj, Mansel, Re, Monypenny, Ij, Gordon, Nh, Davis, Hl, Lehingue, Y, Romestaing, P, Dubois, Jb, Delozier, T, Griffon, B, Mace Lesec'h, J, Rambert, P, Mustacchi, G, Petruzelka, Pribylova, O, Owen, Jr, Harbeck, N, Jänicke, F, Meisner, C, Schmitt, M, Thomssen, C, Meier, P, Shan, Y, Wang, X, Zhao, Db, Chen, Zm, Howell, A, Swindell, R, Burrett, Ja, Hermans, D, Hicks, C, Lay, M, Albano, J, de Oliveira CF, Gervásio, H, Gordilho, J, Johansen, H, Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, C, Shapiro, Cl, Christiansen, P, Ejlertsen, B, Jensen, Mb, Møller, S, Carstensen, B, Palshof, T, Trampisch, Hj, Dalesio, O, de Vries EG, Rodenhuis, S, van Tinteren, H, Comis, Rl, Davidson, Ne, Robert, N, Sledge, G, Solin, Lj, Sparano, Ja, Tormey, Dc, Dixon, Jm, Forrest, P, Jack, W, Kunkler, I, Rossbach, J, Klijn, Jg, Treurniet-Donker, Ad, van Putten WL, Rotmensz, N, Veronesi, U, Bartelink, H, Bijker, N, Bogaerts, J, Cardoso, F, Cufer, T, Julien, Jp, van de Velde CJ, Cunningham, Mp, Huovinen, R, Joensuu, H, Costa, A, Tinterri, C, Bonadonna, G, Gianni, L, Goldstein, Lj, Bonneterre, J, Fargeot, P, Fumoleau, P, Kerbrat, P, Luporsi, E, Namer, M, Eiermann, W, Hilfrich, J, Jonat, W, Kreienberg, R, Schumacher, M, Bastert, G, Rauschecker, H, Sauer, R, Sauerbrei, W, Schauer, A, Blohmer, Ju, Costa, Sd, Eidtmann, H, Gerber, G, Jackisch, C, Loibl, S, von Minckwitz, G, de Schryver, A, Vakaet, L, Belfiglio, M, Nicolucci, A, Pellegrini, F, Pirozzoli, Mc, Sacco, M, Valentini, M, Mcardle, Cs, Smith, Dc, Stallard, S, Dent, Dm, Gudgeon, Ca, Hacking, A, Murray, E, Panieri, E, Werner, Id, Segui, Ma, Galligioni, E, Lopez, M, Erazo, A, Medina, Jy, Horiguchi, J, Takei, H, Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D, Scheurlen, H, Sohn, Hc, Untch, M, Dafni, U, Markopoulos, C, Dafni, D, Fountzilas, G, Mavroudis, D, Klefstrom, P, Saarto, T, Gallen, M, Margreiter, R, de Lafontan, B, Mihura, J, Roché, H, Asselain, B, Salmon, Rj, Vilcoq, Jr, Bourgier, C, Koscielny, S, Laplanche, A, Lê, Mg, Spielmann, M, A'Hern, R, Ellis, P, Kilburn, L, Yarnold, Jr, Benraadt, J, Kooi, M, van de Velde AO, van Dongen JA, Vermorken, Jb, Castiglione, M, Colleoni, M, Collins, J, Forbes, J, Gelber, Rd, Lindtner, J, Price, Kn, Regan, Mm, Rudenstam, Cm, Senn, Hj, Thuerlimann, B, Bliss, Jm, Chilvers, Ce, Coombes, Rc, Hall, E, Marty, M, Possinger, K, Schmid, P, Wallwiener, D, Foster, L, George, Wd, Stewart, Hj, Stroner, P, Borovik, R, Hayat, H, Inbar, Mj, Robinson, E, Bruzzi, P, Del Mastro, L, Pronzato, P, Sertoli, Mr, Venturini, M, Camerini, T, De Palo, G, Di Mauro MG, Formelli, F, Amadori, D, Martoni, A, Pannuti, F, Camisa, R, Cocconi, G, Colozza, A, Passalacqua, R, Aogi, K, Takashima, S, Ikeda, T, Inokuchi, K, Sawa, K, Sonoo, H, Korzeniowski, S, Skolyszewski, J, Ogawa, M, Yamashita, J, Bastiaannet, E, van de Water, W, van Nes JG, Christiaens, R, Neven, P, Paridaens, R, Van den Bogaert, W, Braun, S, Janni, W, Martin, P, Romain, S, Janauer, M, Seifert, M, Sevelda, P, Zielinski, Cc, Hakes, T, Hudis, Ca, Wittes, R, Giokas, G, Kondylis, D, Lissaios, B, de la Huerta, R, Sainz, Mg, Altemus, R, Camphausen, K, Cowan, K, Danforth, D, Lichter, A, Lippman, M, O'Shaughnessy, J, Pierce, Lj, Steinberg, S, Venzon, D, Zujewski, Ja, D'Amico, C, Lioce, M, Paradiso, A, Chapman, Ja, Gelmon, K, Goss, Pe, Levine, Mn, Meyer, R, Parulekar, W, Pater, Jl, Pritchard, Ki, Shepherd, Le, Tu, D, Ohno, S, Anderson, A, Bass, G, Brown, A, Bryant, J, Dignam, J, Fisher, B, Mamounas, Ep, Redmond, C, Wickerham, L, Wolmark, N, Baum, M, Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Emdin, S, Jonsson, H, Lythgoe, Jp, Kissin, M, Erikstein, B, Hannisdal, E, Jacobsen, Ab, Varhaug, Je, Gundersen, S, Hauer-Jensen, M, Høst, H, Nissen-Meyer, R, Mitchell, Ak, Robertson, Jf, Ueo, H, Di Palma, M, Mathé, G, Misset, Jl, Levine, M, Morimoto, K, Takatsuka, Y, Crossley, E, Harris, A, Talbot, D, Taylor, M, Martin, Al, di Blasio, B, Ivanov, V, Paltuev, R, Semiglazov, V, Brockschmidt, J, Cooper, Mr, Falkson, Ci, Ashley, S, Makris, A, Powles, Tj, Smith, Ie, Gazet, Jc, Browne, L, Graham, P, Corcoran, N, Deshpande, N, di Martino, L, Douglas, P, Lindtner, A, Notter, G, Bryant, Aj, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Anderson, H, Killander, F, Malmström, P, Rydén, L, Arnesson, Lg, Carstensen, J, Dufmats, M, Fohlin, H, Nordenskjöld, B, Söderberg, M, Carpenter, Jt, Murray, N, Royle, Gt, Simmonds, Pd, Crowley, J, Gralow, J, Green, S, Hortobagyi, G, Livingston, R, Martino, S, Osborne, Ck, Adolfsson, J, Bondesson, T, Celebioglu, F, Dahlberg, K, Fornander, T, Fredriksson, I, Frisell, J, Göransson, E, Iiristo, M, Johansson, U, Lenner, E, Löfgren, L, Nikolaidis, P, Perbeck, L, Rotstein, S, Sandelin, K, Skoog, L, Svane, G, af Trampe, E, Wadström, C, Maibach, R, Thürlimann, B, Hakama, M, Holli, K, Isola, J, Rouhento, K, Saaristo, R, Brenner, H, Hercbergs, A, Yoshimoto, M, Paterson, Ah, Fyles, A, Meakin, Jw, Panzarella, T, Bahi, J, Reid, M, Spittle, M, Bishop, H, Bundred, Nj, Forsyth, S, Pinder, Se, Sestak, I, Deutsch, Gp, Kwong, Dl, Pai, Vr, Senanayake, F, Boccardo, F, Rubagotti, A, Hackshaw, A, Houghton, J, Ledermann, J, Monson, K, Tobias, Js, Carlomagno, C, De Laurentiis, M, De Placido, S, Williams, L, Broglio, K, Buzdar, Au, Love, Rr, Ahlgren, J, Garmo, H, Holmberg, L, Liljegren, G, Lindman, H, Wärnberg, F, Asmar, L, Jones, Se, Gluz, O, Liedtke, C, Nitz, U, Litton, A, Wallgren, A, Karlsson, P, Linderholm, Bk, Chlebowski, Rt, Caffier, H, Mcgale, P, Correa, C, Taylor, C, Arriagada, R, Clarke, M, Cutter, D, Davies, C, Ewertz, M, Godwin, J, Gray, R, Pierce, L, Whelan, T, Wang, Y, Peto, R, Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, DE PLACIDO, Sabino, Carlomagno, Chiara, Darby, S, McGale, P, Interne Geneeskunde, RS: GROW - School for Oncology and Reproduction, Other departments, CCA -Cancer Center Amsterdam, and Radiotherapy
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Oncology ,medicine.medical_specialty ,Neoplasm Recurrence, Local - epidemiology ,medicine.medical_treatment ,Population ,Breast Neoplasms ,Mastectomy, Segmental ,Breast cancer ,breast cancer ,Internal medicine ,medicine ,Breast-conserving surgery ,Humans ,education ,skin and connective tissue diseases ,radiotherapy ,Randomized Controlled Trials as Topic ,education.field_of_study ,business.industry ,Estrogen Antagonists - therapeutic use ,Mortality rate ,Age Factors ,Estrogen Antagonists ,General Medicine ,Breast Neoplasms - mortality - therapy ,medicine.disease ,Surgery ,Unilateral Breast Neoplasms ,Radiation therapy ,Clinical trial ,meta-analysis ,Tamoxifen ,Receptors, Estrogen ,Lymphatic Metastasis ,Female ,Radiotherapy, Adjuvant ,Neoplasm Grading ,Neoplasm Recurrence, Local ,business ,Mastectomy - Abstract
BACKGROUND: After breast-conserving surgery, radiotherapy reduces recurrence and breast cancer death, but it may do so more for some groups of women than for others. We describe the absolute magnitude of these reductions according to various prognostic and other patient characteristics, and relate the absolute reduction in 15-year risk of breast cancer death to the absolute reduction in 10-year recurrence risk. METHODS: We undertook a meta-analysis of individual patient data for 10,801 women in 17 randomised trials of radiotherapy versus no radiotherapy after breast-conserving surgery, 8337 of whom had pathologically confirmed node-negative (pN0) or node-positive (pN+) disease. FINDINGS: Overall, radiotherapy reduced the 10-year risk of any (ie, locoregional or distant) first recurrence from 35.0% to 19.3% (absolute reduction 15.7%, 95% CI 13.7-17.7, 2p/=20%), intermediate (10-19%), or lower (, link_to_OA_fulltext
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- 2011
7. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
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EBCTCG, Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Masuda, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Haybittle, Jl, Davies, C., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Forbes, Jf, Wilcken, N., Gnant, M., Jakesz, R., Ploner, M., Yosef, Hma, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Durand, M., Mauriac, L., Di Leo, A., Dolci, S., Piccart, Mj, Masood, Mb, Parker, D., Price, Jj, Hupperets, Psgj, Jackson, S., Ragaz, J., Berry, D., Broadwater, G., Cirrincione, C., Muss, H., Norton, L., Weiss, Rb, Abu-Zahra, Ht, Portnoj, Sm, Baum, M., Cuzick, J., Houghton, J., Riley, D., Gordon, Nh, Davis, Hl, Beatrice, A., Mihura, J., Naja, A., Lehingue, Y., Romestaing, P., Dubois, Jb, Delozier, T., Mace-Lesec H, J., Rambert, P., Andrysek, O., Barkmanova, J., Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Alison, R., Boreham, J., Clarke, M., Collins, R., Darby, S., Elphinstone, P., Evans, V., Godwin, J., Gray, R., Harwood, C., Hicks, C., James, S., Mackinnon, E., Mcgale, P., Mchugh, T., Mead, G., Peto, R., Wang, Y., Albano, J., Oliveira, Cf, Gervasio, H., Gordilho, J., Johansen, H., Mouridsen, Ht, Gelman, Rs, Harris, Jr, Henderson, Ic, Shapiro, Cl, Andersen, Kw, Axelsson, Ck, Blichert-Toft, M., Moller, S., Overgaard, J., Overgaard, M., Rose, C., Cartensen, B., Palshof, T., Trampisch, Hj, Dalesio, O., Vries, Ege, Rodenhuis, S., Tinteren, H., Comis, Rl, Davidson, Ne, Robert, N., Sledge, G., Tormey, Dc, Wood, W., Cameron, D., Chetty, U., Forrest, P., Jack, W., Rossbach, J., Klijn, Jgm, Treurniet-Donker, Ad, Putten, Wlj, Costa, A., Veronesi, U., Bartelink, H., Duchateau, L., Legrand, C., Sylvester, R., Hage, Ja, Velde, Cjh, Cunningham, Mp, Catalano, R., Creech, Rh, Bonneterre, J., Fargeot, P., Fumoleau, P., Kerbrat, P., Namer, M., Jonat, W., Kaufmann, M., Schumacher, M., Minckwitz, G., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schryver, A., Vakaet, L., Belfiglio, M., Nicolucci, A., Pellegrini, F., Sacco, M., Valentini, M., Mcardle, Cs, Smith, Dc, Galligioni, E., Boccardo, F., Rubagotti, A., Dent, Dm, Gudgeon, Ca, Hacking, A., Erazo, A., Medina, Jy, Izuo, M., Morishita, Y., Takei, H., Fentiman, Is, Hayward, Jl, Rubens, Rd, Skilton, D., Graeff, H., Janicke, F., Meisner, C., Scheurlen, H., Fournier, D., Dafni, U., Fountzilas, G., Klefstrom, P., Blomqvist, C., Saarto, T., Margreiter, R., Asselain, B., Salmon, Rj, Vilcoq, Jr, Rodrigo Arriagada, Hill, C., Laplanche, A., Le, Mg, Spielmann, M., Bruzzi, P., Montanaro, E., Rosso, R., Sertoli, MR, Venturini, M., Amadori, D., Benraadt, J., Kooi, M., Velde, Ao, Dongen, Ja, Vermorken, Jb, Castiglione, M., Cavalli, F., Coates, A., Collins, J., Forbes, J., Gelber, Rd, Goldhirsch, A., Lindtner, J., Price, Kn, Rudenstam, Cm, Senn, Hj, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Hall, E., Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Bonadonna, G., Camerini, T., Palo, G., Del Vecchio, M., Formelli, F., Valagussa, P., Martoni, A., Pannuti, F., Cocconi, G., Colozza, A., Camisa, R., Aogi, K., Takashima, S., Ikeda, T., Inokuchi, K., Sawa, K., Sonoo, H., Korzeniowski, S., Skolyszewski, J., Ogawa, M., Yamashita, J., Bonte, J., Christiaens, R., Paridaens, R., Den Boegart, W., Martin, P., Romain, S., Hakes, T., Hudis, Ca, Wittes, R., Giokas, G., Kondylis, D., Lissaios, B., La Huerta, R., Sainz, Mg, Altemus, R., Cowan, K., Danforth, D., Lichter, A., Lippman, M., O Shaughnessy, J., Pierce, Lj, Steinberg, S., Venzon, D., Zujewski, J., Paradiso, A., Lena, M., Schittulli, F., Myles, Jd, Pater, Jl, Pritchard, Ki, Anderson, S., Bass, G., Brown, A., Bryant, J., Costantino, J., Dignam, J., Fisher, B., Redmond, C., Wieand, S., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Jonsson, H., Larsson, Lg, Lythgoe, Jp, Kissin, M., Erikstein, B., Hannisdal, E., Jacobsen, Ab, Varhaug, Je, Gundersen, S., Hauer-Jensen, M., Host, H., Nissen-Meyer, R., Blamey, Rw, Mitchell, Ak, Morgan, Dal, Robertson, Jfr, Di Palma, M., Mathe, G., Misset, Jl, Clark, Rm, Levine, M., Morimoto, K., Takatsuka, Y., Crossley, E., Harris, A., Talbot, D., Taylor, M., Di Blasio, B., Ivanov, V., Semiglazov, V., Brockschmidt, J., Cooper, MR, Ueo, H., Falkson, Ci, A Hern, R., Ashley, S., Powles, Tj, Smith, Ie, Yarnold, Jr, Gazet, Jc, Cocoran, N., Deshpande, N., Di Martino, L., Douglas, P., Lindtner, A., Notter, G., Bryant, Ajs, Ewing, Gh, Firth, La, Krushen-Kosloski, Jl, Foster, L., George, Wd, Stewart, Hj, Stroner, P., Malmstrom, P., Moller, Tr, Ryden, S., Tengrup, I., Tennvall-Nittby, L., Carstenssen, J., Dufmats, M., Hatschek, T., Nordenskjold, B., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Martino, S., Osborne, Ck, Ravdin, Pm, Glas, U., Johansson, U., Rutqvist, Le, Singnomklao, T., Wallgren, A., Maibach, R., Thurlimann, B., Brenner, H., Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, Ahg, Meakin, Jw, Panzarella, T., Shan, Y., Shao, Yf, Wang, X., Zhao, Db, Chen, Zm, Pan, Hc, Bahi, J., Reid, M., Spittle, M., Deutsch, Gp, Senanayake, F., Kwong, Dlw, Bianco, Ar, Carlomagno, C., Laurentiis, M., Placido, S., Buzdar, Au, Smith, T., Bergh, J., Holmberg, L., Liljegren, G., Nilsson, J., Seifert, M., Sevelda, P., Zielinsky, Cc, Buchanan, Rb, Cross, M., Royle, Gt, Dunn, Ja, Hills, Rk, Lee, M., Morrison, Jm, Spooner, D., Litton, A., Chlebowski, Rt, Caffier, H., Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Early Breast Cancer Trialists' Collaborative, Group, DE LAURENTIIS, Michelino, and DE PLACIDO, Sabino
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Oncology ,medicine.medical_specialty ,Antineoplastic Agents, Hormonal ,DEATHS ,Ovariectomy ,Antineoplastic Agents ,Breast Neoplasms ,Aged ,Anthracyclines ,Antineoplastic Combined Chemotherapy Protocols ,Cause of Death ,Chemotherapy, Adjuvant ,Female ,Humans ,Middle Aged ,Neoplasm Metastasis ,Neoplasm Recurrence, Local ,Ovary ,Randomized Controlled Trials as Topic ,Receptors, Estrogen ,Survival Rate ,Tamoxifen ,Medicine (all) ,Breast cancer ,MammaPrint ,Internal medicine ,Receptors ,medicine ,Chemotherapy ,TAMOXIFEN ,skin and connective tissue diseases ,Survival rate ,Adjuvant ,Gynecology ,Hormonal ,medicine.diagnostic_test ,Oncotype DX Breast Cancer Assay ,business.industry ,General Medicine ,medicine.disease ,Estrogen ,Neoplasm Recurrence ,Local ,Hormonal therapy ,Oncotype DX ,business ,medicine.drug ,Epirubicin - Abstract
Background Quinquennial overviews (1985–2000) of the randomised trials in early breast cancer have assessed the 5 year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxorubicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modern aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50–69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0·0001 for recurrence, 2p For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age ( These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1–2 years of tamoxifen versus none (33 000); and about 5 years versus 1–2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- 2005
8. Distribution of doxorubicin to normal breast and tumour tissue in patients undergoing mastectomy
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Stallard S, Stan B. Kaye, George Wd, and J.G. Morrison
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Adult ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Mammary gland ,Breast Neoplasms ,Toxicology ,Breast cancer ,Pharmacokinetics ,Internal medicine ,Medicine ,Cytotoxic T cell ,Distribution (pharmacology) ,Humans ,Pharmacology (medical) ,Doxorubicin ,Tissue Distribution ,Breast ,Mastectomy ,Aged ,Pharmacology ,business.industry ,Cell cycle ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Oncology ,Microscopy, Fluorescence ,Female ,business ,medicine.drug - Abstract
Response to cytotoxic agents is assumed to be related to the concentration of drug achieved within tumour tissue. It is also often assumed that, given similar tissue concentrations of drug, normal tissues are less responsive to the same cytotoxic agents. This can partly be explained by the number of cells in normal tissues that are differentiated. These non dividing cells, in a stable testing phase of the cell cycle (G0) are less susceptible to cytotoxic damage. Little is actually known about the relationship between tumour drug concentrations and those in the tissue of the tumour-bearing organ. In this study, we compared doxorubicin concentrations in paired samples of tumour and normal breast tissue from 17 previously untreated women undergoing mastectomy. The relative cellularities of both specimens were estimated by measuring their DNA content. There was wide variation in intra-tumoural doxorubicin concentrations (range, 220-1,590 ng/g). Normal tissue also showed marked inter-patient variation (range, 81-1,000 ng/g). For a single patient the tumour drug concentrations were significantly higher than those in normal breast tissue (P less than 0.05), and tumour: normal tissue ratios ranged from 1.27 to 8.30. Where doxorubicin concentration was expressed in terms of the relative cellularity of the tissues, there was no significant difference between, drug concentrations in the tumour and those in normal breast tissue (tumour: normal ratios, 1.1:1.8). There was a significant correlation (r = 0.76, P less than 0.05) between peak serum values and tumour concentrations of drug. No correlation was found between drug concentrations achieved and the histological grade or oestrogen receptor status of the breast cancer.
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- 1990
9. Radiotherapy and tamoxifen in women with completely excided ductal carcinoma in suit
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George, WD, primary, Houghton, J, additional, Ellis, I, additional, Fentiman, IS, additional, and Spittle, M, additional
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- 2003
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10. Putative markers for the detection of breast carcinoma cells in blood
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Eltahir, EM, primary, Mallinson, DS, additional, Birnie, GD, additional, Hagan, C, additional, George, WD, additional, and Purushotham, AD, additional
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- 1998
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11. Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer
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Stanton, PD, primary, Cooke, TG, additional, Oakes, SJ, additional, Winstanley, J, additional, Holt, S, additional, George, WD, additional, and Murray, GD, additional
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- 1992
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12. C-erbB-2 expression and its importance in post menopausal patients
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Winstanley, JHR, primary, Cooke, TG, additional, Murray, GD, additional, Platt-Higgins, AM, additional, George, WD, additional, Holt, SM, additional, Myskov, M, additional, Spedding, A, additional, Barraclough, R, additional, and Rudland, PS, additional
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- 1992
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13. Enhancement of pulmonary tumour seeding by human coagulation factors II, IX, X – an investigation into the possible mechanisms involved
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Purushotham, AD, primary, McCulloch, P, additional, and George, WD, additional
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- 1991
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14. The long term prognostic significance of oestrogen receptor analysis in early carcinoma of the breast
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Winstanley, J, primary, Cooke, T, additional, George, WD, additional, Murray, G, additional, Holt, S, additional, Croton, R, additional, Griffiths, K, additional, and Nicholson, R, additional
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- 1991
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15. The long term prognostic significance of c-erbB-2 in primary breast cancer
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Winstanley, J, primary, Cooke, T, additional, Murray, GD, additional, Platt-Higgins, A, additional, George, WD, additional, Holt, S, additional, Myskov, M, additional, Spedding, A, additional, Barraclough, BR, additional, and Rudland, PS, additional
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- 1991
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16. Flow cytometric analysis of tumour infiltrating lymphocytes in breast cancer
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Whitford, P, primary, Mallon, EA, additional, George, WD, additional, and Campbell, AM, additional
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- 1990
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17. Flow cytometric analysis of cell surface carbohydrates in metastatic human breast cancer
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Alam, SM, primary, Whitford, P, additional, Cushley, W, additional, George, WD, additional, and Campbell, AM, additional
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- 1990
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18. Warfarin inhibits metastasis of Mtln3 rat mammary carcinoma without affecting primary tumour growth.
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McCulloch, P and George, WD
- Published
- 1989
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19. Promotion of metastasis by a specific complex of coagulation factors may be independent of fibrin formation.
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McCulloch, P and George, WD
- Published
- 1988
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20. Characterization of extensive genetic alterations in ductal carcinoma in situ by fluorescence in situ hybridization and molecular analysis.
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Murphy DS, Hoare SF, Going JJ, Mallon EE, George WD, Kaye SB, Brown R, Black DM, Keith WN, Murphy, D S, Hoare, S F, Going, J J, Mallon, E E, George, W D, Kaye, S B, Brown, R, Black, D M, and Keith, W N
- Abstract
Background: The molecular genetic analysis of invasive breast cancer has identified breast cancer as a genetically complex disease. Ductal carcinoma in situ (DCIS) is thought to represent a preinvasive step in breast cancer progression, yet we know little about its biologic behavior or the genetic alterations present. Because of the increasing diagnosis of DCIS by mammography screening and the debate over how DCIS should be managed, there is a clear need to define the molecular events underlying the development of DCIS.Purpose: Our purpose was to identify patterns of genetic alterations in DCIS.Methods: A group of 30 formalin-fixed, paraffin-embedded blocks of tissue collected from 1987 through 1989 from 21 patients with DCIS was studied. Chromosomal imbalances were determined by interphase cytogenetic analysis using the fluorescence in situ hybridization (FISH) technique. DNA probes were used that recognize chromosome-specific repetitive sequence loci at the centromeres of chromosomes 1, 3, 4, 6, 7, 8, 9, 10, 11, 16, 17, and 18. FISH was also used to detect ERBB2 gene amplification in DCIS. To complement the FISH studies, microsatellite analysis of markers near the BRCA1 region of chromosome 17 was done on tissue microdissected from multiple areas of DCIS. Chromosomal imbalances were determined by comparisons of chromosomal indices (total number of hybridization spots per total number of nuclei counted) of normal and DCIS tissue, using the two-sided Mann-Whitney test.Results: Using FISH, we have identified patterns of DNA loss and gain of certain chromosome-specific centromeric markers in DCIS. We observed frequent gains of markers on chromosomes 3, 10, and 17 as well as loss of chromosome 18-specific centromeric sequences. ERBB2 gene amplification was detected in tumors from four of 15 patients studied and was clearly limited to the tumor cells within the ducts. Because of the availability of topologically distinct regions of tumors from individuals, we were able to show that paired tumor specimens from individuals share genetic alterations and also have unique ones, suggesting clonal diversity within tumors. The combination of FISH and microsatellite analyses suggested that alterations in chromosome 17 may be quite complex; three of five patients whose samples were analyzed had allelic imbalance at markers on the long arm of chromosome 17.Conclusions: FISH and microsatellite analyses are useful in detecting extensive genetic alterations in DCIS. Examinations of DCIS tissue using these techniques have identified chromosomes 1, 3, 10, 16, 17, and 18 as candidate sites worthy of immediate study.Implications: This approach may give direction to future research aimed at precisely mapping loci altered in DCIS and help in understanding the biologic events associated with tumor progression or recurrence. [ABSTRACT FROM AUTHOR]- Published
- 1995
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21. Randomised comparison of 5 years of adjuvant tamoxifen with continuous therapy for operable breast cancer. The Scottish Cancer Trials Breast Group.
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Stewart, HJ, Forrest, AP, Everington, D, McDonald, CC, Dewar, JA, Hawkins, RA, Prescott, RJ, George, WD, Stewart, H J, Forrest, A P, McDonald, C C, Dewar, J A, Hawkins, R A, Prescott, R J, and George, W D
- Published
- 1996
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22. Massachusetts Department of Public Health
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George Wk, Gordon Ft, George Wd, Fisher Rg, Smith Jp, and Baird Ee
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chemistry ,Tetany ,business.industry ,Anesthesia ,Hyperventilation ,Respiration ,medicine ,chemistry.chemical_element ,General Medicine ,medicine.symptom ,Calcium ,business - Published
- 1963
23. Radiotherapy for screen-detected ductal carcinoma in situ: indications and utilization in the United Kingdom – findings from the Sloane Project
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Dodwell, D, Clements, K, George, WD, Lawrence, G, and Bishop, H
- Published
- 2006
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24. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ.
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Zammit C, Yelland A, Deutsch G, Cunnick GH, Mokbel K, Yau T, Epstein RJ, Baroni G, Pedotti A, Orecchia R, George WD, Houghton J, Ellis I, Fentiman IS, Spittle M, Tjalma WAA, Yau, Thomas, and Epstein, Richard J
- Published
- 2003
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25. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Scottish Cancer Trials Breast Group.
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Forrest AP, Stewart HJ, Everington D, Prescott RJ, McArdle CS, Harnett AN, Smith DC, George WD, Scottish Cancer Trials Breast Group, Forrest, A P, Stewart, H J, Everington, D, Prescott, R J, McArdle, C S, Harnett, A N, Smith, D C, and George, W D
- Abstract
Background: To determine whether, when primary breast cancer is treated by local excision supported by systemic therapy appropriate to the oestrogen receptor status (ER) of the tumour, local radiotherapy can be avoided.Methods: We carried out a randomised controlled trial in 585 patients aged less than 70 years with primary breast cancers of 4 cm or less in size in four specialist units and seven other hospitals in Scotland. After local excision of the tumour (1 cm margin) and an axillary lymph-node clearance or sample, all patients received systemic therapy with oral tamoxifen 20 mg daily or six 3-weekly intravenous bolus injections of cyclophosphamide 600 mg, methotrexate 50 mg, and fluorouracil 600 mg per m2, depending upon the ER concentration in the primary tumour. Patients were then randomly allocated to postoperative radical radiotherapy (50 Gy to breast with boost to the tumour bed) or to no further local treatment. The median follow-up of living patients was 5.7 years. The primary analysis was by intention to treat but since some patients did not receive systemic therapy appropriate to their ER status, a subsidiary analysis was restricted to 464 patients in whom all details of the protocol had been observed.Findings: In the primary analysis survival was equal in the radiotherapy and non-radiotherapy groups (hazard ratio [HR] 0.98, 95% CI 0.67-1.44). Event-free survival showed an advantage in the irradiated patients (HR 0.54, 95% CI 0.39-0.74), largely due to fewer loco-regional relapses (HR 0.20, 95% CI 0.12-0.33). The relapse rate in the ipsilateral breast was 24.5% in the non-irradiated group and 5.8% following breast irradiation. The subsidiary analysis confirmed these findings and indicated the advantage of radiotherapy irrespective of ER concentration. There was a non-significant trend towards fewer distant metastases in the irradiated group.Interpretation: After local excision of a primary breast cancer, we conclude that radiotherapy to the residual breast tissue is advisable even when selective adjuvant systemic therapy is given. [ABSTRACT FROM AUTHOR]- Published
- 1996
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26. Necrotising fasciitis secondary to perforated rectal adenocarcinoma presenting as a thigh swelling.
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Evans WD, Winters C, and Amin E
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- Adenocarcinoma diagnosis, Adenocarcinoma surgery, Anti-Bacterial Agents therapeutic use, Diagnosis, Differential, Digital Rectal Examination, Fasciitis, Necrotizing drug therapy, Fasciitis, Necrotizing surgery, Fatal Outcome, Humans, Intestinal Perforation surgery, Male, Middle Aged, Rectal Neoplasms diagnosis, Rectal Neoplasms surgery, Adenocarcinoma complications, Edema etiology, Fasciitis, Necrotizing etiology, Intestinal Perforation etiology, Rectal Neoplasms complications, Thigh
- Abstract
A 62-year-old man was admitted to the medical admissions ward with right thigh pain presumed to be a deep vein thrombosis (DVT). Subsequent duplex ultrasonography excluded a DVT but noted the presence of a significant amount of subcutaneous gas. A plain film radiograph was performed with the same finding raising the possibility of necrotising fasciitis (NF). Only at this point was digital rectal examination performed revealing a large rectal mass oozing pus and blood. CT imaging showed thickening of the rectum consistent with a tumour with gas and fluid in the perirectal space extending to the anterolateral right femur. Despite aggressive debridement and treatment, the patient deteriorated and died 6 weeks later. This case should serve as a reminder to consider digital rectal examination and the occurrence of a rectal perforation in all patients who present with suspicious thigh swellings., (2015 BMJ Publishing Group Ltd.)
- Published
- 2015
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27. Relationship among eye and muzzle temperatures measured using digital infrared thermal imaging and vaginal and rectal temperatures in hair sheep and cattle.
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George WD, Godfrey RW, Ketring RC, Vinson MC, and Willard ST
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- Animals, Female, Infections diagnosis, Infections veterinary, Infrared Rays, Lactation physiology, Sensitivity and Specificity, Thermography methods, Thermometers veterinary, Wounds and Injuries diagnosis, Wounds and Injuries veterinary, Body Temperature physiology, Cattle physiology, Nose physiology, Ocular Physiological Phenomena, Rectum physiology, Sheep physiology, Thermography veterinary, Vagina physiology
- Abstract
Digital infrared thermal imaging (DITI) using a thermal camera has potential to be a useful tool for the production animal industry. Thermography has been used in both humans and a wide range of animal species to measure body temperature as a method to detect injury or inflammation. The objective of these experiments was to compare the temperature of the eye (EYE) or muzzle (MUZ) measured using DITI to vaginal (VT) and rectal temperature (RT) as measures of core body temperature in hair sheep and beef cattle. In Exp.1 EYE, VT and RT were measured in lactating, multiparous hair sheep ewes (St. Croix White, n = 10, and Dorper × St. Croix White, n = 10) in a non-febrile state 5 times over a 48-h period. Data loggers were used to measure VT and a digital veterinary thermometer was used to measure RT. There was a high correlation (P < 0.001) between VT and RT (r = 0.95), EYE and RT (r = 0.76) and EYE and VT (r = 0.77). In Exp. 2 EYE, MUZ, VT and RT were measured in multiparous, lactating ewes (St. Croix White, n = 2, and Barbados Blackbelly, n = 12) at -12, -1, 0, 1, 2, 3, 4, 6, 12, 24, 36, and 48 h after being administered lipopolysaccharide (LPS; n = 7; 0.2 µg/kg BW, i.v.) or saline (n = 7; 0.5 mL, i.v.). Data loggers were used to measure VT and a digital veterinary thermometer was used to measure RT. When data were combined across treatments (LPS and saline) there was a high correlation (P < 0.001) between VT and RT (r = 0.96), EYE and RT (r = 0.82), MUZ and RT (r = 0.72), and EYE and VT (r = 0.93). In Exp. 3 EYE, MUZ, VT and RT were measured in multiparous, non-lactating, pregnant Senepol cattle (n = 44) between 0900 and 1200 h on a single day. A digital veterinary thermometer was used to measure both VT and RT. There was a high correlation (P < 0.001) between VT and RT (r = 0.78), a moderate correlation (P < 0.001) between VT and EYE (r = 0.52), RT and EYE (r = 0.58) and EYE and MUZ (r = 0.48). There was no correlation (P > 0.10) between RT or VT and MUZ. The findings of these three studies indicate that temperature of the eye, measured using DITI, can be used as an indicator of core body temperature in hair sheep and beef cattle as an alternative to using vaginal or rectal temperature.
- Published
- 2014
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28. De-differentiation of papillary thyroid carcinoma into squamous cell carcinoma. A case of coexistence within an excised neck lesion.
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Evans WD
- Subjects
- Aged, 80 and over, Carcinoma, Papillary radiotherapy, Carcinoma, Papillary surgery, Carcinoma, Squamous Cell surgery, Cell Dedifferentiation, Fatal Outcome, Humans, Lymph Nodes surgery, Lymphatic Metastasis, Male, Neck Dissection, Neoplasm Recurrence, Local surgery, Thyroid Neoplasms radiotherapy, Thyroid Neoplasms surgery, Carcinoma, Papillary secondary, Carcinoma, Squamous Cell pathology, Lymph Nodes pathology, Neoplasm Recurrence, Local pathology, Thyroid Neoplasms pathology
- Abstract
An 80-year-old man with papillary thyroid carcinoma of the neck underwent surgery and radioiodide therapy. He presented 11 years later with a lesion adjudged from fine needle aspiration to be a squamous cell carcinoma (SCC). Histological analysis of the excised mass revealed a lymph node overwhelmed with papillary thyroid carcinoma and moderately differentiated SCC thought to have transformed from papillary cells. A very small number of similar transformations specifically involving the 'tall cell variant' of papillary carcinoma transforming to spindle cell carcinoma have been reported previously. This case report demonstrates clear images of this rare occurrence and briefly considers factors leading to de-differentiation. The clinician should consider possible transformation from papillary thyroid cancer in cases of SCC of the head and neck as this variation may be more aggressive.
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- 2012
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29. Ten-year follow-up of skin-sparing mastectomy followed by immediate breast reconstruction.
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Romics L Jr, Chew BK, Weiler-Mithoff E, Doughty JC, Brown IM, Stallard S, Wilson CR, Mallon EA, and George WD
- Subjects
- Adult, Aged, Epidemiologic Methods, Female, Humans, Middle Aged, Neoadjuvant Therapy methods, Neoplasm Recurrence, Local etiology, Treatment Outcome, Breast Neoplasms surgery, Carcinoma, Ductal, Breast surgery, Dermatologic Surgical Procedures, Mammaplasty methods, Mastectomy methods, Organ Sparing Treatments methods
- Abstract
Background: The oncological safety of skin-sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is debated owing to a presumed compromise in the completeness of mastectomy. Current evidence is poor as it is based mostly on short-term follow-up data from highly selected patients., Methods: A prospectively maintained institutional database was searched to identify patients who underwent SSM and IBR between 1995 and 2000. A retrospective review of medical records was carried out, including only patients with ductal carcinoma in situ and invasive breast cancer. During this time all patients treated with mastectomy were offered IBR regardless of tumour stage., Results: Follow-up data from 253 consecutive patients with IBR were reviewed. Patients with incomplete follow-up data and those undergoing SSM for recurrent disease following previous lumpectomy were disregarded, leaving 207 for analysis. Offering IBR to all women requiring mastectomy resulted in a large proportion of patients with advanced disease. During a median follow-up of 119 months, 17 (8·2 per cent) locoregional, six (2·9 per cent) local and 22 (10·6 per cent) distant recurrences were detected; the overall recurrence rate was 39 (18·8 per cent). Overall recurrence rate was associated with axillary lymph node metastasis (P = 0·009), higher stage (P < 0·001) and higher tumour grade (P = 0·031). The breast cancer-specific survival rate was 90·8 per cent (19 of 207 women died from recurrence)., Conclusion: Based on these long-term follow-up data, SSM combined with IBR is an oncologically safe treatment option regardless of tumour stage., (Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)
- Published
- 2012
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30. Effects of multidisciplinary team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 722 women.
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Kesson EM, Allardice GM, George WD, Burns HJ, and Morrison DS
- Subjects
- Adult, Aged, Aged, 80 and over, Cohort Studies, Confidence Intervals, Disease Management, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Neoplasm Invasiveness, Proportional Hazards Models, Retrospective Studies, Scotland, State Medicine, Breast Neoplasms diagnosis, Breast Neoplasms mortality, Breast Neoplasms pathology, Breast Neoplasms therapy, Interdisciplinary Communication, Oncology Service, Hospital organization & administration, Oncology Service, Hospital standards, Patient Care Team organization & administration, Patient Care Team standards, Women's Health Services organization & administration, Women's Health Services standards
- Abstract
Objectives: To describe the effect of multidisciplinary care on survival in women treated for breast cancer., Design: Retrospective, comparative, non-randomised, interventional cohort study., Setting: NHS hospitals, health boards in the west of Scotland, UK., Participants: 14,358 patients diagnosed with symptomatic invasive breast cancer between 1990 and 2000, residing in health board areas in the west of Scotland. 13,722 (95.6%) patients were eligible (excluding 16 diagnoses of inflammatory cancers and 620 diagnoses of breast cancer at death)., Intervention: In 1995, multidisciplinary team working was introduced in hospitals throughout one health board area (Greater Glasgow; intervention area), but not in other health board areas in the west of Scotland (non-intervention area)., Main Outcome Measures: Breast cancer specific mortality and all cause mortality., Results: Before the introduction of multidisciplinary care (analysed time period January 1990 to September 1995), breast cancer mortality was 11% higher in the intervention area than in the non-intervention area (hazard ratio adjusted for year of incidence, age at diagnosis, and deprivation, 1.11; 95% confidence interval 1.00 to 1.20). After multidisciplinary care was introduced (time period October 1995 to December 2000), breast cancer mortality was 18% lower in the intervention area than in the non-intervention area (0.82, 0.74 to 0.91). All cause mortality did not differ significantly between populations in the earlier period, but was 11% lower in the intervention area than in the non-interventional area in the later period (0.89, 0.82 to 0.97). Interrupted time series analyses showed a significant improvement in breast cancer survival in the intervention area in 1996, compared with the expected survival in the same year had the pre-intervention trend continued (P=0.004). This improvement was maintained after the intervention was introduced., Conclusion: Introduction of multidisciplinary care was associated with improved survival and reduced variation in survival among hospitals. Further analysis of clinical audit data for multidisciplinary care could identify which aspects of care are most associated with survival benefits.
- Published
- 2012
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31. Impact of national guidelines on family history breast cancer surveillance.
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Saldanha JD, Garrett RM, Snaddon L, Longmuir M, Bradshaw N, Watt C, George WD, Wilson CR, Doughty JC, Stallard S, Reid I, Murday V, and Davidson R
- Subjects
- Adult, Aged, Aged, 80 and over, Breast Neoplasms genetics, Female, Humans, Mammography, Medical History Taking, Middle Aged, Risk Assessment, Scotland, Unnecessary Procedures statistics & numerical data, Breast Neoplasms diagnosis, Early Detection of Cancer, Guideline Adherence statistics & numerical data, Practice Guidelines as Topic
- Abstract
The breast cancer risk of women already under family history surveillance was accurately assessed according to national guidelines in an attempt to rationalize the service. Women attending two breast units in Glasgow between November 2003 and February 2005 were included. One thousand and five women under annual surveillance were assessed and had their relatives diagnoses verified. Four hundred and ninety-seven women were at significantly increased risk and eligible for follow-up. Five hundred and eight (50%) women attending were not eligible for family history surveillance, and 498 (98%) of these women accepted discharge. In conclusion, national guidelines have helped to more clearly define women who should undergo surveillance. This avoids unnecessary and potentially harmful routine investigations, and the service has been improved.
- Published
- 2011
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32. Pancreatic-derived pathfinder cells enable regeneration of critically damaged adult pancreatic tissue and completely reverse streptozotocin-induced diabetes.
- Author
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Stevenson K, Chen D, MacIntyre A, McGlynn LM, Montague P, Charif R, Subramaniam M, George WD, Payne AP, Davies RW, Dorling A, and Shiels PG
- Subjects
- Adult, Animals, Diabetes Mellitus, Experimental pathology, Female, Humans, In Situ Hybridization, Fluorescence, Mice, Mice, Inbred C57BL, Pancreas pathology, Rats, Diabetes Mellitus, Experimental therapy, Pancreas cytology, Pancreas physiology, Regeneration, Stem Cell Transplantation
- Abstract
We demonstrate that intravenous delivery of human, or rat, pancreas-derived pathfinder (PDP) cells can totally regenerate critically damaged adult tissue and restore normal function across a species barrier. We have used a mouse model of streptozotocin (STZ)-induced diabetes to demonstrate this. Normoglycemia was restored and maintained for up to 89 days following the induction of diabetes and subsequent intravenous delivery of PDP cells. Normal pancreatic histology also appeared to be restored, and treated diabetic animals gained body weight. Regenerated tissue was primarily of host origin, with few rat or human cells detectable by fluorescent in situ hybridization (FISH). Crucially, the insulin produced by these animals was overwhelmingly murine in origin and was both types I and II, indicative of a process of developmental recapitulation. These results demonstrate the feasibility of using intravenous administration of adult cells to regenerate damaged tissue. Critically, they enhance our understanding of the mechanisms relating to such repair and suggest a means for novel therapeutic intervention in loss of tissue and organ function with age.
- Published
- 2011
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33. Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial.
- Author
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Cuzick J, Sestak I, Pinder SE, Ellis IO, Forsyth S, Bundred NJ, Forbes JF, Bishop H, Fentiman IS, and George WD
- Subjects
- Adult, Aged, Combined Modality Therapy, Female, Humans, Middle Aged, Breast Neoplasms therapy, Carcinoma, Intraductal, Noninfiltrating therapy, Estrogen Antagonists therapeutic use, Tamoxifen therapeutic use
- Abstract
Background: Initial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial., Methods: Women with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870., Findings: Between May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9-14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30-0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19-0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22-0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45-1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58-0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51-0·86; p=0·03) and contralateral tumours (0·44, 0·25-0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66-1·38; p=0·8). No data on adverse events except cause of death were collected for this trial., Interpretation: This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision., Funding: Cancer Research UK and the Australian National Health and Medical Research Council., (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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34. A new pathological system for grading DCIS with improved prediction of local recurrence: results from the UKCCCR/ANZ DCIS trial.
- Author
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Pinder SE, Duggan C, Ellis IO, Cuzick J, Forbes JF, Bishop H, Fentiman IS, and George WD
- Subjects
- Age Factors, Female, Humans, Inflammation complications, Multivariate Analysis, Randomized Controlled Trials as Topic, Breast Neoplasms pathology, Carcinoma in Situ pathology, Carcinoma, Ductal, Breast pathology, Neoplasm Recurrence, Local pathology
- Abstract
Background: There is no consensus agreement regarding optimal management of locally excised ductal carcinoma in situ (DCIS) or features of greatest assistance in predicting disease behaviour. Cases in the UKCCCR/ANZ DCIS trial have been histologically reviewed to determine the features of prognostic importance., Method: A total of 72% of 1694 cases entered into the UKCCCR/ANZ DCIS trial had full pathological review. A large number of histological features were assessed, blinded to outcome and compared regarding ability to predict ipsilateral recurrence, as either DCIS or progression to invasive carcinoma., Results: Pathological features associated with ipsilateral recurrence in univariate analysis included high cytonuclear grade, larger lesion size, growth pattern, presence of necrosis or chronic inflammation, incompleteness (or uncertainty of completeness) of excision and smaller margin width. Receipt of post-operative radiotherapy was also a strong prognostic factor.We report a novel sub-division of the large group of high-grade lesions, which enables identification of a very poor prognosis sub-group; namely, DCIS that is of high cytonuclear grade, predominantly (>50%) solid architecture, bearing extensive comedo-type necrosis (>50% of ducts). In addition, we found little difference in ipsilateral recurrence rates between low- and intermediate-grade groups. Hazard ratios for low, intermediate, high and the new, very high, grade were 0.42, 0.33, 0.62 and 1.00, respectively, for ipsilateral in situ or invasive recurrence., Conclusion: We present a novel pathological classification for DCIS with substantially better prognostic discrimination for ipsilateral recurrence than the classical categorisation based on cytonuclear grade alone.
- Published
- 2010
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35. Isolation, characterization, and differentiation of thy1.1-sorted pancreatic adult progenitor cell populations.
- Author
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Stevenson KS, McGlynn L, Hodge M, McLinden H, George WD, Davies RW, and Shiels PG
- Subjects
- Adult Stem Cells metabolism, Animals, Antigens, Surface genetics, Cell Membrane metabolism, Gene Expression Regulation, Glycogen metabolism, Immunohistochemistry, Liver cytology, Periodic Acid-Schiff Reaction, Rats, Reverse Transcriptase Polymerase Chain Reaction, Adult Stem Cells cytology, Antigens, Surface metabolism, Cell Differentiation, Cell Separation methods, Flow Cytometry methods, Pancreas cytology
- Abstract
We have isolated a novel progenitor cell population from adult rat pancreatic ducts, termed pancreatic-derived progenitor cells (PDPCs). Here, we report the in vitro culture, selection, and characterization of Thy1.1-positive and Thy1.1-negative PDPC subpopulations. These cells exhibit bipotentiality for differentiation into both pancreatic and hepatic cell types. Significantly, they express Pdx-1. Using a serum-free FGF-4-containing differentiation protocol, we have observed a time course of both morphological and gene expression changes indicative of hepatic lineage differentiation for the Thy1.1-positive subpopulation. These cells express albumin and store glycogen, typical features of mature hepatocytes. The Thy1.1-positive subpopulation could also readily be induced to differentiate into a pancreatic lineage with characteristic morphological changes resulting in three-dimensional islet-like structures and the transcriptional expression of insulin and glucagon in addition to Pdx-1. No morphological evidence of islet-like clusters was observed using the Thy1.1-negative population. However, Thy1.1-negative cells grown in pancreatic differentiation medium did show insulin gene transcription. Glucagon was not expressed in the undifferentiated Thy1.1-negative cells, nor was it induced in vitro after differentiation. The detection of Pdx-1 transcriptional expression in both populations indicates their potential as a novel source of non-beta-cell-derived insulin.
- Published
- 2009
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36. [Oncoplastic approach in breast cancer surgery--a new challenge for the future breast surgeon?].
- Author
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Romics L, Weiler-Mithoff E, Cooke TG, and George WD
- Subjects
- Female, Humans, Mastectomy, Modified Radical, Mastectomy, Segmental, Microsurgery, Vascular Surgical Procedures, Breast Neoplasms surgery, Mammaplasty methods, Surgical Flaps
- Abstract
The future challenge of breast surgery, the so-called oncoplastic approach is reviewed in this article. The authors discuss the most frequently applied surgical techniques as well as their indications. Medline and pubmed search was carried out using the following keywords and cross-references: "oncoplastic breast surgery", "breast reconstruction", "breast conserving surgery" and "reduction mammoplasty". Original and review papers published in English language and their references were included. In the literature surprisingly, a large variety of breast oncoplastic surgical procedures has been described. Although reconstructions with local flaps are relatively easy procedures, proper indications for these are critical in order to improve cosmesis after breast conservation. Applications of pedicled flaps are technically more demanding, and only properly trained oncoplastic breast or plastic surgeons are able to provide the possibly best aesthetic outcome after mastectomy or breast conserving surgery. Finally, carrying out free flap reconstructions after mastectomy should be assigned exclusively to plastic surgeons qualified in microsurgical techniques, and not to surgical oncologists. As conclusions oncoplastic approach will be an integral element of the surgical treatment of breast cancer in the future. Breast oncoplastic training is an interdisciplinary task, which combines surgical oncological management of breast cancers with aesthetic/reconstructive breast surgery.
- Published
- 2008
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37. Comparison of breast cancer mortality rates with those of ovarian and colorectal carcinoma.
- Author
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Stearns AT, Hole D, George WD, and Kingsmore DB
- Subjects
- Adult, Aged, Female, Humans, Middle Aged, Prospective Studies, Risk Factors, Scotland epidemiology, Survival Analysis, Survival Rate, Breast Neoplasms mortality, Colorectal Neoplasms mortality, Ovarian Neoplasms mortality
- Abstract
Background: Traditional survival curves cannot easily be used to predict outcome for an individual patient on a year-to-year basis. This difficulty is partly overcome by yearly mortality analysis. This method was employed to analyse long-term follow-up of three cancers: colorectal, ovarian and breast cancer., Methods: The study used prospectively collected cancer registry data from geographically defined regions in Scotland. Cohort sizes were 7196 patients with breast cancer, 3200 with colorectal cancer and 1866 with ovarian cancer. Follow-up extended to 23 years., Results: Two distinct patterns of mortality emerged. Mortality rates for ovarian and colorectal cancer were initially high (41 and 21 per cent) but decreased rapidly; by 10 years patients had either died or were cured. The influence of stage diminished with follow-up. Breast cancer mortality was lower than that of colorectal or ovarian cancer, but remained raised in comparison to the general population throughout follow-up. The influence of breast cancer size reduced with follow-up, whereas that of nodal status persisted., Conclusion: Patients with breast cancer live at increased risk of death to the end of follow-up, supporting the concept of dormancy in breast cancer biology. This was not observed with colorectal or ovarian cancer., (Copyright (c) 2007 British Journal of Surgery Society Ltd.)
- Published
- 2007
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38. Quantifying tumour-infiltrating lymphocyte subsets: a practical immuno-histochemical method.
- Author
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Loughlin PM, Cooke TG, George WD, Gray AJ, Stott DI, and Going JJ
- Subjects
- Algorithms, Antigens, CD20 analysis, CD3 Complex analysis, CD4 Antigens analysis, CD8 Antigens analysis, Calibration, Cell Count methods, Female, Humans, Image Interpretation, Computer-Assisted, Immunohistochemistry standards, Immunophenotyping methods, Pilot Projects, Reproducibility of Results, Software, Antigens, Neoplasm analysis, Breast Neoplasms immunology, Carcinoma, Ductal, Breast immunology, Immunohistochemistry methods, Lymphocyte Subsets immunology, Lymphocytes, Tumor-Infiltrating immunology
- Abstract
Background: Efficient histological quantification of tumour-infiltrating T and B lymphocyte (TIL) subsets in archival tissues would greatly facilitate investigations of the role of TIL in human cancer biology. We sought to develop such a method., Methods: Ten x40 digital images of 4 micro sections of 16 ductal invasive breast carcinomas immunostained for CD3, CD4, CD8, and CD20 were acquired (a total of 640 images). The number of pixels in each image matching a partition of Lab colour space corresponding to immunostained cells were counted using the 'Color range' and 'Histogram' tools in Adobe Photoshop 7. These pixel counts were converted to cell counts per mm(2) using a calibration factor derived from one, two, three or all 10 images of each case/antibody combination., Results: Variations in the number of labelled pixels per immunostained cell made individual calibration for each case/antibody combination necessary. Calibration based on two fields containing the most labelled pixels gave a cell count minimally higher (+5.3%) than the count based on 10-field calibration, with 95% confidence limits -14.7 to +25.3%. As TIL density could vary up to 100-fold between cases, this accuracy and precision are acceptable., Conclusion: The methodology described offers sufficient accuracy, precision and efficiency to quantify the density of TIL sub-populations in breast cancer using commonly available software, and could be adapted to batch processing of image files.
- Published
- 2007
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39. Altered sirtuin expression is associated with node-positive breast cancer.
- Author
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Ashraf N, Zino S, Macintyre A, Kingsmore D, Payne AP, George WD, and Shiels PG
- Subjects
- Analysis of Variance, Breast Neoplasms genetics, Carcinoma, Ductal, Breast genetics, Cell Line, Cell Line, Tumor, Cellular Senescence genetics, Cyclin-Dependent Kinase Inhibitor p16 genetics, Cyclin-Dependent Kinase Inhibitor p21 genetics, Gene Expression Regulation, Neoplastic, Humans, Lymphatic Metastasis, Prognosis, RNA, Neoplasm genetics, RNA, Neoplasm metabolism, Sirtuin 3, Breast Neoplasms pathology, Carcinoma, Ductal, Breast pathology, Mitochondrial Proteins genetics, Sirtuins genetics
- Abstract
Sirtuins are genes implicated in cellular and organismal ageing. Consequently, they are speculated to be involved in diseases of ageing including cancer. Various cancers with widely differing prognosis have been shown to have differing and characteristic expression of these genes; however, the relationship between sirtuin expression and cancer progression is unclear. In order to correlate cancer progression and sirtuin expression, we have assessed sirtuin expression as a function of primary cell ageing and compared sirtuin expression in normal, 'nonmalignant' breast biopsies to breast cancer biopsies using real-time polymerase chain reaction (PCR). Levels of SIRT7 expression were significantly increased in breast cancer (P<0.0001). Increased levels of SIRT3 and SIRT7 transcription were also associated with node-positive breast cancer (P<0.05 and P<0.0001, respectively). This study has demonstrated differential sirtuin expression between nonmalignant and malignant breast tissue, with consequent diagnostic and therapeutic implications.
- Published
- 2006
- Full Text
- View/download PDF
40. The use of telomere biology to identify and develop superior nitrone based anti-oxidants.
- Author
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Sklavounou E, Hay A, Ashraf N, Lamb K, Brown E, Mac Intyre A, George WD, Hartley RC, and Shiels PG
- Subjects
- Antioxidants chemistry, Bromodeoxyuridine metabolism, Cells, Cultured, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16 genetics, Cyclin-Dependent Kinase Inhibitor p21 genetics, DNA Helicases genetics, Dose-Response Relationship, Drug, Fibroblasts cytology, Fibroblasts drug effects, Fibroblasts metabolism, Gene Expression drug effects, Humans, Hydrogen Peroxide pharmacology, Infant, Newborn, Ku Autoantigen, Molecular Structure, Oxidants pharmacology, Reverse Transcriptase Polymerase Chain Reaction, Structure-Activity Relationship, Telomere genetics, Telomere metabolism, beta-Galactosidase metabolism, Antioxidants pharmacology, Drug Design, Nitrogen Oxides chemistry, Telomere drug effects
- Abstract
We have employed a biological chemistry approach to dissect the mechanisms underpinning cellular responses to oxidant stress and to develop biologically relevant anti-oxidants. We have used telomere biology to define cellular stress responses and have observed telomere independent, p21- and p16-dependent stasis following oxidative insult in human fibroblasts. This was accompanied by a [corrected] reduction in XRCC5 expression and a reduction in [corrected] SIRT 1 expression. Using these markers in conjunction with senescence-associated beta-galactosidase expression, we have developed and screened novel nitrone based anti-oxidant compounds. We have identified functional compounds that are unsuitable for use in primary human cells. This has allowed subsequent identification of suitably structured compounds that act as superior biological anti-oxidants, which have potential for use in clinical interventions.
- Published
- 2006
- Full Text
- View/download PDF
41. Inadequate treatment of symptomatic breast cancer.
- Author
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Kingsmore DB, Hole DJ, Gillis CR, and George WD
- Subjects
- Adult, Aged, Axilla, Breast Neoplasms mortality, Cohort Studies, Female, Humans, Lymph Node Excision methods, Lymph Node Excision mortality, Lymphatic Metastasis, Mastectomy methods, Mastectomy mortality, Middle Aged, Neoplasm Recurrence, Local etiology, Neoplasm Recurrence, Local mortality, Risk Factors, Scotland epidemiology, Survival Analysis, Treatment Outcome, Breast Neoplasms surgery, Quality of Health Care
- Abstract
Background: Early trials that compared breast and axillary treatments showed differing recurrence rates without significant differences in survival. Consequently, there was a wide range of opinion and practice in the management of breast cancer. The present study explored this variability in surgical management to determine the impact of breast and axillary treatment on recurrence and survival., Methods: The records of 2776 women with histologically confirmed invasive breast cancer diagnosed between 1986 and 1991 were reviewed. The relationship between adequacy of breast and axillary treatment, recurrence and survival was examined in 2122 women who had surgery with curative intent. A Cox proportional hazards model that included tumour size, node status, grade, socioeconomic status and use of adjuvant therapy was used., Results: Inadequate treatment was associated with a significantly higher risk of local recurrence after breast-conserving surgery (relative hazard ratio (RHR) 4.19 (95 per cent confidence interval (c.i.) 2.73 to 6.43); P < 0.001). Inadequate axillary treatment was associated with a significantly higher risk of regional recurrence (RHR 2.29 (95 per cent c.i. 1.65 to 3.16); P < 0.001). The risk of death from breast cancer was significantly higher if locoregional treatment was inadequate (RHR 1.29 (95 per cent c.i. 1.07 to 1.55); P = 0.008)., Conclusion: Adequate surgery is fundamental to the optimal treatment of breast cancer. Inadequate surgery resulted in higher recurrence rates despite adjuvant treatments.
- Published
- 2005
- Full Text
- View/download PDF
42. A 1-year prospective study of individual variation in distress, and illness perceptions, after treatment for breast cancer.
- Author
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Millar K, Purushotham AD, McLatchie E, George WD, and Murray GD
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Breast Neoplasms diagnosis, Breast Neoplasms surgery, Culture, Drainage, Female, Humans, Mastectomy psychology, Mastectomy, Segmental psychology, Personality Inventory, Prospective Studies, Stress, Psychological diagnosis, Stress, Psychological psychology, Surgical Flaps, Surveys and Questionnaires, Suture Techniques, Adaptation, Psychological, Breast Neoplasms psychology, Individuality, Sick Role, Stress, Psychological complications
- Abstract
Objective: The primary objective was to conduct a detailed analysis of individual variation in psychological morbidity in the year following surgery for breast cancer. The salience of the patients' "illness perceptions" to morbidity was examined as a secondary objective., Methods: Psychological morbidity was assessed with the General Health Questionnaire (GHQ-28) in a prospective study of 371 women having surgery for primary breast cancer. Patients also completed the Illness Perception Questionnaire (IPQ), Mental Adjustment to Cancer Scale (MAC) and the Eysenck Personality Scales (EPS). Assessments were made postoperatively and at 3, 6 and 12 months after surgery., Results: Whilst descriptive statistics indicated a general reduction in mean distress over the 12-month follow-up, close analysis showed that a quarter of all patients maintained clinically significant levels of distress throughout the period. Patients with chronically elevated distress were characterised by higher levels of neuroticism, greater symptom awareness, more pain and poorer self-rated general health. In the regression analysis, psychological morbidity across the 1-year follow-up was predicted principally by the immediate postoperative state of distress, IPQ symptom awareness and the perceived time line of the illness, general health and, to a more minor extent, by neuroticism., Conclusion: There is marked individual variation in psychological morbidity in the year following breast cancer surgery, which is reliably predicted by the patient's immediate postoperative state of distress, her perception of the impact of the symptoms and the time line of the disease. Subgroups of patients with chronically high distress are characterised by factors including personality and negative perceptions and beliefs about their illness.
- Published
- 2005
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- View/download PDF
43. Axillary recurrence in breast cancer.
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Kingsmore DB, Hole DJ, Gillis CR, and George WD
- Subjects
- Adult, Aged, Axilla, Breast Neoplasms therapy, Carcinoma, Ductal, Breast therapy, Female, Humans, Incidence, Lymphatic Metastasis, Middle Aged, Recurrence, Registries, Scotland epidemiology, Breast Neoplasms epidemiology, Breast Neoplasms pathology, Carcinoma, Ductal, Breast epidemiology, Carcinoma, Ductal, Breast secondary, Lymph Nodes pathology
- Abstract
Aim: To determine whether axillary recurrence reflects inadequate axillary treatment or adverse pathological features., Methods: The case-records were reviewed of 2122 women aged under 75 years, treated for invasive breast cancer during the time-period 1/1/86-31/12/91 in a geographically defined area. Data were abstracted on operations performed, pathological features, post-operative treatments and details of axillary recurrence. The risk of axillary recurrence was examined by pathological, treatment and patient factors., Results: Axillary recurrence was more than twice as likely after inadequate compared to adequate treatment of the axilla (adequate staging or axillary radiotherapy or clearance). Delayed treatment of the axilla was not as successful as adequate primary treatment: multiple axillary recurrences were twice as common, one third of which were uncontrolled at time of death. Inadequate surgical treatment was associated with increased rates of recurrence despite endocrine therapy, chemotherapy or radiotherapy. Lymphoedema was twice as common if axillary radiotherapy was combined with any axillary surgical procedure., Conclusions: Axillary recurrence is more common in tumours with adverse pathology but may also result from inadequate axillary treatment. In order to minimise axillary recurrence, optimal treatment of the axilla entails adequate staging (sampling of four or more nodes) and treatment (axillary clearance or radiotherapy and endocrine therapy) in all women.
- Published
- 2005
- Full Text
- View/download PDF
44. Does deprivation affect breast cancer management?
- Author
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Henley NC, Hole DJ, Kesson E, Burns HJ, George WD, and Cooke TG
- Subjects
- Adult, Aged, Analysis of Variance, Breast Neoplasms pathology, Breast Neoplasms radiotherapy, Breast Neoplasms surgery, Female, Humans, Logistic Models, Lymphatic Metastasis, Middle Aged, Predictive Value of Tests, Scotland, Breast Neoplasms therapy, Choice Behavior, Mastectomy methods, Socioeconomic Factors
- Abstract
We evaluated whether social deprivation affected decision-making for breast cancer surgery. Of 3419 patients, 53.6% had mastectomy and this was predicted by deprivation, age, tumour size and hospital, all of which retained significance on multivariate analysis, except deprivation. Pathological characteristics and surgical decision-making determined choice of operation not deprivation.
- Published
- 2005
- Full Text
- View/download PDF
45. Immediate breast reconstruction does not lead to a delay in the delivery of adjuvant chemotherapy.
- Author
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Wilson CR, Brown IM, Weiller-Mithoff E, George WD, and Doughty JC
- Subjects
- Chemotherapy, Adjuvant methods, Cohort Studies, Female, Humans, Mastectomy methods, Time Factors, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms surgery, Mammaplasty methods
- Abstract
Immediate breast reconstruction (IBR) has been considered by some to lead to a delay in the delivery of adjuvant chemotherapy. Our aim was to determine whether IBR led to a delay when compared to conservation surgery and non-reconstructive mastectomy. Ninety-five cases of IBR receiving chemotherapy were reviewed. These were compared to 95 consecutively treated patients undergoing conservation surgery and 95 undergoing non-reconstructive mastectomy. Our data shows that IBR does not lead to a delay in the delivery of adjuvant chemotherapy when compared to standard non-reconstructive surgery and should not adversely affect breast cancer outcome.
- Published
- 2004
- Full Text
- View/download PDF
46. The future of breast surgery: a new sub-speciality of oncoplastic breast surgeons?
- Author
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Brown IM, Wilson CR, Doughty JC, George WD, Cooke TG, Weiler-Mithoft EM, Scott JR, and Ray AK
- Subjects
- Female, Humans, United Kingdom, Breast Neoplasms surgery, Mastectomy trends, Medical Oncology trends
- Published
- 2004
- Full Text
- View/download PDF
47. Re: Inequalities in breast cancer reconstructive surgery according to social and locational status in Western Australia.
- Author
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Brown IM, Wilson CR, Doughty JC, Weiler-Mithoff EM, and George WD
- Subjects
- Data Collection, Female, Health Services Accessibility, Humans, Insurance, Health, Mastectomy, Medical Indigency, Western Australia, Breast Neoplasms surgery, Mammaplasty statistics & numerical data, Social Class
- Published
- 2003
- Full Text
- View/download PDF
48. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial.
- Author
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Houghton J, George WD, Cuzick J, Duggan C, Fentiman IS, and Spittle M
- Subjects
- Australia, Chemotherapy, Adjuvant, Female, Follow-Up Studies, Humans, Mastectomy, Segmental, Middle Aged, Neoplasm Recurrence, Local, New Zealand, Radiotherapy, Adjuvant, United Kingdom, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms therapy, Carcinoma in Situ therapy, Carcinoma, Ductal, Breast therapy, Tamoxifen therapeutic use
- Abstract
Background: As a consequence of mammographic breast screening programmes, ductal carcinoma in situ is diagnosed with increasing frequency. Mastectomy for localised ductal carcinoma in situ is thought to be an over-treatment by many physicians, but there is much controversy as to whether complete local excision alone is sufficient. We aimed to assess the effectiveness of adjuvant radiotherapy and tamoxifen., Methods: We used a 2x2 factorial design in a randomised controlled trial. Between May, 1990, and August, 1998, 1701 patients recruited from screening programmes were randomised to both treatments in combination or singly, or to none, or to either one (eg, radiotherapy) with an elective decision to give or to withhold the other (ie, in this case tamoxifen). Patients had complete surgical excision of the lesion confirmed by specimen radiography and histology. Patients have been followed up at least once a year. Median follow-up was 52.6 (range 2.4-118.3) months. Our primary endpoint was the incidence of ipsilateral invasive disease., Findings: Ipsilateral invasive disease was not reduced by tamoxifen but recurrence of overall ductal carcinoma in situ was decreased (hazard ratio 0.68 [0.49-0.96]; p=0.03). Radiotherapy reduced the incidence of ipsilateral invasive disease (0.45 [0.24-0.85]; p=0.01) and ipsilateral ductal carcinoma in situ (0.36 [0.19-0.66]; p=0.0004), but there was no effect on the occurrence of contralateral disease. There was no evidence of interaction between radiotherapy and tamoxifen., Interpretation: Radiotherapy can be recommended for patients with ductal carcinoma in situ treated by complete local excision; however, there is little evidence for the use of tamoxifen in these women.
- Published
- 2003
- Full Text
- View/download PDF
49. Increased mortality from breast cancer and inadequate axillary treatment.
- Author
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Kingsmore DB, Ssemwogerere A, Hole DJ, Gillis CR, and George WD
- Subjects
- Adult, Aged, Axilla, Female, Humans, Lymph Node Excision standards, Lymphatic Metastasis, Middle Aged, Neoplasm Staging, Radiotherapy, Adjuvant, Registries, Survival Analysis, Breast Neoplasms mortality, Breast Neoplasms pathology, Diagnostic Errors, Lymph Node Excision methods
- Abstract
Background: The assessment of axillary nodal status remains divisive: inaccurate staging may result in untreated axillary disease, and appropriate adjuvant therapy not being delivered. The impact of inadequate axillary treatment on survival remains controversial. We analyse the impact of failure to adequately assess the axillary nodal status on survival., Methods: All women with confirmed breast cancer in a 15-year period were identified, and the original pathology reports examined, and details of radiotherapy obtained. The survival of women by axillary sample size was compared to a reference group of women and corrected for nodal status, tumour size, age, deprivation category and speciality of treating surgeon., Findings: Sampling less than four nodes is associated with a significantly increased risk of death. This cannot be due to understaging the extent of axillary disease nor is fully explainable by differential prescription of adjuvant therapies. We conclude that the survival of the women studied may have been adversely effected by inadequate axillary treatment.
- Published
- 2003
- Full Text
- View/download PDF
50. Pregnancy postponement and childlessness leads to chronic hypervascularity of the breasts and cancer risk.
- Author
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Simpson HW, McArdle CS, George WD, Griffiths K, Turkes A, and Pauson AW
- Subjects
- Adult, Age Factors, Body Temperature, Breast Neoplasms etiology, Female, Humans, Menopause, Middle Aged, Regional Blood Flow, Risk Factors, Breast blood supply, Breast Neoplasms physiopathology, Neovascularization, Pathologic, Parity, Pregnancy physiology
- Abstract
Epidemiologists have established that women with small families, and particularly nulliparae, are prone to develop breast cancer later in life. We report that physiological mammary hypervascularity may be an intermediate reason against the background that breast-core vascularity is normal in pregnancy but pathological in the vascularisation of cancer. We examined breast 'core' vascularity in nulliparae during their potential reproductive life and in parous women after their last birth but before their menopause. Fifty clinically normal pre-menopausal non-pregnant women (100 breasts) were studied daily for one 'luteal positive' menstrual cycle. Their parity history varied from zero to five babies. Under controlled domestic conditions each wore a special electronic thermometric bra to automatically record breast 'core' temperature changes as a measure of mammary tissue blood flow. In the nulliparae there was a rise of breast vascularity throughout reproductive life. In the parous women, a year or so after each birth, breast vascularity was reset at a lower level than before the pregnancy; thereafter, as in nulliparae, there was progressive increase in mammary vascularity until the menopause.
- Published
- 2002
- Full Text
- View/download PDF
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