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1. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years

Author

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

Subjects
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.)

Published
2017

2. 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

Author

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

Subjects
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.

Published
2016
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3. Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials

Author

Early Breast Cancer Trialists' Collaborative Group (EBCTCG), Coleman, R, Powles, T, Paterson, A, Gnant, M, Anderson, S, Diel, I, Gralow, J, von Minckwitz, G, Moebus, V, Bergh, J, Pritchard, KI, Bliss, J, Cameron, D, Evans, V, Pan, H, Peto, R, Bradley, R, Gray, R, Bartsch, R, Dubsky, P, Fesl, C, Fohler, H, Greil, R, Jakesz, R, Lang, A, Luschin-Ebengreuth, G, Marth, C, Mlineritsch, B, Samonigg, H, Singer, CF, Steger, GG, Stoger, H, Olivotto, I, Ragaz, J, Christiansen, P, Ejlertsen, B, Ewertz, M, Jensen, M-B, Moller, S, Mouridsen, HT, Eiermann, W, Hilfrich, J, Jonat, W, Kaufmann, M, Kreienberg, R, Schumacher, M, Blohmer, JU, Costa, SD, Eidtmann, H, Gerber, B, Jackisch, C, Loibl, S, Dafni, U, Markopoulos, C, Blomqvist, C, Saarto, T, Ahn, J-H, Jung, KH, Perrone, F, 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, Perez, E, Ingle, JN, Suman, VJ, Hadji, P, A'Hern, R, Dowsett, M, Makris, A, Parton, M, Pennert, K, Powles, TJ, Smith, IE, Yarnold, JR, Clack, G, Van Poznak, C, Safra, T, Bell, R, Coleman, RE, Dodwell, D, Hinsley, S, Marshall, HC, Solomayer, E, Fehm, T, Lester, J, Winter, MC, Horsman, JM, Aft, R, Brufsky, AM, and Llombart, HA

Abstract

Background Bisphosphonates have profound effects on bone physiology, and could modify the process of metastasis. We undertook collaborative meta-analyses to clarify the risks and benefits of adjuvant bisphosphonate treatment in breast cancer. Methods We sought individual patient data from all unconfounded trials in early breast cancer that randomised between bisphosphonate and control. Primary outcomes were recurrence, distant recurrence, and breast cancer mortality. Primary subgroup investigations were site of first distant recurrence (bone or other), menopausal status (postmenopausal [combining natural and artificial] or not), and bisphosphonate class (aminobisphosphonate [eg, zoledronic acid, ibandronate, pamidronate] or other [ie, clodronate]). Intention-to-treat log-rank methods yielded bisphosphonate versus control first-event rate ratios (RRs). Findings We received data on 18 766 women (18 206 [97%] in trials of 2–5 years of bisphosphonate) with median follow-up 5·6 woman-years, 3453 first recurrences, and 2106 subsequent deaths. Overall, the reductions in recurrence (RR 0·94, 95% CI 0·87–1·01; 2p=0·08), distant recurrence (0·92, 0·85–0·99; 2p=0·03), and breast cancer mortality (0·91, 0·83–0·99; 2p=0·04) were of only borderline significance, but the reduction in bone recurrence was more definite (0·83, 0·73–0·94; 2p=0·004). Among premenopausal women, treatment had no apparent effect on any outcome, but among 11 767 postmenopausal women it produced highly significant reductions in recurrence (RR 0·86, 95% CI 0·78–0·94; 2p=0·002), distant recurrence (0·82, 0·74–0·92; 2p=0·0003), bone recurrence (0·72, 0·60–0·86; 2p=0·0002), and breast cancer mortality (0·82, 0·73–0·93; 2p=0·002). Even for bone recurrence, however, the heterogeneity of benefit was barely significant by menopausal status (2p=0·06 for trend with menopausal status) or age (2p=0·03), and it was non-significant by bisphosphonate class, treatment schedule, oestrogen receptor status, nodes, tumour grade, or concomitant chemotherapy. No differences were seen in non-breast cancer mortality. Bone fractures were reduced (RR 0·85, 95% CI 0·75–0·97; 2p=0·02). Interpretation Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival, but there is definite benefit only in women who were postmenopausal when treatment began. Funding Cancer Research UK, Medical Research Council.

Published
2015

4. 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

Author

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

Subjects
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

Published
2011
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5. Prevention of breast cancer

Author

Jones Al and Powles Tj

Subjects
CA15-3, Oncology, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Antineoplastic Agents, Breast Neoplasms, Disease, Breast cancer, Risk Factors, Internal medicine, Epidemiology of cancer, medicine, Humans, skin and connective tissue diseases, business.industry, Cancer, medicine.disease, Natural history, Tamoxifen, Female, business, Adjuvant, medicine.drug
Abstract

Breast cancer is the most common cancer in women in the United Kingdom and despite advances in treatment, metastatic disease remains incurable and many women die from the disease. There is extensive biologic and clinical evidence implicating estrogenic stimulation in the development and progression of breast cancer. The success of tamoxifen in adjuvant breast cancer trials in delaying the recurrence of disease and preventing second primary breast cancers and, in postmenopausal women, conferring a survival benefit, has led to increasing interest in the use of tamoxifen as a chemopreventive agent against breast cancer. It remains to be seen whether tamoxifen will act as a true preventive agent or whether it will merely delay the appearance of breast cancer, in which case the use of the drug may alter the natural history of the disease in women who have been exposed to tamoxifen. The optimal duration of drug intervention, the appropriate target population for chemoprevention, and the cost-benefit ratio of tamoxifen prevention are all issues that must be formally addressed in carefully controlled trials. Some data concerning duration and side effects are already available from epidemiologic studies and long-term clinical follow-up of patients exposed to tamoxifen.

Published
1991
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6. Editorial

Author

Powles Tj

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Text mining, business.industry, Adjuvant chemotherapy, Internal medicine, Medicine, business
Published
1998
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7. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials

Author

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

Subjects
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.

Published
2005

8. Effects of 5 years of treatment with lasofoxifene on incidence of breast cancer in older women.

Author

LaCroix, AZ, primary, Cummings, SR, additional, Delmas, P, additional, Eastell, R, additional, Ensrud, K, additional, Reid, DM, additional, Vukicevic, S, additional, Armstrong, RA, additional, Thompson, J, additional, Thompson, D, additional, Wolter, K, additional, Allred, C, additional, Goss, P, additional, Osborne, KC, additional, and Powles, TJ, additional

Published
2009
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9. The effects of norethisterone on endometrial abnormalities identified by transvaginal ultrasound screening of healthy post-menopausal women on tamoxifen or placebo

Author

Powles, TJ, primary, Bourne, T, additional, Athanasiou, S, additional, Chang, J, additional, Gruböck, K, additional, Ashley, S, additional, Oakes, L, additional, Tidy, A, additional, Davey, J, additional, Viggers, J, additional, Humphries, S, additional, and Collins, W, additional

Published
1998
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28. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation.

Author

Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, Norton L, Nickelsen T, Bjarnason NH, Morrow M, Lippman ME, Black D, Glusman JE, Costa A, Jordan VC, Cummings, S R, Eckert, S, Krueger, K A, Grady, D, and Powles, T J

Abstract

Context: Raloxifene hydrochloride is a selective estrogen receptor modulator that has antiestrogenic effects on breast and endometrial tissue and estrogenic effects on bone, lipid metabolism, and blood clotting.Objective: To determine whether women taking raloxifene have a lower risk of invasive breast cancer.Design and Setting: The Multiple Outcomes of Raloxifene Evaluation (MORE), a multicenter, randomized, double-blind trial, in which women taking raloxifene or placebo were followed up for a median of 40 months (SD, 3 years), from 1994 through 1998, at 180 clinical centers composed of community settings and medical practices in 25 countries, mainly in the United States and Europe.Participants: A total of 7705 postmenopausal women, younger than 81 (mean age, 66.5) years, with osteoporosis, defined by the presence of vertebral fractures or a femoral neck or spine T-score of at least 2.5 SDs below the mean for young healthy women. Almost all participants (96%) were white. Women who had a history of breast cancer or who were taking estrogen were excluded.Intervention: Raloxifene, 60 mg, 2 tablets daily; or raloxifene, 60 mg, 1 tablet daily and 1 placebo tablet; or 2 placebo tablets.Main Outcome Measures: New cases of breast cancer, confirmed by histopathology. Transvaginal ultrasonography was used to assess the endometrial effects of raloxifene in 1781 women. Deep vein thrombosis or pulmonary embolism were determined by chart review.Results: Thirteen cases of breast cancer were confirmed among the 5129 women assigned to raloxifene vs 27 among the 2576 women assigned to placebo (relative risk [RR], 0.24; 95% confidence interval [CI], 0.13-0.44; P<.001). To prevent 1 case of breast cancer, 126 women would need to be treated. Raloxifene decreased the risk of estrogen receptor-positive breast cancer by 90% (RR, 0.10; 95% CI, 0.04-0.24), but not estrogen receptor-negative invasive breast cancer (RR, 0.88; 95% CI, 0.26-3.0). Raloxifene increased the risk of venous thromboembolic disease (RR, 3.1; 95% CI, 1.5-6.2), but did not increase the risk of endometrial cancer (RR, 0.8; 95% CI, 0.2-2.7).Conclusion: Among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during 3 years of treatment with raloxifene. [ABSTRACT FROM AUTHOR]

Published
1999

32. Human breast tumour-induced osteolysis and prostaglandins

Author

Powles Tj, M. Dowsett, G. C. Easty, A. M. Neville, and D. M. Easty

Subjects
medicine.medical_specialty, Osteolysis, Indomethacin, Breast Neoplasms, Biochemistry, Bone resorption, Endocrinology, Internal medicine, medicine, Humans, Bone Resorption, Aspirin, Prostaglandins A, business.industry, Prostaglandins E, Prostaglandins F, medicine.disease, In vitro, Cancer research, Prostaglandins, lipids (amino acids, peptides, and proteins), Female, business, Human breast, medicine.drug
Abstract

Osteolysis effected in vitro by breast carcinomas can be inhibited by aspirin. Some prostaglandins stimulate in vitro bone resorption. Our results indicate that whilst osteolytically active PGE and PGF are released by the carcinomas in most cases, some other osteolytic principle is released as well.

Published
1976

33. Prostaglandin mediation of collagenase-induced bone resorption

Author

A. M. Neville, A. R. Eastman, G. C. Easty, M. Dowsett, Powles Tj, and D. M. Easty

Subjects
medicine.medical_specialty, Multidisciplinary, Lysis, Aspirin, Indomethacin, Prostaglandin synthesis, Prostaglandin, Bone resorption, Bone and Bones, chemistry.chemical_compound, Mice, Endocrinology, Microbial Collagenase, chemistry, Periodontal disease, Internal medicine, Culture Techniques, Bone cell, medicine, Collagenase, Prostaglandins, Animals, Bone Resorption, medicine.drug
Abstract

PATHOLOGICAL bone breakdown may be stimulated by some tissues proximal to bone and the release of collagenase by them may be one cause of this lysis. Inflamed gingivae, for example, have been shown to lyse collagen gels1,2 and are associated with the loss of bone in periodontal disease. The ability of human mammary carcinomas to break down bone in vitro3,4 has been shown to be caused, in part, by prostaglandin release by the tumours5 and, in part, by their release of an osteolytically active, non-dialysable material (unpublished results). The possibility that the latter might be collagenolytic in nature was suggested by reports that some neoplasms release collagenolytic activity in vitro6–9. This prompted our present study of the mechanism of bone breakdown by exogenous collagenase. The investigation has shown that prostaglandin synthesis by bone cells is probably a necessary mediatory step in collagenase-induced bone resorption.

Published
1976

34. A Control Randomised Trial Comparing Vindesine and Adriamycin with Vincristine and Adriamycin in the Treatment of Advanced Breast Carcinoma

Author

J. C. Gazet, R. C. Coombes, I. E. Smith, H. T. Ford, J. A. McKinna, Clive Harmer, and Powles Tj

Subjects
Oncology, Vincristine, medicine.medical_specialty, business.industry, Advanced breast, Neurotoxicity, medicine.disease, Internal medicine, Toxicity, medicine, Carcinoma, Vindesine, business, medicine.drug
Abstract

SummaryIn a control randomised trial 17 out of 29 assessable patients with advanced breast carcinoma responded to a combination of vincristine and adriamycin (59 %) compared with 16 out of 26 patients treated with vindesine and adriamycin (62 %). Six patients (21 %) treated with vincristine experienced neurotoxicity severe enough to reduce dosage or stop treatment compared with only 2 (8 %) treated with vindesine. No difference was seen in marrow toxicity between the 2 schedules.

Published
1981
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37. EFFECTS OF RADIOTHERAPY AND SURGERY IN EARLY BREAST-CANCER - AN OVERVIEW OF THE RANDOMIZED TRIALS

Author

Abe, O., Abe, R., Asaishi, K., Enomoto, K., Hattori, T., Iino, Y., Kikuchi, K., Koyama, H., Sawa, K., Uchino, J., Yoshida, M., Vandevelde, Ao, Vermorken, Jb, Foroglou, P., Giokas, G., Lissaios, B., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Forbes, Jf, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schumacher, M., Gelman, Rs, Henderson, Ic, Shapiro, Cl, Hancock, Ak, Jackson, S., Ragaz, J., Delozier, T., Macelesech, J., Haybittle, Jl, Cirrincione, C., Korzun, A., Weiss, Rb, Wood, Wc, Baum, M., Houghton, J., Riley, D., Dent, Dm, Gudgeon, Ca, Hacking, A., Horgan, K., Hughes, L., Stewart, Hj, Gordon, Nh, Davis, Hl, Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Albano, J., Deoliveira, Cf, Gervasio, H., Gordilho, J., Carstensen, B., Palshof, T., Johansen, H., Korzeniowski, S., Skolyszewski, J., Andersen, Kw, Axelsson, Ck, Blicherttoft, M., Mouridsen, Ht, Overgaard, M., Rose, C., Corcoran, N., Trampisch, Hj, Abeloff, Md, Carbone, Pc, Glick, J., Gray, R., Tormey, Dc, Bartelink, H., Fentiman, Is, Paridaens, R., Vandriel, Ojr, Sylvester, Rj, Vandevelde, Cjh, Vanderschueren, E., Vandongen, Ja, Welvaart, K., Scanlon, Ef, Schurman, S., Deschryver, A., Yosef, Hma, Mcardle, Cs, Smith, Dc, Lara, Pc, Boccardo, F., Izuo, M., Morishita, Y., Bentley, A., Doran, Z., Hayward, Jl, Rubens, Rd, Kaufmann, M., Jonat, W., Scheurlen, H., Vonfournier, D., Klefstrom, P., Cuzick, J., Margreiter, R., Cavalli, F., Collins, J., Gelber, Rd, Goldhirsch, A., ISLEY, MR, Lindtner, J., Price, Kn, Rudenstam, Cm, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Marty, M., Brufman, G., Hayat, H., Borovik, R., Robinson, E., Pannuti, F., Takashima, S., Yasutomi, T., Sonoo, H., Yamashita, J., Ogawa, M., Nomura, Y., Bonte, J., Tengrup, I., Tennvallnittby, L., Martin, P., Romain, S., Ahmann, D., Schaid, Dj, Buzdar, Au, Smith, T., Hakes, T., Norton, L., Wittes, R., Delahuerta, R., Sainz, Mg, Bonadonna, G., Delvecchio, M., Valagussa, P., Veronesi, U., Dubois, Jb, Bianco, Ar, Lippman, Me, Pierce, Lj, Simon, R., Steinberg, Sm, Brown, A., Fisher, B., Redmond, C., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Bengtsson, No, Larsson, Lg, Lythgoe, Jp, Kissin, M., Hannisdal, E., Varhaug, Je, Blamey, Rw, Mitchell, Ak, Robertson, Jfr, Nakamura, Y., Mathe, G., Misset, Jl, Clarke, Ea, Mclaughlin, Jr, Clark, Rm, Levine, M., Morimoto, K., Gundersen, S., Hauerjensen, M., Host, H., Crossley, E., Durrant, K., Harris, A., Beighton, A., Chadbon, D., Clarke, M., Collins, R., Davies, C., Evans, V., Godwin, J., Greaves, E., Harwood, C., James, S., Mead, G., Muldahl, A., Peto, R., Tooth, A., Wheatley, K., Rambert, P., Asselain, B., Salmon, Rj, Vilcoq, Jr, Arriagada, R., Hill, C., Laplanche, A., Le, Mg, Spielmann, M., Cocconi, G., Diblasio, B., Catalano, R., Creech, Rh, Brockschmidt, J., COOPER, MR, Andrysek, O., Barkmanova, J., Treurnietdonker, Ad, Vanputten, Wlj, Easton, D., Powles, Tj, Gazet, Jc, Semiglazov, V., Deshpande, N., Dimartino, L., Douglas, P., Lindtner, A., Notter, G., Nissenmeyer, R., Forrest, Apm, Jack, W., Mcdonald, C., Moller, Tr, Ryden, S., Carstensen, J., Hatschek, T., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Osborne, Ck, Rutquist, Le, Wallgren, A., Holm, Le, Castiglione, M., Fluckiger, H., Thurlimann, B., Hermann Brenner, Hercbergs, A., Yoshimoto, M., Deboer, G., Paterson, Ahg, Pritchard, Ki, Meakin, Jw, Panzarella, T., Naja, A., Bahi, J., Reid, M., Spittler, M., Senanayake, F., Holmberg, L., Sevelda, P., Zielinsky, Cc, Jakesz, R., Buchanan, Rb, Cross, M., Dunn, Ja, Gillespie, Wm, Kelly, K., Morrison, Jm, Litton, A., Chlebowski, Rt, Bezwoda, Wr, and Caffier, H.

38. Ovarian ablation in early breast cancer: Overview of the randomised trials

Author

Clarke, M., Collins, R., Davies, C., Godwin, J., Gray, R., Peto, R., Abe, O., Abe, R., Enomoto, K., Kikuchi, K., Koyama, H., Nomura, Y., Sakai, K., Sugimachi, K., Tominaga, T., Uchino, J., Yoshida, M., Vandevelde, Ao, Vandongen, Ja, Vermorken, Jb, Arvelakis, A., Giokas, G., Lissaios, B., Harvey, Vj, Holdaway, Tm, Kay, Rg, Mason, Bh, Coates, A., Forbes, Jf, Focan, C., Lobelle, Jp, Peek, U., Oates, Gd, Powell, J., Bastert, G., Rauschecker, H., Sauer, R., Sauerbrei, W., Schauer, A., Schumacher, M., Durand, M., Mauriac, L., Bartholomeus, S., Piccart, Mj, Gelman, Rs, Henderson, Ic, Shapiro, Cl, Hancock, Ak, Masood, Mb, Parker, D., Price, Jj, Jackson, S., Ragaz, J., Delozier, T., Macelesech, J., Haybittle, Jl, Cirrincione, C., Korzun, A., Weiss, Rb, Wood, Wc, Baum, M., Houghton, J., Riley, D., Dent, Dm, Gudgeon, Ca, Hacking, A., Horgan, K., Hughes, L., Stewart, Hj, Gordon, Nh, Davis, Hl, Lehingue, Y., Owen, Jr, Meier, P., Howell, A., Ribeiro, Gc, Swindell, R., Albano, J., Deoliveira, Cf, Gervasio, H., Gordilho, J., Carstensen, B., Palshof, T., Johansen, H., Korzeniowski, S., Skolyszewski, J., Andersen, Kw, Axelsson, Ck, Blicherttoft, M., Mouridsen, Ht, Overgaard, M., Rose, C., Corcoran, N., Trampisch, Hj, Abeloff, Md, Carbone, Pc, Glick, J., Tormey, Dc, Rossbach, J., Scanlon, Ef, Schurman, S., Deschryver, A., Yosef, Hma, Mcardle, Cs, Smith, Dc, Lara, Pc, Boccardo, F., Erazo, A., Medina, Jy, Izuo, M., Morishita, Y., Bentley, A., Doran, Z., Fentiman, Is, Hayward, Jl, Rubens, Rd, Kaufmann, M., Jonat, W., Scheurlen, H., Vonfournier, D., Fountzilas, G., Klefstrom, P., Blomqvist, C., Cuzick, J., Margreiter, R., Castiglione, M., Cavalli, F., Collins, J., Forbes, J., Gelber, Rd, Goldhirsch, A., Lindtner, J., Price, Kn, Rudenstam, Cm, Senn, Hj, Bliss, Jm, Chilvers, Ced, Coombes, Rc, Marty, M., Borovik, R., Brufman, G., Hayat, H., Robinson, E., Wigler, N., Pannuti, F., Takashima, S., Tasutomi, T., Sonoo, H., Yamashita, J., Ogawa, M., Hupperets, Psgj, Bonte, J., Tengrup, I., Tennvallnittby, L., Martin, P., Romain, S., Ahmann, D., Schaid, Dj, Buzdar, Au, Smith, T., Hakes, T., Norton, L., Wittes, R., Delahuerta, R., Sainz, Mg, Bonadonna, G., Delvecchio, M., Valagussa, P., Veronesi, U., Dubois, Jb, Bianco, Ar, Lippman, Me, Pierce, Lj, Simon, R., Steinberg, Sm, Brown, A., Fisher, B., Redmond, C., Wolmark, N., Jackson, Im, Palmer, Mk, Ingle, Jn, Suman, Vj, Bengtsson, No, Larsson, Lg, Lythgoe, Jp, Kissin, M., Hannisdal, E., Varhaug, Je, Nissenmeyer, R., Blamey, Rw, Mitchell, Ak, Robertson, Jfr, Nakamura, Y., Mathe, G., Misset, Jl, Abuzahra, Ht, Clarke, Ea, Mclaughlin, Jr, Clark, Rm, Levine, M., Myles, Jd, Pater, Jl, Pritchard, Ki, Morimoto, K., Sawa, K., Takatsuka, Y., Gundersen, S., Hauerjensen, M., Host, A., Crossley, E., Durrant, K., Harris, A., Beighton, A., Evans, V., Greaves, E., Harwood, C., James, S., Lau, E., Mead, G., Muldal, A., Naughton, A., Tooth, A., Wheatley, K., Rambert, P., Asselain, B., Salmon, Rj, Vilcoq, Jr, Rodrigo Arriagada, Hill, C., Laplanche, A., Le, Mg, Speilmann, M., Cocconi, G., Diblasio, B., Catalano, R., Creech, Rh, Brockschmidt, J., Cooper, MR, Andrysek, O., Barkmanova, J., Falkson, Cj, Abraham, M., Klijn, Jgm, Treurnietdonker, Ad, Vanputten, Wlj, Easton, D., Powles, Tj, Gazet, Jc, Semiglazov, V., Deshpande, N., Dimartino, L., Douglas, P., Host, H., Bryant, Ajs, Ewing, Gh, Krushenkosloski, Jl, Forrest, Apm, Jack, W., Mcdonald, C., Moller, Tr, Ryden, S., Carstensen, J., Hatschek, T., Soderberg, M., Carpenter, Jt, Albain, K., Crowley, J., Green, S., Martino, S., Osborne, Ck, Ravdin, Pm, Rutqvist, Le, Wallgren, A., Holm, Le, Yoshimoto, M., Deboer, G., Paterson, Ahg, Meakin, Jw, Panzarella, T., Naja, A., Bahi, J., Reid, M., Spittle, M., Senanayake, F., Bergh, J., Holmberg, L., Sevelda, P., Zielinsky, Cc, Jakesz, R., Gnant, M., Buchanan, Rb, Cross, M., Dunn, Ja, Gillespie, Wm, Kelly, K., Morrison, Jm, Litton, A., Chlebowski, Rt, Bezwoda, Wr, Caffier, H., Clarke, M, Collins, R, Davies, C, Godwin, J, Gray, R, Peto, R, Abe, O, Abe, R, Enomoto, K, Kikuchi, K, Koyama, H, Nomura, Y, Sakai, K, Sugimachi, K, Tominaga, T, Uchino, J, Yoshida, M, vandeVelde, A, vanDongen, J, Vermorken, J, Arvelakis, A, Giokas, G, Lissaios, B, Harvey, V, and Holdaway, T

Subjects
Oncology, medicine.medical_specialty, Breast cancer, business.industry, Internal medicine, medicine, Ovarian Ablation, General Medicine, business, medicine.disease, Early breast cancer
Abstract

Background Among women with early breast cancer, the effects of ovarian ablation on recurrence and death have been assessed by several randomised trials that now have long follow-up. In this report, the Early Breast Cancer Trialists' Collaborative Group present their third 5-yearly systematic overview (meta-analysis), now with 15 years' follow-up. Methods In 1995, information was sought on each patient in any randomised trial of ovarian ablation or suppression versus control that began before 1990. Data were obtained for 12 of the 13 studies that assessed ovarian ablation by irradiation or surgery, all of which began before 1980, but not for the four studies that assessed ovarian suppression by drugs, all of which began after 1985. Menopausal status was not consistently defined across trials; therefore, the main analyses are limited to women aged under 50 (rather than “premenopausal”) when randomised. Oestrogen receptors were measured only in the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone. Findings Among 2102 women aged under 50 when randomised, most of whom would have been premenopausal at diagnosis, 1130 deaths and an additional 153 recurrences were reported. 15-year survival was highly significantly improved among those allocated ovarian ablation (52·4 vs46·1%, 6·3 [SD 2·3] fewer deaths per 100 women, logrank 2p=0·001), as was recurrence-free survival (45·0 vs 39·0%, 2p=0·0007). The numbers of events were too small for any subgroup analyses to be reliable. The benefit was, however, significant both for those with (“node positive”) and for those without (“node negative”) axillary spread when diagnosed. In the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone, the benefit appeared smaller (even for women with oestrogen receptors detected on the primary tumour) than in the trials of ablation in the absence of chemotherapy (where the observed survival improvements were about six per 100 node-negative women and 12 per 100 node-positive women). Among 1354 women aged 50 or over when randomised, most of whom would have been perimenopausal or postmenopausal, there was only a nonsignificant improvement in survival and recurrence-free survival. improves long-term survival, at least in the absence of chemotherapy. Further randomised evidence is needed on the additional effects of ovarian ablation in the presence of other adjuvant treatments, and to assess the relevance of hormone-receptor measurements. Interpretation In women aged under 50 with early breast cancer, ablation of functioning ovaries significantly.

39. Tumor-Induced Osteolysis

Author

D.M Easty, Powles Tj, G.C. Easty, and A.M Neville

Subjects
Aspirin, Osteolysis, Text mining, business.industry, medicine, Cancer research, General Medicine, medicine.disease, business, Bone resorption, medicine.drug
Published
1974
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41. Effects of tamoxifen on uterus and ovaries of postmenopausal women in a randomised breast cancer prevention trial.

Author

Kedar RP, Bourne TH, Powles TJ, Collins WP, Ashley SE, Cosgrove DO, Campbell S, Kedar, R P, Bourne, T H, Powles, T J, Collins, W P, Ashley, S E, Cosgrove, D O, and Campbell, S

Abstract

Randomised, double-blind controlled trials have been started to determine whether tamoxifen can prevent or delay development of breast cancer in healthy women with a family history of the disease. We recruited a randomised cohort of 111 postmenopausal women (aged 46-71 years) from the Pilot Breast Cancer Prevention Trial at the Royal Marsden Hospital to study the effect of tamoxifen on the uterus and ovaries. The main outcome measures were obtained by transvaginal ultrasonography with colour doppler imaging and microscopic examination of endometrial biopsies removed at the time of the scan. There was no significant difference between tamoxifen (20 mg/day) and placebo groups in the age of the women, or the time of the scan (and sampling) after randomisation. Women taking tamoxifen had a significantly larger uterus and a lower impedance to blood flow in the uterine arteries. 39% of women taking tamoxifen had histological evidence of an abnormal endometrium compared with 10% in the control group. 10 patients in the tamoxifen group (16%) had atypical hyperplasia and another 5 (8%) had a polyp. Women with a histological abnormality had a significantly thicker endometrium and a decreased impedance to blood flow in the uterine arteries. There was no correlation between the presence of uterine abnormalities and the age of the women, or the concentrations of tamoxifen or desmethyl tamoxifen in the peripheral blood. These findings confirm that tamoxifen can cause potentially malignant changes in the endometrium of postmenopausal women. Transvaginal ultrasonography can be used to identify those women who should have endometrial samples removed for microscopic analysis. [ABSTRACT FROM AUTHOR]

Published
1994
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44. Impact of a Panel of 88 Single Nucleotide Polymorphisms on the Risk of Breast Cancer in High-Risk Women: Results From Two Randomized Tamoxifen Prevention Trials.

Author

Cuzick J, Brentnall AR, Segal C, Byers H, Reuter C, Detre S, Lopez-Knowles E, Sestak I, Howell A, Powles TJ, Newman WG, and Dowsett M

Subjects
Breast Neoplasms diagnosis, Breast Neoplasms metabolism, Case-Control Studies, Estrogen Antagonists administration & dosage, Female, Genetic Predisposition to Disease, Humans, Middle Aged, Polymorphism, Single Nucleotide, Receptors, Estrogen metabolism, Anticarcinogenic Agents administration & dosage, Breast Neoplasms genetics, Breast Neoplasms prevention & control, Tamoxifen administration & dosage
Abstract

Purpose At least 94 common single nucleotide polymorphisms (SNPs) are associated with breast cancer. The extent to which an SNP panel can refine risk in women who receive preventive therapy has not been directly assessed previously. Materials and Methods A risk score on the basis of 88 SNPs (SNP88) was investigated in a nested case-control study of women enrolled in the International Breast Intervention Study (IBIS-I) or the Royal Marsden study. A total of 359 women who developed cancer were matched to 636 controls by age, trial, follow-up time, and treatment arm. Genotyping was done using the OncoArray. Conditional logistic regression and matched concordance indices (mC) were used to measure the performance of SNP88 alone and with other breast cancer risk factors assessed using the Tyrer-Cuzick (TC) model. Results SNP88 was predictive of breast cancer risk overall (interquartile range odds ratio [IQ-OR], 1.37; 95% CI, 1.14 to 1.66; mC, 0.55), but mainly for estrogen receptor-positive disease (IQ-OR, 1.44; 95% CI, 1.16 to 1.79; P for heterogeneity = .10) versus estrogen receptor-negative disease. However, the observed risk of SNP88 was only 46% (95% CI, 19% to 74%) of expected. No significant interaction was observed with treatment arm (placebo IQ-OR, 1.46; 95% CI, 1.13 to 1.87; tamoxifen IQ-OR, 1.25; 95% CI, 0.96 to 1.64; P for heterogeneity = .5). The predictive power was similar to the TC model (IQ-OR, 1.45; 95% CI, 1.21 to 1.73; mC, 0.55), but SNP88 was independent of TC (Spearman rank-order correlation, 0.012; P = .7), and when combined multiplicatively, a substantial improvement was seen (IQ-OR, 1.64; 95% CI, 1.36 to 1.97; mC, 0.60). Conclusion A polygenic risk score may be used to refine risk from the TC or similar models in women who are at an elevated risk of breast cancer and considering preventive therapy. Recalibration may be necessary for accurate risk assessment.

Published
2017
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45. Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial.

Author

Detre SI, Ashley S, Mohammed K, Smith IE, Powles TJ, and Dowsett M

Subjects
Adult, Aged, Double-Blind Method, ErbB Receptors analysis, ErbB Receptors biosynthesis, Female, Follow-Up Studies, Humans, Immunohistochemistry, Ki-67 Antigen analysis, Ki-67 Antigen biosynthesis, Middle Aged, Phenotype, Receptor, ErbB-2 analysis, Receptor, ErbB-2 biosynthesis, Receptors, Estrogen analysis, Receptors, Estrogen biosynthesis, Receptors, Progesterone analysis, Receptors, Progesterone biosynthesis, Biomarkers, Tumor analysis, Breast Neoplasms prevention & control, Selective Estrogen Receptor Modulators therapeutic use, Tamoxifen therapeutic use
Abstract

The randomized, double-blinded Royal Marsden Tamoxifen Breast Cancer Prevention Trial in healthy high-risk women started in 1986 and is still blinded. Eligible participants ( n = 2,471) were randomly assigned to tamoxifen (20 mg/d) or placebo for 8 years. Analysis in 2006 showed a 30% risk reduction of estrogen receptor (ER)-positive invasive breast cancer mostly in the posttreatment period. Biomarker analysis in this population may identify any subgroup-specific preventive effects tamoxifen. After a median follow-up of 18.4 years, 242 patients had developed invasive cancer, 134 on placebo and 108 on tamoxifen. From these, 180 tissue blocks were available and ER, progesterone receptor (PgR), Ki67, HER2, and EGFR were immunohistochemically analyzed. A 32% reduction in ER + and PgR + invasive cancers resulted after 8 years of treatment. Quantitative levels of ER and PgR were lower in the tamoxifen-treated group, significantly so for ER ( P = 0.001). These lower ER levels were restricted to the posttreatment period ( P = 0.018). Among the ER + group, there was a similar proportional decrease in PgR + and PgR - tumors by tamoxifen. The median levels of Ki67 were similar in both arms. The numbers of HER2-positive and EGFR-positive cancers were higher in the tamoxifen arm but not significantly so. In conclusion, the preventive effects of tamoxifen result in reduced ER-positive but not ER-negative tumors and reduced ER expression in the ER-positive cases largely confined to the posttreatment period. Overall reductions in PgR expression are explained by lower frequency of ER-positive cases. Impact on Ki67, HER2, and EGFR was modest. Cancer Prev Res; 10(3); 171-6. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Published
2017
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46. Relationship of ZNF423 and CTSO with breast cancer risk in two randomised tamoxifen prevention trials.

Author

Brentnall AR, Cuzick J, Byers H, Segal C, Reuter C, Detre S, Sestak I, Howell A, Powles TJ, Newman WG, and Dowsett M

Subjects
Breast Neoplasms genetics, Case-Control Studies, Female, Humans, Logistic Models, Middle Aged, Odds Ratio, Proteins, Randomized Controlled Trials as Topic, Antineoplastic Agents, Hormonal therapeutic use, Breast Neoplasms prevention & control, Cathepsins genetics, DNA-Binding Proteins genetics, Polymorphism, Single Nucleotide, Tamoxifen therapeutic use
Abstract

A case-control study from two randomised breast cancer prevention trials of tamoxifen and raloxifene (P-1 and P-2) identified single-nucleotide polymorphisms (SNPs) in or near genes ZNF423 and CTSO as factors which predict which women will derive most anti-cancer benefit from selective oestrogen receptor modulator (SERM) therapy. In this article, we further examine this question using blood samples from two randomised tamoxifen prevention trials: the International Breast Cancer Intervention Study I (IBIS-I) and the Royal Marsden trial (Marsden). A nested case-control study was designed with 2:1 matching in IBIS-I and 1:1 matching in Marsden. The OncoArray was used for genotyping and included two SNPs previously identified (rs8060157 in ZNF423 and rs10030044 near CTSO), and 102 further SNPs within the same regions. Overall, there were 369 cases and 662 controls, with 148 cases and 268 controls from the tamoxifen arms. Odds ratios were estimated by conditional logistic regression, with Wald 95 % confidence intervals. In the tamoxifen arms, the per-allele odds ratio for rs8060157 was 0.99 (95 %CI 0.73-1.34) and 1.00 (95 %CI 0.76-1.33) for rs10030044. In the placebo arm, the odds ratio was 1.10 (95 %CI 0.87-1.40) for rs8060157 and 1.01 (95 %CI 0.79-1.29) for rs10030044. There was no evidence to suggest that other SNPs in the surrounding regions of these SNPs might predict response to tamoxifen. Results from these two prevention trials do not support the earlier findings. rs8060157 in ZNF423 and rs10030044 near CTSO do not appear to predict response to tamoxifen.

Published
2016
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47. Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel.

Author

Hadji P, Coleman RE, Wilson C, Powles TJ, Clézardin P, Aapro M, Costa L, Body JJ, Markopoulos C, Santini D, Diel I, Di Leo A, Cameron D, Dodwell D, Smith I, Gnant M, Gray R, Harbeck N, Thurlimann B, Untch M, Cortes J, Martin M, Albert US, Conte PF, Ejlertsen B, Bergh J, Kaufmann M, and Holen I

Subjects
Antineoplastic Agents therapeutic use, Bone Neoplasms secondary, Chemotherapy, Adjuvant, Clodronic Acid adverse effects, Clodronic Acid therapeutic use, Consensus, Diphosphonates adverse effects, Europe, Female, Humans, Imidazoles adverse effects, Imidazoles therapeutic use, Neoplasm Recurrence, Local drug therapy, Osteoporosis chemically induced, Osteoporosis drug therapy, Surveys and Questionnaires, Zoledronic Acid, Antineoplastic Agents adverse effects, Bone Density Conservation Agents therapeutic use, Bone Neoplasms prevention & control, Breast Neoplasms drug therapy, Diphosphonates therapeutic use, Neoplasm Recurrence, Local prevention & control, Osteoporosis prevention & control
Abstract

Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus. The panel recommended that bisphosphonates should be considered as part of routine clinical practice for the prevention of CTIBL in all patients with a T score of <-2.0 or ≥2 clinical risk factors for fracture. Compelling evidence from a meta-analysis of trial data of >18,000 patients supports clinically significant benefits of bisphosphonates on the development of bone metastases and breast cancer mortality in post-menopausal women or those receiving ovarian suppression therapy. Therefore, the panel recommends that bisphosphonates (either intravenous zoledronic acid or oral clodronate) are considered as part of the adjuvant breast cancer treatment in this population and the potential benefits and risks discussed with relevant patients., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2016
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50. Breast cancer incidence in postmenopausal women with osteoporosis or low bone mass using arzoxifene.

Author

Powles TJ, Diem SJ, Fabian CJ, Neven P, Wickerham DL, Cox DA, Muram D, Agnusdei D, Dowsett SA, Amewou-Atisso M, and Cummings SR

Subjects
Aged, Breast Neoplasms epidemiology, Carcinoma, Ductal, Breast epidemiology, Double-Blind Method, Female, Fractures, Bone epidemiology, Fractures, Bone etiology, Fractures, Bone prevention & control, Humans, Middle Aged, Osteoporosis, Postmenopausal complications, Risk Factors, Antineoplastic Agents therapeutic use, Breast Neoplasms prevention & control, Carcinoma, Ductal, Breast prevention & control, Osteoporosis, Postmenopausal drug therapy, Piperidines therapeutic use, Postmenopause, Thiophenes therapeutic use
Abstract

The Generations trial, a multicenter, placebo-controlled, double-blind trial, compared arzoxifene 20 mg/day and placebo in 9,354 postmenopausal women with osteoporosis (N=5,252) or low bone mass (N=4,102). Primary outcomes were vertebral fracture in the osteoporotic population and invasive breast cancer in all study participants. Here, we report the detailed breast cancer findings from the trial. Breast cancers were detected by annual mammograms and clinical examination. After 48 months follow-up, breast cancer incidence was compared between treatment groups by estrogen receptor (ER) and progesterone receptor (PR) status and baseline risk factors. Baseline breast cancer risk factors, including age, estimated Gail risk, and bone mineral density, were well balanced between treatment groups. A total of 75 breast cancers occurred 53 in the placebo group and 22 in the arzoxifene group (HR 0.41, 95% CI 0.25-0.68, P<0.001). There were 62 invasive breast cancers, 39 identified as invasive ER-positive (placebo 30, arzoxifene 9; HR 0.30, 95% CI 0.14-0.63, P=0.001) and 30 identified as invasive PR-positive (placebo 23, arzoxifene 7; HR 0.30, 95% CI 0.13-0.71, P=0.003). Breast cancer risk reduction with arzoxifene was similar between Gail risk groups (P interaction=0.31) and between low bone mass and osteoporosis groups (P interaction=0.35). Although generally well tolerated, there was a significant increase in venous thromboembolism, vasomotor symptoms, muscle cramps, and some gynecological events with arzoxifene. These findings demonstrate that in this study arzoxifene reduced the risk of ER-positive breast cancer in this population of postmenopausal women with low bone mass or osteoporosis, an effect similar to that seen with other SERMs.

Published
2012
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