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1. Molecular risk assessment of BIG 1-98 participants by expression profiling using RNA from archival tissue

Author

Giobbie-Hurder Anita, Thürlimann Beat, Oberli Andrea, Baltzer Anna, Wirapati Pratyaksha, Delorenzi Mauro, Popovici Vlad, Antonov Janine, Viale Giuseppe, Altermatt Hans, Aebi Stefan, and Jaggi Rolf

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The purpose of the work reported here is to test reliable molecular profiles using routinely processed formalin-fixed paraffin-embedded (FFPE) tissues from participants of the clinical trial BIG 1-98 with a median follow-up of 60 months. Methods RNA from fresh frozen (FF) and FFPE tumor samples of 82 patients were used for quality control, and independent FFPE tissues of 342 postmenopausal participants of BIG 1-98 with ER-positive cancer were analyzed by measuring prospectively selected genes and computing scores representing the functions of the estrogen receptor (eight genes, ER_8), the progesterone receptor (five genes, PGR_5), Her2 (two genes, HER2_2), and proliferation (ten genes, PRO_10) by quantitative reverse transcription PCR (qRT-PCR) on TaqMan Low Density Arrays. Molecular scores were computed for each category and ER_8, PGR_5, HER2_2, and PRO_10 scores were combined into a RISK_25 score. Results Pearson correlation coefficients between FF- and FFPE-derived scores were at least 0.94 and high concordance was observed between molecular scores and immunohistochemical data. The HER2_2, PGR_5, PRO_10 and RISK_25 scores were significant predictors of disease free-survival (DFS) in univariate Cox proportional hazard regression. PRO_10 and RISK_25 scores predicted DFS in patients with histological grade II breast cancer and in lymph node positive disease. The PRO_10 and PGR_5 scores were independent predictors of DFS in multivariate Cox regression models incorporating clinical risk indicators; PRO_10 outperformed Ki-67 labeling index in multivariate Cox proportional hazard analyses. Conclusions Scores representing the endocrine responsiveness and proliferation status of breast cancers were developed from gene expression analyses based on RNA derived from FFPE tissues. The validation of the molecular scores with tumor samples of participants of the BIG 1-98 trial demonstrates that such scores can serve as independent prognostic factors to estimate disease free survival (DFS) in postmenopausal patients with estrogen receptor positive breast cancer. Trial Registration Current Controlled Trials: NCT00004205

Published
2010
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2. Multiplexed high-throughput immune cell imaging in patients with high-risk triple negative early breast cancer: Analysis from the International Breast Cancer Study Group (IBCSG) Trial 22-00

Author

Rusakiewicz, S., Tyekucheva, S., Tissot-Renaud, S., Chaba, K., Imbimbo, M., Benedetti, F., Kammler, R., Hornfeld, J., Munzone, E., Gianni, L., Thurlimann, B., Láng, I., Pruneri, G., Gray, K.P., Regan, M.R., Loi, S., Colleoni, M., Viale, G., Kandalaft, L., Coukos, G., and Curigliano, Giuseppe

Published
2024
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4. Adjuvant bisphosphonates in early breast cancer: consensus guidance for clinical practice from a European Panel

Author

Hadji, P., Coleman, R.E., Wilson, C., Powles, T.J., Clézardin, P., Aapro, M., Costa, L., Body, J.-J., 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, U.-S., Conte, P.-F., Ejlertsen, B., Bergh, J., Kaufmann, M., and Holen, I.

Published
2016
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5. Genomic characterisation of hormone receptor-positive breast cancer arising in very young women

Author

Luen, SJ, Viale, G, Nik-Zainal, S, Savas, P, Kammler, R, Dell'Orto, P, Biasi, O, Degasperi, A, Brown, LC, Lang, I, MacGrogan, G, Tondini, C, Bellet, M, Villa, F, Bernardo, A, Ciruelos, E, Karlsson, P, Neven, P, Climent, M, Mueller, B, Jochum, W, Bonnefoi, H, Martino, S, Davidson, NE, Geyer, C, Chia, SK, Ingle, JN, Coleman, R, Solbach, C, Thurlimann, B, Colleoni, M, Coates, AS, Goldhirsch, A, Fleming, GF, Francis, PA, Speed, TP, Regan, MM, Loi, S, Luen, SJ, Viale, G, Nik-Zainal, S, Savas, P, Kammler, R, Dell'Orto, P, Biasi, O, Degasperi, A, Brown, LC, Lang, I, MacGrogan, G, Tondini, C, Bellet, M, Villa, F, Bernardo, A, Ciruelos, E, Karlsson, P, Neven, P, Climent, M, Mueller, B, Jochum, W, Bonnefoi, H, Martino, S, Davidson, NE, Geyer, C, Chia, SK, Ingle, JN, Coleman, R, Solbach, C, Thurlimann, B, Colleoni, M, Coates, AS, Goldhirsch, A, Fleming, GF, Francis, PA, Speed, TP, Regan, MM, and Loi, S

Abstract

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% v

Published
2023

6. Historical early treatment effects of adjuvant endocrine therapy for breast cancer in high-risk subgroups: Reanalysis of BIG 1-98, SOFT and TEXT.

Author

Regan, Meredith M., primary, Niman, Samuel M., additional, Fleming, Gini F., additional, Walley, Barbara, additional, Viale, Giuseppe, additional, Thurlimann, Beat J. K., additional, Loi, Sherene, additional, Colleoni, Marco, additional, Pagani, Olivia, additional, and Francis, Prudence A., additional

Published
2022
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7. Historical early treatment effects of adjuvant endocrine therapy for breast cancer in high-risk subgroups: Reanalysis of BIG 1-98, SOFT and TEXT

Author

Meredith M. Regan, Samuel M. Niman, Gini F. Fleming, Barbara Walley, Giuseppe Viale, Beat J. K. Thurlimann, Sherene Loi, Marco Colleoni, Olivia Pagani, and Prudence A. Francis

Subjects
Cancer Research, Oncology
Abstract

508 Background: Clinical trials testing adjuvant endocrine therapy (ET) have not historically limited enrollment to patients with clinically high-risk breast cancer (BC), nor estimated treatment (trt) effects prior to 5 yrs. In light of recent trial results for adjuvant CDK4/6 inhibitors, we estimated early relative and absolute trt effects of aromatase inhibitor (AI) vs tamoxifen (T), with ovarian suppression (OFS) if premenopausal, in high risk subgroups. Methods: From pts enrolled in adjuvant phase 3 randomized clinical trials BIG 1-98 (postmenopausal, 5yr AI v T), TEXT (5yr AI+OFS v T+OFS) and SOFT (5yr AI+OFS v T+OFS v T), we identified subgroups with HR+/HER2- BC and high risk features (≥4 pLN; or 1-3 pLN with grade 3, pT≥5 cm and/or Ki-67≥20% [retrospectively centrally assessed]). TEXT randomized at start of adjuvant trt; BIG 1-98 and SOFT after chemotherapy. Disease-free survival (DFS) was defined from randomization to invasive recurrence at local, regional, distant or contralateral breast, second non-breast malignancy or death. We estimated trt effects as differences in 2, 3 and 5yr DFS Kaplan-Meier estimates (KM diffs at t yrs) and hazard ratios over time intervals of 0-2, 0-3 and 0-5 yrs (HRs over 0 to t yrs) to approximate the maturity of trial results with increasing follow-up. Results: The high-risk HR+/HER2- subgroups were 695/4922, 707/2660 and 526/3047 pts in BIG 1-98, TEXT and SOFT with 202, 122, 142 DFS events observed by 5 yrs since randomization. 60%, 46% and 44% of pts had ≥4 pLNs; 42%, 90% and 92% had chemotherapy. The table summarizes results. Conclusions: In re-analysis of clinical high risk HR+/HER2- subgroups of 3 trials each ̃700 pts, 5 yrs AI vs T had similar magnitude of early trt effects after 2-3 yrs follow-up of all pts vs trt effects observed after 27 mos median follow-up in monarchE trial (HR=0.70; KM diffs 2.7% at 2 yrs, 5.4% at 3 yrs; n=5637). Relative and absolute trt effects sometimes diminished when estimated over 5 yrs rather than over 2 yrs, but meaningful absolute differences remained at 5 yrs in contrast to Penelope-B trial results. Design and interpretation of high risk HR+/HER2- early BC trials may depend on timing of randomization and selection of backbone adjuvant trts; follow-up >5 yrs must remain standard. [Table: see text]

Published
2022
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12. Clinical behavior of recurrent hormone receptor-positive breast cancer by adjuvant endocrine therapy: A Breast International Group (BIG) 1-98 sub-analyses.

Author

Leone, Jose Pablo, primary, Cole, Bernard F., additional, Regan, Meredith M., additional, Thurlimann, Beat J. K., additional, Coates, Alan S., additional, Goldhirsch, Aron, additional, Di Leo, Angelo, additional, Colleoni, Marco, additional, Luis, Ines Maria Vaz Duarte, additional, and Lin, Nancy U., additional

Published
2019
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14. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial

Author

Wapnir, I.L., Price, K.N., Anderson, S.J., Robidoux, A., Martin, M., Nortier, J.W.R., Paterson, A.H.G., Rimawi, M.F., Lang, I., Baena-Canada, J.M., Thurlimann, B., Mamounas, E.P., Geyer, C.E., Gelber, S., Coates, A.S., Gelber, R.D., Rastogi, P., Regan, M.M., Wolmark, N., Aebi, S., NRG Oncology, GEICAM Spanish Breast Canc Grp, BOOG Dutch Breast Canc Trialists G, and Breast Int Grp

Subjects
Oncology, Adult, Cancer Research, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Estrogen receptor, Antineoplastic Agents, Breast Neoplasms, 610 Medicine & health, law.invention, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Randomized controlled trial, law, Internal medicine, medicine, Biomarkers, Tumor, Humans, 030212 general & internal medicine, Progression-free survival, Prospective Studies, Prospective cohort study, Mastectomy, Aged, Aged, 80 and over, Chemotherapy, business.industry, Hazard ratio, Middle Aged, medicine.disease, Progression-Free Survival, Radiation therapy, Receptors, Estrogen, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Radiotherapy, Adjuvant, Neoplasm Recurrence, Local, business
Abstract

Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)–negative ILRR, but additional follow-up was required in ER-positive ILRR. Patients and Methods CALOR was an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomly assigned to receive CT or no CT and stratified by prior CT, hormone receptor status, and location of ILRR. Patients with hormone receptor–positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti–human epidermal growth factor receptor 2 therapy was optional. End points were disease-free survival (DFS), overall survival, and breast cancer-free interval. Results From August 2003 to January 2010, 162 patients were enrolled: 58 with ER-negative and 104 with ER-positive ILRR. At 9 years of median follow-up, 27 DFS events were observed in the ER-negative group and 40 in the ER-positive group. The hazard ratios (HR) of a DFS event were 0.29 (95% CI, 0.13 to 0.67; 10-year DFS, 70% v 34%, CT v no CT, respectively) in patients with ER-negative ILRR and 1.07 (95% CI, 0.57 to 2.00; 10-year DFS, 50% v 59%, respectively) in patients with ER-positive ILRR ( Pinteraction = .013). HRs were 0.29 (95% CI, 0.13 to 0.67) and 0.94 (95% CI, 0.47 to 1.85), respectively, for breast cancer-free interval ( Pinteraction = .034) and 0.48 (95% CI, 0.19 to 1.20) and 0.70 (95% CI, 0.32 to 1.55), respectively, for overall survival ( Pinteraction = .53). Results for the three end points were consistent in multivariable analyses adjusting for location of ILRR, prior CT, and interval from primary surgery. Conclusion The final analysis of CALOR confirms that CT benefits patients with resected ER-negative ILRR and does not support the use of CT for ER-positive ILRR.

Published
2018
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15. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Author

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

Subjects
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

Published
2017
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16. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial

Author

Aebi, S., Gelber, S., Anderson, S.J., Lang, I., Robidoux, A., Martin, M., Nortier, J.W.R., Paterson, A.H.G., Rimawi, M.F., Canada, J.M.B., Thurlimann, B., Murray, E., Mamounas, E.P., Geyer, C.E., Price, K.N., Coates, A.S., Gelber, R.D., Rastogi, P., Wolmark, N., Wapnir, I.L., and CALOR Investigators

Subjects
medicine.medical_specialty, Time Factors, medicine.medical_treatment, Breast Neoplasms, Kaplan-Meier Estimate, Mastectomy, Segmental, Disease-Free Survival, South Africa, Breast cancer, Risk Factors, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Biomarkers, Tumor, medicine, Clinical endpoint, Humans, 610 Medicine & health, Survival rate, Mastectomy, Proportional Hazards Models, business.industry, Patient Selection, Lumpectomy, Australia, Cancer, South America, medicine.disease, Intention to Treat Analysis, Surgery, Europe, Survival Rate, Radiation therapy, Treatment Outcome, Oncology, Chemotherapy, Adjuvant, North America, Disease Progression, Female, Radiotherapy, Adjuvant, Neoplasm Recurrence, Local, business, Febrile neutropenia
Abstract

Summary Background Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. Methods The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti- HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. Findings From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6–6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56–79) with chemotherapy versus 57% (44–67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35–0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (p interaction =0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (p interaction =0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. Interpretation Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. Funding US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Espanol de Investigacion en Cancer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

Published
2014
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19. Adjuvant bisphosphonates in early breast cancer: Consensus guidance for clinical practice from a European Panel

Author

Hadji, P. Coleman, R.E. Wilson, C. Powles, T.J. Clézardin, P. Aapro, M. Costa, L. Body, J.-J. 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, U.-S. Conte, P.-F. Ejlertsen, B. Bergh, J. Kaufmann, M. Holen, I.

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 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.

Published
2016

20. Chemotherapy (CT) for isolated locoregional recurrence (ILRR) of breast cancer in ER-positive (ER+) and ER-negative (ER-) cohorts: Final analysis of the CALOR trial.

Author

Wapnir, Irene, primary, Price, Karen N., additional, Anderson, Stewart J., additional, Robidoux, Andre, additional, Martin, Miguel, additional, Nortier, J. W.R., additional, Paterson, Alexander H. G., additional, Rimawi, Mothaffar F., additional, Lang, Istvan, additional, Baena Cañada, José Manuel, additional, Thurlimann, Beat J. K., additional, Mamounas, Eleftherios P., additional, Geyer, Charles E., additional, Gelber, Shari I., additional, Coates, Alan S., additional, Gelber, Richard D., additional, Rastogi, Priya, additional, Regan, Meredith M., additional, Wolmark, Norman, additional, and Aebi, Stefan Paul, additional

Published
2017
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21. [Is prescription of a therapy costing 150,000 CHF reasonable?]

Author

Solange, Peters, Roger, von Moos, and Beat, Thurlimann

Subjects
Insurance, Health, Prescription Drugs, Patient Selection, Humans, Drug Costs, Health Services Accessibility, Switzerland
Abstract

The costs of medicinal products have increased substantially in the last decade. Access to medical innovations for all patients is in acute danger. This situation requires a political commitment by the wider community of caregivers, healthcare providers and industry. New pricing models are inevitable to garantee access to medical innovation for all people in our society. Further, we must require companies to be more transparent when setting drug prices and require an attitude of consensus on prices between these industries - financially sound. Finally, our health insurance system must accept some state control to avoid patient selection, but also know the precise margin of manoeuvre over time in terms of cost expenditures assigned to oncology.

Published
2015

23. Chemotherapy (CT) for isolated locoregional recurrence (ILRR) of breast cancer in ER-positive (ER+) and ER-negative (ER-) cohorts: Final analysis of the CALOR trial

Author

Mothaffar F. Rimawi, Stewart J. Anderson, Eleftherios P. Mamounas, Alan S. Coates, Beat J. K. Thurlimann, Irene Wapnir, Alexander H. G. Paterson, Miguel Martin, István Láng, Shari I. Gelber, Charles E. Geyer, Norman Wolmark, Stefan Paul Aebi, J. W.R. Nortier, Priya Rastogi, Richard D. Gelber, Meredith M. Regan, José Manuel Baena Cañada, Andre Robidoux, and Karen N. Price

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Chemotherapy, business.industry, medicine.medical_treatment, Endocrine therapy, medicine.disease, ER Negative, Surgery, law.invention, Radiation therapy, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Breast cancer, Randomized controlled trial, law, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, Adjuvant
Abstract

513 Background: ILRR is associated with a high risk of developing breast cancer distant metastases and death. The CALOR trial (NCT00074152) investigated the effectiveness of CT following local therapy for ILRR. Previously reported results at 5-yrs median follow-up (MFU) showed significant benefit of CT for ER- ILRR, but further follow-up was required in ER+ ILRR. This report presents results at 8.8 yrs MFU within ER status cohorts. Methods: CALOR is an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomized to CT (selected by the investigator; multidrug for at least 3 months recommended) or No-CT, and stratified by prior CT, hormone-receptor (ER, PR) status, and location of ILRR. Patients with ER and/or PR positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti-HER2 therapy was optional. Endpoints are disease-free survival (DFS), overall survival (OS) and breast cancer-free interval (BCFI). Results: From August 2003 to January 2010, 162 patients were enrolled: 104 ER+ and 58 ER-. The results at 8.8 years MFU in ER status cohorts are summarized in the Table (40 and 27 DFS events, respectively). The reduction in the hazard of an event associated with CT for the ER- ILRR cohort was sustained, but no benefit was observed for the ER+ cohort; interactions were significant for DFS and BCFI. The reduction in the hazard of an event seen in the ER- cohort was not apparent in ER+, with significant interactions for DFS and BCFI. Results for the 3 endpoints were consistent in multi-variable analyses adjusting for location of ILRR, prior chemotherapy, and interval from primary surgery. Conclusions: The final analysis of CALOR confirms that CT benefits patients with resected ER- ILRR. Long-term CALOR trial results do not support the use of CT for ER+ ILRR. Clinical trial information: NCT00074152. [Table: see text]

Published
2017
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24. Patient-level meta-analysis of randomized trials of aromatase inhibitors (AI) versus tamoxifen (Tam)

Author

Forbes, John F., Mitchell, Dowsett, Rosie, Bradley, Ingle, James N., Tomohiko, Aihara, Bliss, Judith M., Boccardo, Francesco, Coates, Alan S., Charles Coombes, R., Cuzick, Jack M., Peter Christian Dubsky, Michael, Gnant, Manfred, Kaufmann, Kilburn, Lucy S., Francesco, Perrone, Daniel, Rea, Thurlimann, Beat J. K., Van De Velde, Cornelis J. H., Christina, Davies, and Gray, Richard G.

Published
2014

25. Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)dagger

Author

Gourgou-Bourgade, S., Cameron, D., Poortmans, P.M.P., Asselain, B., Azria, D., Cardoso, F., A'Hern, R., Bliss, J., Bogaerts, J., Bonnefoi, H., Brain, E., Cardoso, M.J., Chibaudel, B., Coleman, R., Cufer, T., Lago, L. Dal, Dalenc, F., Azambuja, E. De, Debled, M., Delaloge, S., Filleron, T., Gligorov, J., Gutowski, M., Jacot, W., Kirkove, C., MacGrogan, G., Michiels, S., Negreiros, I., Offersen, B.V., Penault Llorca, F., Pruneri, G., Roche, H., Russell, N.S., Schmitt, F., Servent, V., Thurlimann, B., Untch, M., Hage, J.A. van der, Tienhoven, G. van, Wildiers, H., Yarnold, J., Bonnetain, F., Mathoulin-Pelissier, S., Bellera, C., Dabakuyo-Yonli, T.S., Gourgou-Bourgade, S., Cameron, D., Poortmans, P.M.P., Asselain, B., Azria, D., Cardoso, F., A'Hern, R., Bliss, J., Bogaerts, J., Bonnefoi, H., Brain, E., Cardoso, M.J., Chibaudel, B., Coleman, R., Cufer, T., Lago, L. Dal, Dalenc, F., Azambuja, E. De, Debled, M., Delaloge, S., Filleron, T., Gligorov, J., Gutowski, M., Jacot, W., Kirkove, C., MacGrogan, G., Michiels, S., Negreiros, I., Offersen, B.V., Penault Llorca, F., Pruneri, G., Roche, H., Russell, N.S., Schmitt, F., Servent, V., Thurlimann, B., Untch, M., Hage, J.A. van der, Tienhoven, G. van, Wildiers, H., Yarnold, J., Bonnetain, F., Mathoulin-Pelissier, S., Bellera, C., and Dabakuyo-Yonli, T.S.

Abstract

Item does not contain fulltext, BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

Published
2015

31. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer

Author

Parmar MKB, Torri V, Bonaventura A, Bonazzi C, Colombo N, Delaloye JF, Marsoni S, Mangioni C, Sandercock J, Sessa C, Williams C, Tinazzi A, Flann M, Geiser K, Scorpiglione N, Stewart JF, Chaves J, Palmeiro E, Curtain A, McCormack T, Gennatas C, Marras F, Oppo TG, Balestrino M, Malzoni C, Malzoni M, Belli M, Geminiani ML, Crestani G, Monaco A, Vavala V, Piatto E, Barattini G, Fornara PG, Chetri MC, Santeufemia G, Artioli F, Carone D, Fanizza G, Trentadue R, Priolo D, Scollo P, Nigro SC, Petrina M, Mastrantonio P, Spanna GD, Zagni R, Belloni C, Colleoni R, Redaelli L, Cavagnini A, Di Costanzo G, Perroni D, Arienti S, Orfanotti G, Cantoni FM, Secli R, Bianchi A, Martinello R, Mollica G, Maizzi D, Picchiarelli ME, Fiorini G, Borsani M, Colombo E, Garsia S, Melgrati L, Paggi G, Brunenghi GM, Casini M, Isa L, Algeri R, Prozio G, Belfiore G, Angelini F, D'Aprile M, Moreschi M, Mauri ML, Natale N, Senzani FM, Pavanato G, Poggi G, Garuti G, Luerti M, Cruciani G, Pagano F, Baccolo M, Poddi ER, Bocciolone L, Sabelli MA, Maggi R, Restelli C, D'Antona A, Locatelli MC, Pessi A, Raina A, Chiari S, Gabriele A, Pittelli MR, Iacobelli P, Dogliotti L, Gorzegno G, Musso P, Vegna G, Coco G, Alletti DG, Picciotto F, Lucchese V, Epis A, di Palumbo VS, Drudi G, Ravaioli A, Zampella D, Morandi MG, Gorga G, Zucchelli C, Cariello S, Galletto L, Sussio M, Massacesi L, Massacesi M, Carli A, Tucci E, Tajani E, Corrado G, Bumma S, Durando A, Massobrio M, Sberveglieri M, Biasio M, Guercio E, Jura R, Danese S, Wierdis T, Farnelli C, Tarantino G, Grassi R, Repetti F, Rocchi B, Grampa M, Ercoli A, Griso C, Signori E, Zanini L, Presti M, Klimek M, Urbanski K, Biswas A, Viegas O, Kochli O, Dreher E, Fey M, Beck G, Ludin J, Bonnefoi H, Krauer F, Bauer J, Delmore G, Furrer C, Lorenz U, Thurlimann B, Bronz L, Sanna P, Wyss D, Goldhirsch A, Gyr T, Leidi L, Pastorelli G, Pagani O, Rey P, Hailer U, Benz J, Kaye SB, Reed NS, Symonds RP, Atkinson RJ, Axford AT, Rustin G, Seckl MJ, Green JA, Scott IV, Guthrie D, Harper PG, Calman F, Dobbs HJ, Weir P, Cassoni A, Lederman JA, Souhami RL, Bozzino J, Adab F, Redman CWE, Scoble JE, Paterson M, Daniel F, Cowley N, Williams CJ, Spooner D, Hong A, McIllmurray M, Hendy-Ibbs P, Hall V, Iveson TJ, Whitehouse JMA, Garry R, Lamont A, Robinson A, Trask CW, Clubb AW, Murrell D, Newman G, Wilkins M, Goldthorp WO, Roberts JK, Radstone DJ, Whipp MJ, Ledermann JA, Pater J, Buyse M, Omura G, Parmar, Mkb, Torri, V, Bonaventura, A, Bonazzi, C, Colombo, N, Delaloye, Jf, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, Jf, Chaves, J, Palmeiro, E, Curtain, A, Mccormack, T, Gennatas, C, Marras, F, Oppo, Tg, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, Ml, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, Pg, Chetri, Mc, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, Sc, Petrina, M, Mastrantonio, P, Spanna, Gd, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, Fm, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, Me, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, Gm, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, Ml, Natale, N, Senzani, Fm, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, Er, Bocciolone, L, Sabelli, Ma, Maggi, R, Restelli, C, D'Antona, A, Locatelli, Mc, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, Mr, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, Dg, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, Mg, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, Sb, Reed, N, Symonds, Rp, Atkinson, Rj, Axford, At, Rustin, G, Seckl, Mj, Green, Ja, Scott, Iv, Guthrie, D, Harper, Pg, Calman, F, Dobbs, Hj, Weir, P, Cassoni, A, Lederman, Ja, Souhami, Rl, Bozzino, J, Adab, F, Redman, Cwe, Scoble, Je, Paterson, M, Daniel, F, Cowley, N, Williams, Cj, Spooner, D, Hong, A, Mcillmurray, M, Hendy-Ibbs, P, Hall, V, Iveson, Tj, Whitehouse, Jma, Garry, R, Lamont, A, Robinson, A, Trask, Cw, Clubb, Aw, Murrell, D, Newman, G, Wilkins, M, Goldthorp, Wo, Roberts, Jk, Radstone, Dj, Whipp, Mj, Ledermann, Ja, Pater, J, Buyse, M, and Omura, G

Published
1998

32. ICON2: randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer. ICON Collaborators. International Collaborative Ovarian Neoplasm Study

Author

Parmar, MKB, Torri, V, Bonaventura, A, Bonazzi, C, Delaloye, J, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, J, Chaves, J, Palmeiro, E, Curtain, A, McCormack, T, Gennatas, C, Marras, F, Oppo, T, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, M, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, P, Chetri, M, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, S, Petrina, M, Mastrantonio, P, Spanna, G, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, F, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, M, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, G, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, M, Natale, N, Senzani, F, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, E, Bocciolone, L, Sabelli, M, Maggi, R, Restelli, C, D'Antona, A, Locatelli, M, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, M, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, D, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, M, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, S, Reed, N, Symonds, R, Atkinson, R, Axford, A, Rustin, G, Seckl, M, Green, J, Scott, I, Guthrie, D, Harper, P, Calman, F, Dobbs, H, Weir, P, Cassoni, A, Lederman, J, Souhami, R, Bozzino, J, Adab, F, Redman, C, Scoble, J, Paterson, M, Daniel, F, Cowley, N, Spooner, D, Hong, A, McIllmurray, M, Hendy Ibbs, P, Hall, V, Iveson, T, Whitehouse, J, Garry, R, Lamont, A, Robinson, A, Trask, C, Clubb, A, Murrell, D, Newman, G, Wilkins, M, Goldthorp, W, Roberts, J, Radstone, D, Whipp, M, Ledermann, J, Pater, J, Buyse, M, Omura, G., COLOMBO, NICOLETTA, Parmar, M, Torri, V, Bonaventura, A, Bonazzi, C, Colombo, N, Delaloye, J, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, J, Chaves, J, Palmeiro, E, Curtain, A, Mccormack, T, Gennatas, C, Marras, F, Oppo, T, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, M, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, P, Chetri, M, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, S, Petrina, M, Mastrantonio, P, Spanna, G, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, F, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, M, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, G, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, M, Natale, N, Senzani, F, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, E, Bocciolone, L, Sabelli, M, Maggi, R, Restelli, C, D'Antona, A, Locatelli, M, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, M, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, D, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, M, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, S, Reed, N, Symonds, R, Atkinson, R, Axford, A, Rustin, G, Seckl, M, Green, J, Scott, I, Guthrie, D, Harper, P, Calman, F, Dobbs, H, Weir, P, Cassoni, A, Lederman, J, Souhami, R, Bozzino, J, Adab, F, Redman, C, Scoble, J, Paterson, M, Daniel, F, Cowley, N, Spooner, D, Hong, A, Mcillmurray, M, Hendy Ibbs, P, Hall, V, Iveson, T, Whitehouse, J, Garry, R, Lamont, A, Robinson, A, Trask, C, Clubb, A, Murrell, D, Newman, G, Wilkins, M, Goldthorp, W, Roberts, J, Radstone, D, Whipp, M, Ledermann, J, Pater, J, Buyse, M, and Omura, G

Subjects
Antineoplastic Combined Chemotherapy Protocol, Ovarian Neoplasm, Alopecia, Leukopenia, Middle Aged, Thrombocytopenia, Carboplatin, Antineoplastic Agent, Doxorubicin, Proportional Hazards Model, Female, Survival Analysi, Cisplatin, Cyclophosphamide, Aged, Human
Abstract

A series of meta-analyses of randomised controlled trials raised the question of whether the three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) was more or less effective than optimal-dose single-agent carboplatin for women with advanced ovarian cancer.

Published
1998

33. Capecitabine and vinorelbine as first-line treatment in elderly patients (or =65 years) with metastatic breast cancer. A phase II trial (SAKK 25/99)

Author

D, Hess, D, Koberle, B, Thurlimann, O, Pagani, A, Schonenberger, S, Mattmann, C, Rochlitz, D, Rauch, J C, Schuller, P, Ballabeni, and K, Ribi

Subjects
Aged, 80 and over, Lung Neoplasms, Skin Neoplasms, Maximum Tolerated Dose, Liver Neoplasms, Bone Neoplasms, Breast Neoplasms, Vinorelbine, Vinblastine, Deoxycytidine, Cohort Studies, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols, Disease Progression, Humans, Female, Fluorouracil, Capecitabine, Aged
Abstract

We evaluated previously established regimens of capecitabine plus vinorelbine in older patients with advanced breast cancer stratified for presence versus absence of bone metastases.Patientsor =65 years who had received no prior chemotherapy for advanced breast cancer received up to six 21-day cycles of vinorelbine 20 mg/m(2) i.v. on days 1 + 8 with oral capecitabine on days 1-14 (1,000 vs. 1,250 mg/m(2) daily in patients with vs. without bone involvement).Median age was 72 years in patients with bone metastases (n = 47) and 75 years in patients without bone metastases (n = 23). Response rates were 43% (95% confidence interval, CI, 28.3-58.8) and 57% (95% CI = 34.5-76.8), respectively. Median time to progression was 4.3 (95% CI = 3.5-6.0 months) and 7.0 months (CI = 4.1-8.3), respectively. Neutropenia was the most common toxicity, with grade 3/4 occurring in 43 and 39%, respectively. Pulmonary embolism was seen in 5 and grade 3 thrombosis in 3 patients. Other toxicities were mild to moderate.These regimens of capecitabine and vinorelbine are active and well tolerated in patients with advanced breast canceror =65 years. Response rates were comparable to published results. The lower capecitabine doses appeared appropriate given the advanced age, bone involvement and prior radiotherapy.

Published
2007

34. 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

35. Prevention of symptomatic skeletal events with denosumab administered every 4 weeks versus every 12 weeks: A noninferiority phase III trial (SAKK 96/12, REDUSE).

Author

Templeton, Arnoud J., primary, Stalder, Lukas, additional, Bernhard, Juerg, additional, Brauchli, Peter, additional, Gillessen, Silke, additional, Hayoz, Stefanie, additional, Klingbiel, Dirk, additional, Matter-Walstra, Klazieu, additional, Thurlimann, Beat J. K., additional, and Von Moos, Roger, additional

Published
2014
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37. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer

Author

Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., Thurlimann, B., Paridaens, R., Smith, I., Mauriac, L., Forbes, J.F., Price, K.N., Regan, M.M., Gelber, R.D., Coates, A.S., Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., Thurlimann, B., Paridaens, R., Smith, I., Mauriac, L., Forbes, J.F., Price, K.N., Regan, M.M., Gelber, R.D., and Coates, A.S.

Abstract

BACKGROUND: The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. METHODS: In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor-positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. RESULTS: At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a nonsignificant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P=0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. CONCLUSIONS: Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxife

Published
2009

38. Letrozole compared with tamoxifen for elderly patients with endocrine-responsive early breast cancer: the BIG 1-98 trial

Author

Crivellari, D., Sun, Z., Coates, A.S., Price, K.N., Thurlimann, B., Mouridsen, H., Mauriac, L., Forbes, J.F., Paridaens, R.J., Castiglione-Gertsch, M., Gelber, R.D., Colleoni, M., Lang, I., Del, Mastro L., Gladieff, L., Rabaglio, M., Smith, I.E., Chirgwin, J.H., Goldhirsch, A., Crivellari, D., Sun, Z., Coates, A.S., Price, K.N., Thurlimann, B., Mouridsen, H., Mauriac, L., Forbes, J.F., Paridaens, R.J., Castiglione-Gertsch, M., Gelber, R.D., Colleoni, M., Lang, I., Del, Mastro L., Gladieff, L., Rabaglio, M., Smith, I.E., Chirgwin, J.H., and Goldhirsch, A.

Abstract

PURPOSE: To explore potential differences in efficacy, treatment completion, and adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole for five years in the Breast International Group (BIG) 1-98 trial. METHODS: This report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns of differences in disease-free survival and incidences of AEs according to age. In addition, three categoric age groups were defined: "younger postmenopausal" patients were younger than 65 years (n = 3,127), "older" patients were 65 to 74 years old (n = 1,500), and "elderly" patients were 75 years of age or older (n = 295). RESULTS: Efficacy results for subpopulations defined by age were similar to the overall trial results: Letrozole significantly improved disease-free survival (DFS), the primary end point, compared with tamoxifen. Elderly patients were less likely to complete trial treatment, but at rates that were similar in the two treatment groups. The incidence of bone fractures, observed more often in the letrozole group, did not differ by age. In elderly patients, letrozole had a significantly higher incidence of any grade 3 to 5 protocol-specified non-fracture AE compared with tamoxifen (P = .002), but differences were not significant for thromboembolic or cardiac AEs. CONCLUSION: Adjuvant treatment with letrozole had superior efficacy (DFS) compared with tamoxifen in all age groups. On the basis of a small number of patients older than 75 years (6%), age per se should not unduly affect the choice of adjuvant endocrine therapy Udgivelsesdato: 2008/4/20

Published
2008

39. Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial

Author

Regan, M.M., Lykkesfeldt, A.E., Dell'Orto, P., Curto, B. Del, Henriksen, K.L., Mastropasqua, M.G., Price, K.N., Mery, E., Lacroix-Triki, M., Braye, S., Altermatt, H.J., Gelber, R.D., Castiglione-Gertsch, M., Goldhirsch, A., Gusterson, B.A., Thurlimann, B., Coates, A.S., Viale, G., Rasmussen, Birgitte Bruun, Regan, M.M., Lykkesfeldt, A.E., Dell'Orto, P., Curto, B. Del, Henriksen, K.L., Mastropasqua, M.G., Price, K.N., Mery, E., Lacroix-Triki, M., Braye, S., Altermatt, H.J., Gelber, R.D., Castiglione-Gertsch, M., Goldhirsch, A., Gusterson, B.A., Thurlimann, B., Coates, A.S., Viale, G., and Rasmussen, Birgitte Bruun

Abstract

Background The Breast International Group (BIG) 1-98 trial (a randomised double-blind phase III trial) has shown that letrozole significantly improves disease-free survival (DFS) compared with tamoxifen in postmenopausal women with endocrine-responsive early breast cancer. Our aim was to establish whether the benefit of letrozole versus tamoxifen differs according to the ERBB2 status of tumours. Methods The BIG 1-98 trial consists of four treatment groups that compare 5 years of monotherapy with letrozole or tamoxifen, and sequential administration of one drug for 2 years followed by the other drug for 3 years. Our study includes data from the 4922 patients randomly assigned to the two monotherapy treatment groups (letrozole or tamoxifen for 5 years; 51 months median follow-up [range <1 to 90 months]). A central assessment of oestrogen receptor (ER), progesterone receptor (PgR) and ERBB2 status using paraffin-embedded primary tumour material was possible for 3650 (74%) patients. ER, PgR, and ERBB2 expression were measured by immunohistochemistry (IHC) and ERBB2-positivity was confirmed by fluorescence in-situ hybridisation (FISH). Positive staining in at least 1% of cells was considered to show presence of ER or PgR expression. Tumours were deemed ERBB2-positive if amplified by FISH, or, for the few tumours with unassessable or unavailable FISH results, if they were IHC 3+. Hazard ratios (HR) estimated by Cox modelling were used to compare letrozole with tamoxifen for DFS, which was the primary endpoint, and to assess treatment-by-covariate interactions. The BIG 1-98 trial is registered on the clinical trials site of the US National Cancer institute website http://www.clinicaltrials.gov/ct/show/NCT00004205. Findings By central assessment 7% (257 of 3650) of tumours were classified as ERBB2-positive. In 3533 patients with tumours confirmed to express ER, DFS was poorer in patients with ERBB2-positive tumours (n=239) than in those with ERBB2-negative tumours (n=329

Published
2008

41. Prevention of palmoplantar erythrodysesthesia (PPE) with an antiperspirant in breast cancer patients treated with pegylated liposomal doxorubicin (PLD), a placebo-controlled, double blinded, phase lll trial (SAKK 92/08).

Author

Ruhstaller, Thomas, primary, Ribi, Karin, additional, Sun, Hong, additional, Schmitz, Shu-Fang, additional, Borner, Markus, additional, Winkler, Annette, additional, Mueller, Andreas, additional, von Rohr, Lukas, additional, Winterhalder, Ralph C., additional, Rochlitz, Christoph, additional, Von Moos, Roger, additional, Anchisi, Sandro, additional, Caspar, Clemens B., additional, Zaman, Khalil, additional, Bodmer, Alexandre, additional, Beyeler, Michael, additional, Berardi, Simona, additional, Thurlimann, Beat J. K., additional, and Templeton, Arnoud, additional

Published
2012
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44. BIG 1–98: Randomized double-blind phase III study to evaluate letrozole (L) vs. tamoxifen (T) as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer

Author

Thurlimann, B. J., primary, Keshaviah, A., additional, Mouridsen, H., additional, Mauriac, L., additional, Forbes, J. F., additional, Paridaens, R., additional, Castiglione-Gertsch, M., additional, Gelber, R. D., additional, Smith, I., additional, and Goldhirsch, A., additional

Published
2005
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45. ICON2: Randomised trial of single-agent carboplatin against three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) in women with ovarian cancer

Author

Parmar, M, Torri, V, Bonaventura, A, Bonazzi, C, Colombo, N, Delaloye, J, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, J, Chaves, J, Palmeiro, E, Curtain, A, Mccormack, T, Gennatas, C, Marras, F, Oppo, T, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, M, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, P, Chetri, M, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, S, Petrina, M, Mastrantonio, P, Spanna, G, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, F, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, M, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, G, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, M, Natale, N, Senzani, F, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, E, Bocciolone, L, Sabelli, M, Maggi, R, Restelli, C, D'Antona, A, Locatelli, M, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, M, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, D, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, M, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, S, Reed, N, Symonds, R, Atkinson, R, Axford, A, Rustin, G, Seckl, M, Green, J, Scott, I, Guthrie, D, Harper, P, Calman, F, Dobbs, H, Weir, P, Cassoni, A, Lederman, J, Souhami, R, Bozzino, J, Adab, F, Redman, C, Scoble, J, Paterson, M, Daniel, F, Cowley, N, Spooner, D, Hong, A, Mcillmurray, M, Hendy Ibbs, P, Hall, V, Iveson, T, Whitehouse, J, Garry, R, Lamont, A, Robinson, A, Trask, C, Clubb, A, Murrell, D, Newman, G, Wilkins, M, Goldthorp, W, Roberts, J, Radstone, D, Whipp, M, Ledermann, J, Pater, J, Buyse, M, Omura, G, Parmar, MKB, McCormack, T, McIllmurray, M, Omura, G., COLOMBO, NICOLETTA, Parmar, M, Torri, V, Bonaventura, A, Bonazzi, C, Colombo, N, Delaloye, J, Marsoni, S, Mangioni, C, Sandercock, J, Sessa, C, Williams, C, Tinazzi, A, Flann, M, Geiser, K, Scorpiglione, N, Stewart, J, Chaves, J, Palmeiro, E, Curtain, A, Mccormack, T, Gennatas, C, Marras, F, Oppo, T, Balestrino, M, Malzoni, C, Malzoni, M, Belli, M, Geminiani, M, Crestani, G, Monaco, A, Vavala, V, Piatto, E, Barattini, G, Fornara, P, Chetri, M, Santeufemia, G, Artioli, F, Carone, D, Fanizza, G, Trentadue, R, Priolo, D, Scollo, P, Nigro, S, Petrina, M, Mastrantonio, P, Spanna, G, Zagni, R, Belloni, C, Colleoni, R, Redaelli, L, Cavagnini, A, Di Costanzo, G, Perroni, D, Arienti, S, Orfanotti, G, Cantoni, F, Secli, R, Bianchi, A, Martinello, R, Mollica, G, Maizzi, D, Picchiarelli, M, Fiorini, G, Borsani, M, Colombo, E, Garsia, S, Melgrati, L, Paggi, G, Brunenghi, G, Casini, M, Isa, L, Algeri, R, Prozio, G, Belfiore, G, Angelini, F, D'Aprile, M, Moreschi, M, Mauri, M, Natale, N, Senzani, F, Pavanato, G, Poggi, G, Garuti, G, Luerti, M, Cruciani, G, Pagano, F, Baccolo, M, Poddi, E, Bocciolone, L, Sabelli, M, Maggi, R, Restelli, C, D'Antona, A, Locatelli, M, Pessi, A, Raina, A, Chiari, S, Gabriele, A, Pittelli, M, Iacobelli, P, Dogliotti, L, Gorzegno, G, Musso, P, Vegna, G, Coco, G, Alletti, D, Picciotto, F, Lucchese, V, Epis, A, di Palumbo, V, Drudi, G, Ravaioli, A, Zampella, D, Morandi, M, Gorga, G, Zucchelli, C, Cariello, S, Galletto, L, Sussio, M, Massacesi, L, Massacesi, M, Carli, A, Tucci, E, Tajani, E, Corrado, G, Bumma, S, Durando, A, Massobrio, M, Sberveglieri, M, Biasio, M, Guercio, E, Jura, R, Danese, S, Wierdis, T, Farnelli, C, Tarantino, G, Grassi, R, Repetti, F, Rocchi, B, Grampa, M, Ercoli, A, Griso, C, Signori, E, Zanini, L, Presti, M, Klimek, M, Urbanski, K, Biswas, A, Viegas, O, Kochli, O, Dreher, E, Fey, M, Beck, G, Ludin, J, Bonnefoi, H, Krauer, F, Bauer, J, Delmore, G, Furrer, C, Lorenz, U, Thurlimann, B, Bronz, L, Sanna, P, Wyss, D, Goldhirsch, A, Gyr, T, Leidi, L, Pastorelli, G, Pagani, O, Rey, P, Hailer, U, Benz, J, Kaye, S, Reed, N, Symonds, R, Atkinson, R, Axford, A, Rustin, G, Seckl, M, Green, J, Scott, I, Guthrie, D, Harper, P, Calman, F, Dobbs, H, Weir, P, Cassoni, A, Lederman, J, Souhami, R, Bozzino, J, Adab, F, Redman, C, Scoble, J, Paterson, M, Daniel, F, Cowley, N, Spooner, D, Hong, A, Mcillmurray, M, Hendy Ibbs, P, Hall, V, Iveson, T, Whitehouse, J, Garry, R, Lamont, A, Robinson, A, Trask, C, Clubb, A, Murrell, D, Newman, G, Wilkins, M, Goldthorp, W, Roberts, J, Radstone, D, Whipp, M, Ledermann, J, Pater, J, Buyse, M, Omura, G, Parmar, MKB, McCormack, T, McIllmurray, M, Omura, G., and COLOMBO, NICOLETTA

Abstract

A series of meta-analyses of randomised controlled trials raised the question of whether the three-drug combination of CAP (cyclophosphamide, doxorubicin, and cisplatin) was more or less effective than optimal-dose single-agent carboplatin for women with advanced ovarian cancer.

Published
1998

49. Duration of adjuvant chemotherapy for breast cancer: a joint analysis of two randomised trials investigating three versus six courses of CMF.

Author

Colleoni, M., Litman, H.J., Castiglione-Gertsch, M., Sauerbrei, W., Gelber, R.D., Boneti, M., Coates, A.S., Schumacher, M., Bastert, G., Rudenstam, C.-M., Schmoor, C., Lindtner, J., Collins, J., Thurlimann, B., Holmberg, S.B., Crivellari, D., Beyerle, C., Neumann, R.L.A., Goldhirsch, A., and Bonetti, M

Subjects
BREAST cancer treatment, ADJUVANT treatment of cancer, METHOTREXATE, FLUOROURACIL, THERAPEUTIC use of antineoplastic agents, ADJUVANT chemotherapy, SURVIVAL, PERIMENOPAUSE, CLINICAL trials, TIME, ANTINEOPLASTIC agents, PROGNOSIS, DRUG administration, RANDOMIZED controlled trials, CYCLOPHOSPHAMIDE, RESEARCH funding, MENOPAUSE, BREAST tumors
Abstract

Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive 'classical' cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (+/-s.e.) were 54+/-2% for three cycles and 55+/-2% for six cycles (n=1024; risk ratio (risk ratio: CMFx3/CMFx6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation. [ABSTRACT FROM AUTHOR]

Published
2002

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