Breast cancer - null regimens

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main breast cancer page for regimens that include active anticancer treatment.
=Adjuvant therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Lacour et al. 1980 	1972-1979 	Phase 3 (C) 	Polya.Polyu 	Might have shorter OS
Bonadonna et al. 1976 	1973-1975 	Phase 3 (C) 	CMF 	Shorter RFS
Rubens et al. 1983 	1975-1979 	Phase 3 (C) 	Melphalan 	Might have shorter RFS
Clahsen et al. 1995 (EORTC 09771) 	1976-1980 	Phase 3 (C) 	CMF; 700/30/700 x 24 	Seems to have shorter OS
Howell et al. 1984 	1976-1983 	Phase 3 (C) 	CMF; 1120/64/960 x 12	Shorter RFS
Brinker et al. 1983 (DBCG 77B) 	1977-1983 	Phase 3 (C) 	1. CMF 	Seems to have shorter OS1
Brinker et al. 1983 (DBCG 77B) 	1977-1983 	Phase 3 (C) 	2. Cyclophosphamide 	Seems to have shorter OS1
Brinker et al. 1983 (DBCG 77B) 	1977-1983 	Phase 3 (C) 	3. Levamisole 	Did not meet co-primary endpoints of IDFS/OS
Goldhirsch et al. 1984 (LBCS III) 	1978-1981 	Phase 3 (C) 	1. CMFPT 	Shorter DFS
Goldhirsch et al. 1984 (LBCS III) 	1978-1981 	Phase 3 (C) 	2. PT 	Shorter DFS
Goldhirsch et al. 1984 (LBCS IV) 	1978-1981 	Phase 3 (C) 	PT 	Seems to have shorter DFS
Fisher et al. 1989 (NSABP B-13) 	1981-1988 	Phase 3 (C) 	MF; sequential 	Shorter DFS2
Mansour et al. 1989 (ECOG E1180) 	1981-1988 	Phase 3 (C) 	CMFP 	Shorter DFS
Jakesz et al. 1998 	1984-1990 	Phase 3 (C) 	AV-CMF 	Did not meet primary endpoint of DFS60
Héry et al. 2006 (FASG 03) 	1988-1994 	Phase 3 (C) 	FEC50 x 6 	Did not meet primary endpoint of DFS120
Amadori et al. 2000 	1989-1993 	Phase 3 (C) 	CMF x 6 	Seems to have shorter DFS
Paradiso et al. 2001 	1989-1994 	Phase 3 (C) 	FEC x 6 	Shorter DFS (primary endpoint)DFS60: 69% vs 81%(HR 1.72, 95% CI 1.06-3.33)
Arriagada et al. 2005 	1989-1996 	Phase 3 (C) 	FEC50 x 6 	Shorter DFS
Hortobagyi et al. 2000 	1990-1997 	Randomized (C)	CEP with auto HSCT 	Did not meet primary endpoint of DFS
Adjuvant Breast Cancer Trials Collaborative Group 2007 (NCRI ABC-CT)	1992-2000 	Phase 3 (C) 	CMF; 1400/80/1200 x 6	Seems to have shorter OS
Mamounas et al. 2005 (NSABP B-28) 	1995-1998 	Phase 3 (C) 	Paclitaxel; q3wk 	Shorter DFS
Colleoni et al. 2016 (IBCSG 22-00) 	2000-2012 	Phase 3 (C) 	CM 	Did not meet primary endpoint of DFS
Aebi et al. 2014 (CALOR) 	2003-2010 	Phase 3 (C) 	Chemotherapy 	Seems to have shorter DFS
1Reported efficacy for DBCG 77B is based on the 2010 update.
2Reported efficacy for NSABP B-13 is based on the 1996 update.
Note: No further systemic treatment; many of these trials incorporated RT, however (see individual papers for details). Jakesz et al. 1998 was conducted prior to routine testing of HER2, so it technically included "double-negative" patients. ECOG E1180 is also known as INT-0011.
====Preceding treatment====
*Bonadonna et al. 1976: Mastectomy
*ECOG E1180: Modified radical mastectomy or total mastectomy with low axillary-node dissection
*NSABP B-28: Surgery, then adjuvant AC x 4
*Jakesz et al. 1998: Surgery
*IBCSG 22-00: Surgery, then adjuvant chemotherapy
===References===
# Bonadonna G, Brusamolino E, Valagussa P, Rossi A, Brugnatelli L, Brambilla C, De Lena M, Tancini G, Bajetta E, Musumeci R, Veronesi U. Combination chemotherapy as an adjuvant treatment in operable breast cancer. N Engl J Med. 1976 Feb 19;294(8):405-10. link to original article EuroPMC
## Update: Bonadonna G, Rossi A, Valagussa P, Banfi A, Veronesi U. The CMF program for operable breast cancer with positive axillary nodes: updated analysis on the disease-free interval, site of relapse and drug tolerance. Cancer. 1977 Jun;39(6 Suppl):2904-15. link to original article EuroPMC
## Update: Bonadonna G, Valagussa P, Rossi A, Tancini G, Brambilla C, Zambetti M, Veronesi U. Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat. 1985;5(2):95-115. link to original article EuroPMC
## Update: Bonadonna G, Valagussa P, Moliterni A, Zambetti M, Brambilla C. Adjuvant cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer: the results of 20 years of follow-up. N Engl J Med. 1995 Apr 6;332(14):901-6. link to original article EuroPMC
# Lacour J, Lacour F, Spira A, Michelson M, Petit JY, Delage G, Sarrazin D, Contesso G, Viguier J. Adjuvant treatment with polyadenylic-polyuridylic acid (Polya-Polyu) in operable breast cancer. Lancet. 1980 Jul 26;2(8187):161-4. link to original article EuroPMC
# Rubens RD, Hayward JL, Knight RK, Bulbrook RD, Fentiman IS, Chaudary M, Howell A, Bush H, Crowther D, Sellwood RA, George WD, Howat JM. Controlled trial of adjuvant chemotherapy with melphalan for breast cancer. Lancet. 1983 Apr 16;1(8329):839-43. link to original article EuroPMC
# DBCG 77B: Brincker H, Mouridsen HT, Andersen KW. Adjuvant chemotherapy with cyclophosphamide or CMF in premenopausal women with stage II breast cancer. Breast Cancer Res Treat. 1983;3(1):91-5. link to original article EuroPMC
## Update: Ejlertsen B, Mouridsen HT, Jensen MB, Andersen J, Andersson M, Kamby C, Knoop AS; Danish Breast Cancer Cooperative Group. Cyclophosphamide, methotrexate, and fluorouracil; oral cyclophosphamide; levamisole; or no adjuvant therapy for patients with high-risk, premenopausal breast cancer. Cancer. 2010 May 1;116(9):2081-9. link to original article EuroPMC
# LBCS III/IV: Goldhirsch A; Ludwig Breast Cancer Study Group. Randomised trial of chemo-endocrine therapy, endocrine therapy, and mastectomy alone in postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet. 1984 Jun 9;1(8389):1256-60. link to original article EuroPMC
# Howell A, Bush H, George WD, Howat JM, Crowther D, Sellwood RA, Rubens RD, Hayward JL, Bulbrook RD, Fentiman IS, Chaudary M. Controlled trial of adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil for breast cancer. Lancet. 1984 Aug 11;2(8398):307-11. link to original article EuroPMC
# NSABP B-13: Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, Glass A, Foster R, Caplan R. A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med. 1989 Feb 23;320(8):473-8. link to original article EuroPMC
## Update: Fisher B, Dignam J, Mamounas EP, Costantino JP, Wickerham DL, Redmond C, Wolmark N, Dimitrov NV, Bowman DM, Glass AG, Atkins JN, Abramson N, Sutherland CM, Aron BS, Margolese RG. Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol. 1996 Jul;14(7):1982-92. link to original article EuroPMC
## Update: Fisher B, Jeong JH, Anderson S, Wolmark N. Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst. 2004 Dec 15;96(24):1823-31. link to original article EuroPMC
## Pooled update: Taghian AG, Jeong JH, Mamounas EP, Parda DS, Deutsch M, Costantino JP, Wolmark N. Low locoregional recurrence rate among node-negative breast cancer patients with tumors 5 cm or larger treated by mastectomy, with or without adjuvant systemic therapy and without radiotherapy: results from five national surgical adjuvant breast and bowel project randomized clinical trials. J Clin Oncol. 2006 Aug 20;24(24):3927-32. link to original article EuroPMC
# ECOG E1180: Mansour EG, Gray R, Shatila AH, Osborne CK, Tormey DC, Gilchrist KW, Cooper MR, Falkson G. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med. 1989 Feb 23;320(8):485-90. link to original article EuroPMC
# LCBS V: Goldhirsch A, Gelber RD; Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med. 1989 Feb 23;320(8):491-6. link to original article EuroPMC
# EORTC 09771: Clahsen PC, van de Velde CJ, Welvaart K, Repelaer van Driel OJ, Sylvester RJ; Cooperating Investigators. Ten-year results of a randomized trial evaluating prolonged low-dose adjuvant chemotherapy in node-positive breast cancer: a joint European Organisation for Research and Treatment of Cancer-Dutch Breast Cancer Working Party Study. J Clin Oncol. 1995 Jan;13(1):33-41. link to original article EuroPMC
# Jakesz R, Samonigg H, Gnant M, Kubista E, Steindorfer P, Hausmaninger H, Sevelda P, Tschurtschenthaler B, Fridrik M, Stierer M, Kolb R, Steger G; Austrian Breast Cancer Study Group. Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Eur J Cancer. 1998 Jan; 34 (1): 66-70. link to original article EuroPMC
# Hortobagyi GN, Buzdar AU, Theriault RL, Valero V, Frye D, Booser DJ, Holmes FA, Giralt S, Khouri I, Andersson B, Gajewski JL, Rondon G, Smith TL, Singletary SE, Ames FC, Sneige N, Strom EA, McNeese MD, Deisseroth AB, Champlin RE. Randomized trial of high-dose chemotherapy and blood cell autografts for high-risk primary breast carcinoma. J Natl Cancer Inst. 2000 Feb 2;92(3):225-33. link to original article EuroPMC
# Amadori D, Nanni O, Marangolo M, Pacini P, Ravaioli A, Rossi A, Gambi A, Catalano G, Perroni D, Scarpi E, Giunchi DC, Tienghi A, Becciolini A, Volpi A. Disease-free survival advantage of adjuvant cyclophosphamide, methotrexate, and fluorouracil in patients with node-negative, rapidly proliferating breast cancer: a randomized multicenter study. J Clin Oncol. 2000 Sep;18(17):3125-34. link to original article EuroPMC
## Update: Amadori D, Nanni O, Volpi A, Casadei Giunchi D, Marangolo M, Livi L, Ravaioli A, Rossi AP, Gambi A, Luzi Fedeli S, Perroni D, Scarpi E, Becciolini A, Silvestrini R. Phase III randomized multicenter study on the effects of adjuvant CMF in patients with node-negative, rapidly proliferating breast cancer: twelve-year results and retrospective subgroup analysis. Breast Cancer Res Treat. 2008 Mar;108(2):259-64. Epub 2007 May 26. link to original article EuroPMC
# Paradiso A, Schittulli F, Cellamare G, Mangia A, Marzullo F, Lorusso V, De Lena M. Randomized clinical trial of adjuvant fluorouracil, epirubicin, and cyclophosphamide chemotherapy for patients with fast-proliferating, node-negative breast cancer. J Clin Oncol. 2001 Oct 1;19(19):3929-37. link to original article EuroPMC
# NSABP B-28: Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher B, Wickerham DL, Yothers G, Soran A, Wolmark N. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96. Epub 2005 May 16. link to original article EuroPMC
# Arriagada R, Spielmann M, Koscielny S, Le Chevalier T, Delozier T, Rémé-Saumon M, Ducourtieux M, Tursz T, Hill C. Results of two randomized trials evaluating adjuvant anthracycline-based chemotherapy in 1146 patients with early breast cancer. Acta Oncol. 2005;44(5):458-66. link to original article EuroPMC
# FASG 03: Héry M, Bonneterre J, Roché H, Luporsi E, Kerbrat P, Namer M, Fumoleau P, Monnier A, Fargeot P. Epirubicin-based chemotherapy as adjuvant treatment for poor prognosis, node-negative breast cancer: 10-year follow-up results of the French Adjuvant Study Group 03 trial. Bull Cancer. 2006 Oct;93(10):E109-14. link to original article EuroPMC
# NCRI ABC-CT: Adjuvant Breast Cancer Trials Collaborative Group. Polychemotherapy for early breast cancer: results from the international adjuvant breast cancer chemotherapy randomized trial. J Natl Cancer Inst. 2007 Apr 4;99(7):506-15. link to original article EuroPMC NCT00002582
#CALOR: Aebi S, Gelber S, Anderson SJ, Láng I, Robidoux A, Martín M, Nortier JW, Paterson AH, Rimawi MF, Cañada JM, Thürlimann B, Murray E, Mamounas EP, Geyer CE Jr, Price KN, Coates AS, Gelber RD, Rastogi P, Wolmark N, Wapnir IL; CALOR investigators. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol. 2014 Feb;15(2):156-63. Epub 2014 Jan 16. link to original article link to PMC article EuroPMC NCT00074152
##Update: Wapnir IL, Price KN, Anderson SJ, Robidoux A, Martín M, Nortier JWR, Paterson AHG, Rimawi MF, Láng I, Baena-Cañada JM, Thürlimann B, Mamounas EP, Geyer CE Jr, Gelber S, Coates AS, Gelber RD, Rastogi P, Regan MM, Wolmark N, Aebi S; International Breast Cancer Study Group; NRG Oncology; GEICAM Spanish Breast Cancer Group; BOOG Dutch Breast Cancer Trialists' Group; Breast International Group. Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial. J Clin Oncol. 2018 Apr 10;36(11):1073-1079. Epub 2018 Feb 14. link to original article link to PMC article EuroPMC
# IBCSG 22-00: Colleoni M, Gray KP, Gelber S, Láng I, Thürlimann B, Gianni L, Abdi EA, Gomez HL, Linderholm BK, Puglisi F, Tondini C, Kralidis E, Eniu A, Cagossi K, Rauch D, Chirgwin J, Gelber RD, Regan MM, Coates AS, Price KN, Viale G, Goldhirsch A. Low-dose oral cyclophosphamide and methotrexate maintenance for hormone receptor-negative early breast cancer: International Breast Cancer Study Group trial 22-00. J Clin Oncol. 2016 Oct 1;34(28):3400-8. Epub 2016 Jun 20. link to original article link to PMC article EuroPMC NCT00022516
#SWOG S1418: NCT02954874
==Placebo==
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator	Comparative Efficacy
Fisher et al. 1968 (NSABP B-01) 	1958-1961 	Phase 3 (C)	Thiotepa 	Did not meet primary endpoint of RR
Fisher et al. 1975 (NSABP B-05) 	1972-1974 	Phase 3 (C)	Melphalan 	Might have shorter DFS1
Paterson et al. 2012 (NSABP B-34) 	2001-2004 	Phase 3 (C)	Clodronate	Did not meet primary endpoint of DFS
Coombes et al. 2021 (REACT) 	2007-2012 	Phase 3 (C)	Celecoxib 	Did not meet primary endpoint of DFS
Coleman et al. 2019 (D-CARE) 	2010-2012 	Phase 3 (C)	Denosumab 	Did not meet composite primary endpoint of bone MFS
Goodwin et al. 2022 (NCIC CTG MA.32)	2010-2013 	Phase 3 (C)	Metformin 	Did not meet primary endpoint of IDFS
Tutt et al. 2021 (OlympiA) 	2014-2019 	Phase 3 (C)	Olaparib 	Shorter OS2
Chen et al. 2024 (Alliance A011502) 	2017-01-06 to 2020-12-04	Phase 3 (C)	Aspirin 	Might have longer iDFS (primary endpoint)(HR 0.79, 95% CI 0.61-1.01)
1Reported efficacy for NSABP B-05 is based on the 1986 update.
2Reported efficacy for OlympiA is based on the 2022 update.
No active antineoplastic treatment within the study design. Used as a comparator arm. Note that some trials do have other ongoing antineoplastic treatments outside of the study design, such as adjuvant radiation therapy.
====Preceding treatment====
*NSABP B-05: Mastectomy
===References===
# NSABP B-01: Fisher B, Ravdin RG, Ausman RK, Slack NH, Moore GE, Noer RJ. Surgical adjuvant chemotherapy in cancer of the breast: results of a decade of cooperative investigation. Ann Surg. 1968 Sep;168(3):337-56. link to original article link to PMC article EuroPMC
## Update: Fisher B, Slack N, Katrych D, Wolmark N. Ten year follow-up results of patients with carcinoma of the breast in a co-operative clinical trial evaluating surgical adjuvant chemotherapy. Surg Gynecol Obstet. 1975 Apr;140(4):528-34. EuroPMC
# NSABP B-05: Fisher B, Carbone P, Economou SG, Frelick R, Glass A, Lerner H, Redmond C, Zelen M, Band P, Katrych DL, Wolmark N, Fisher ER. 1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer: a report of early findings. N Engl J Med. 1975 Jan 16;292(3):117-22. link to original article EuroPMC
## Update: Fisher B, Glass A, Redmond C, Fisher ER, Barton B, Such E, Carbone P, Economou S, Foster R, Frelick R, Lerner H, Levitt M, Margolese R, MacFarlane J, Plotkin D, Shibata H, Volk H. L-phenylalanine mustard (L-PAM) in the management of primary breast cancer: an update of earlier findings and a comparison with those utilizing L-PAM plus 5-fluorouracil (5-FU). Cancer. 1977 Jun;39(6 Suppl):2883-903. link to original article EuroPMC
## Update: Fisher B, Fisher ER, Redmond C. Ten-year results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trial evaluating the use of L-phenylalanine mustard (L-PAM) in the management of primary breast cancer. J Clin Oncol. 1986 Jun;4(6):929-41. link to original article EuroPMC
# NSABP B-34: Paterson AH, Anderson SJ, Lembersky BC, Fehrenbacher L, Falkson CI, King KM, Weir LM, Brufsky AM, Dakhil S, Lad T, Baez-Diaz L, Gralow JR, Robidoux A, Perez EA, Zheng P, Geyer CE Jr, Swain SM, Costantino JP, Mamounas EP, Wolmark N. Oral clodronate for adjuvant treatment of operable breast cancer (National Surgical Adjuvant Breast and Bowel Project protocol B-34): a multicentre, placebo-controlled, randomised trial. Lancet Oncol. 2012 Jul;13(7):734-42. Epub 2012 Jun 14. link to original article link to PMC article EuroPMC NCT00009945
# D-CARE: Coleman R, Finkelstein DM, Barrios C, Martin M, Iwata H, Hegg R, Glaspy J, Periañez AM, Tonkin K, Deleu I, Sohn J, Crown J, Delaloge S, Dai T, Zhou Y, Jandial D, Chan A. Adjuvant denosumab in early breast cancer (D-CARE): an international, multicentre, randomised, controlled, phase 3 trial. Lancet Oncol. 2020 Jan;21(1):60-72. Epub 2019 Dec 2. link to original article EuroPMC NCT01077154
# OlympiA: Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, Gelber RD, de Azambuja E, Fielding A, Balmaña J, Domchek SM, Gelmon KA, Hollingsworth SJ, Korde LA, Linderholm B, Bandos H, Senkus E, Suga JM, Shao Z, Pippas AW, Nowecki Z, Huzarski T, Ganz PA, Lucas PC, Baker N, Loibl S, McConnell R, Piccart M, Schmutzler R, Steger GG, Costantino JP, Arahmani A, Wolmark N, McFadden E, Karantza V, Lakhani SR, Yothers G, Campbell C, Geyer CE Jr; OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021 Jun 24;384(25):2394-2405. Epub 2021 Jun 3. link to original article link to PMC article EuroPMC NCT02032823
##Update: Geyer CE Jr, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, Rastogi P, Cui K, Arahmani A, Aktan G, Armstrong AC, Arnedos M, Balmaña J, Bergh J, Bliss J, Delaloge S, Domchek SM, Eisen A, Elsafy F, Fein LE, Fielding A, Ford JM, Friedman S, Gelmon KA, Gianni L, Gnant M, Hollingsworth SJ, Im SA, Jager A, Jóhannsson ÓÞ, Lakhani SR, Janni W, Linderholm B, Liu TW, Loman N, Korde L, Loibl S, Lucas PC, Marmé F, Martinez de Dueñas E, McConnell R, Phillips KA, Piccart M, Rossi G, Schmutzler R, Senkus E, Shao Z, Sharma P, Singer CF, Španić T, Stickeler E, Toi M, Traina TA, Viale G, Zoppoli G, Park YH, Yerushalmi R, Yang H, Pang D, Jung KH, Mailliez A, Fan Z, Tennevet I, Zhang J, Nagy T, Sonke GS, Sun Q, Parton M, Colleoni MA, Schmidt M, Brufsky AM, Razaq W, Kaufman B, Cameron D, Campbell C, Tutt ANJ; OlympiA Clinical Trial Steering Committee and Investigators. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022 Dec 1;33(12):1250-1268. Epub 2022 Oct 10. link to original article link to PMC article EuroPMC
##PRO analysis: Ganz PA, Bandos H, Španić T, Friedman S, Müller V, Kuemmel S, Delaloge S, Brain E, Toi M, Yamauchi H, de Dueñas EM, Armstrong A, Im SA, Song CG, Zheng H, Sarosiek T, Sharma P, Geng C, Fu P, Rhiem K, Frauchiger-Heuer H, Wimberger P, t'Kint de Roodenbeke D, Liao N, Goodwin A, Chakiba-Brugère C, Friedlander M, Lee KS, Giacchetti S, Takano T, Henao-Carrasco F, Virani S, Valdes-Albini F, Domchek SM, Bane C, McCarron EC, Mita M, Rossi G, Rastogi P, Fielding A, Gelber RD, Scheepers ED, Cameron D, Garber J, Geyer CE, Tutt ANJ. Patient-Reported Outcomes in OlympiA: A Phase III, Randomized, Placebo-Controlled Trial of Adjuvant Olaparib in gBRCA1/2 Mutations and High-Risk Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer. J Clin Oncol. 2024 Apr 10;42(11):1288-1300. Epub 2024 Feb 1. link to original article link to PMC article EuroPMC
#REACT: Coombes RC, Tovey H, Kilburn L, Mansi J, Palmieri C, Bartlett J, Hicks J, Makris A, Evans A, Loibl S, Denkert C, Murray E, Grieve R, Coleman R, Borley A, Schmidt M, Rautenberg B, Kunze CA, Rhein U, Mehta K, Mousa K, Dibble T, Lu XL, von Minckwitz G, Bliss JM; Randomized European Celecoxib Trial (REACT) Trial Management Group and Investigators. Effect of Celecoxib vs Placebo as Adjuvant Therapy on Disease-Free Survival Among Patients With Breast Cancer: The REACT Randomized Clinical Trial. JAMA Oncol. 2021 Sep 1;7(9):1291-1301. link to original article link to PMC article EuroPMC NCT02429427
#NCIC CTG MA.32: Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J, Ligibel JA, Hershman DL, Mayer IA, Hobday TJ, Bliss JM, Rastogi P, Rabaglio-Poretti M, Mukherjee SD, Mackey JR, Abramson VG, Oja C, Wesolowski R, Thompson AM, Rea DW, Stos PM, Shepherd LE, Stambolic V, Parulekar WR. Effect of Metformin vs Placebo on Invasive Disease-Free Survival in Patients With Breast Cancer: The MA.32 Randomized Clinical Trial. JAMA. 2022 May 24;327(20):1963-1973. link to original article link to PMC article EuroPMC NCT01101438
#Alliance A011502: Chen WY, Ballman KV, Partridge AH, Hahn OM, Briccetti FM, Irvin WJ, Symington B, Visvanathan K, Pohlmann PR, Openshaw TH, Weiss A, Winer EP, Carey LA, Holmes MD. Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer: The Alliance A011502 Randomized Trial. JAMA. 2024 May 28;331(20):1714-1721. Epub 2024 Apr 29. link to original article link to PMC article EuroPMC NCT02927249
=Metastatic disease, maintenance after first-line therapy=
==Observation==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Falkson et al. 1998 (INT-0077) 	1982-1992 	Phase 3 (C)	CMF(P)TH 	Shorter RFS
Sparano et al. 2004 (ECOG E2196) 	1997-2001 	Phase 3 (C)	Marimastat	Did not meet primary endpoint of PFS
Alba et al. 2010 (GEICAM 2001-01)	2002-2007 	Phase 3 (C)	PLD x 6 	Shorter TTP
Park et al. 2013 (KCSG-BR07-02) 	2007-2010 	Phase 3 (C)	PG 	Seems to have shorter OSMedian OS: 23.5 vs 32.3 mo(HR 1.54, 95% CI 1.01-2.38)
No further treatment.
====Preceding treatment====
*ECOG E2196: First-line doxorubicin- and/or taxane-containing chemotherapy x 6-8
*GEICAM 2001-01: First-line A-D
*KCSG-BR07-02: First-line PG x 6
===References===
# INT-0077: Falkson G, Gelman RS, Pandya KJ, Osborne CK, Tormey D, Cummings FJ, Sledge GW, Abeloff MD. Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment. J Clin Oncol. 1998 May;16(5):1669-76. link to original article EuroPMC
# ECOG E2196: Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE. Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. link to original article EuroPMC NCT00003010
# GEICAM 2001-01: Alba E, Ruiz-Borrego M, Margelí M, Rodríguez-Lescure A, Sánchez-Rovira P, Ruiz A, Mel-Lorenzo JR, Ramos-Vázquez M, Ribelles N, Calvo E, Casado A, Márquez A, Vicente D, García-Sáenz JA, Martín M. Maintenance treatment with pegylated liposomal doxorubicin versus observation following induction chemotherapy for metastatic breast cancer: GEICAM 2001-01 study. Breast Cancer Res Treat. 2010 Jul;122(1):169-76. Epub 2010 Apr 2. link to original article EuroPMC NCT00128778
# KCSG-BR07-02: Park YH, Jung KH, Im SA, Sohn JH, Ro J, Ahn JH, Kim SB, Nam BH, Oh DY, Han SW, Lee S, Park IH, Lee KS, Kim JH, Kang SY, Lee MH, Park HS, Ahn JS, Im YH. Phase III, multicenter, randomized trial of maintenance chemotherapy versus observation in patients with metastatic breast cancer after achieving disease control with six cycles of gemcitabine plus paclitaxel as first-line chemotherapy: KCSG-BR07-02. J Clin Oncol. 2013 May 10;31(14):1732-9. Epub 2013 Apr 8. link to original article EuroPMC NCT00561119
Category:Breast cancer regimens
Category:Null regimens
Category:Disease-specific pages
Category:Malignant breast neoplasm