Prolonged cyclic combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil was evaluated as adjuvant treatment to radical mastectomy in primary breast cancer with positive axillary lymph nodes. After 27 months of study, treatment occurred in 24 per cent of 179 control patients and in 5.3 per cent of 207 women given combination chemotherapy (P less than 10(-6)), the advantage appearing statistically significant in all subgroups of patients. Patients with four or more positive axillary nodes had a higher per cent of relapses than those with fewer nodes. The initial new clinical manifestations occurred in distant sites in 81.5 per cent of relapsed patients. Long-term chemotherapy produced an acceptable toxicity, thus allowing the administration of a high percentage of drug dosage. These results should be considered with caution, since, at present, the effect of this therapy on survival and possible long-term side effects remain unknown.
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[Full Text]
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(2007). A dose escalation trial of adjuvant cyclophosphamide and epirubicin in combination with 5-fluorouracil using G-CSF support for premenopausal women with breast cancer involving four or more positive nodes. Ann Oncol
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[Abstract][Full Text]
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(2007). Polychemotherapy for Early Breast Cancer: Results From the International Adjuvant Breast Cancer Chemotherapy Randomized Trial. JNCI J Natl Cancer Inst
99: 506-515
[Abstract][Full Text]
Dittrich, C., Petruzelka, L., Vodvarka, P., Gneist, M., Janku, F., Kysela, T., Melemed, A., Latz, J., Simms, L., Krejcy, K.
(2006). A Phase I Study of Pemetrexed (ALIMTA) and Cyclophosphamide in Patients with Locally Advanced or Metastatic Breast Cancer. Clin. Cancer Res.
12: 7071-7078
[Abstract][Full Text]
Levine, M. N., Whelan, T.
(2006). Adjuvant Chemotherapy for Breast Cancer -- 30 Years Later. NEJM
355: 1920-1922
[Full Text]
Feuer, E. J.
(2006). Chapter 1: Modeling the Impact of Adjuvant Therapy and Screening Mammography on U.S. Breast Cancer Mortality Between 1975 and 2000: Introduction to the Problem. J Natl Cancer Inst Monogr
2006: 2-6
[Full Text]
Gilbert, S. G., Banna, G. L., Santoro, A., Gounaris, I. G., Katsumata, M., Drebin, J. A., Greene, M. I., Mastrianni, D. M., Mano, M., Cameron, D., Gelber, R. D., the HERA Trial Study Team, , Bryant, J., Romond, E., Perez, E. A., Hortobagyi, G. N., Barron, H.
(2006). Trastuzumab in breast cancer.. NEJM
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[Full Text]
Hutchins, L. F., Green, S. J., Ravdin, P. M., Lew, D., Martino, S., Abeloff, M., Lyss, A. P., Allred, C., Rivkin, S. E., Osborne, C. K.
(2005). Randomized, Controlled Trial of Cyclophosphamide, Methotrexate, and Fluorouracil Versus Cyclophosphamide, Doxorubicin, and Fluorouracil With and Without Tamoxifen for High-Risk, Node-Negative Breast Cancer: Treatment Results of Intergroup Protocol INT-0102. JCO
23: 8313-8321
[Abstract][Full Text]
Gluck, S.
(2005). Adjuvant Chemotherapy for Early Breast Cancer: Optimal Use of Epirubicin. The Oncologist
10: 780-791
[Abstract][Full Text]
Lin, Y.-C., Chen, S.-C., Chang, H.-K., Hsueh, S., Tsai, C.-S., Lo, Y.-F., Hwang, T.-L., Chen, M.-F.
(2005). Identifying Good Prognosis Group of Breast Cancer Patients with 1-3 Positive Axillary Nodes for Adjuvant Cyclophosphamide, Methotrexate and 5-Fluorouracil (CMF) Chemotherapy. Jpn J Clin Oncol
35: 514-519
[Abstract][Full Text]
Davidson, N. E., O'Neill, A. M., Vukov, A. M., Osborne, C. K., Martino, S., White, D. R., Abeloff, M. D.
(2005). Chemoendocrine Therapy for Premenopausal Women With Axillary Lymph Node-Positive, Steroid Hormone Receptor-Positive Breast Cancer: Results From INT 0101 (E5188). JCO
23: 5973-5982
[Abstract][Full Text]
Levine, M. N., Pritchard, K. I., Bramwell, V. H.C., Shepherd, L. E., Tu, D., Paul, N.
(2005). Randomized Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With Cyclophosphamide, Methotrexate, and Fluorouracil in Premenopausal Women With Node-Positive Breast Cancer: Update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. JCO
23: 5166-5170
[Abstract][Full Text]
Dellapasqua, S., Colleoni, M., Gelber, R. D., Goldhirsch, A.
(2005). Adjuvant Endocrine Therapy for Premenopausal Women With Early Breast Cancer. JCO
23: 1736-1750
[Full Text]
Arriagada, R., Le, M. G., Spielmann, M., Mauriac, L., Bonneterre, J., Namer, M., Delozier, T., Hill, C., Tursz, T.
(2005). Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy. Ann Oncol
16: 389-396
[Abstract][Full Text]
Bonadonna, G., Moliterni, A., Zambetti, M., Daidone, M. G., Pilotti, S., Gianni, L., Valagussa, P.
(2005). 30 years' follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ
330: 217-
[Abstract][Full Text]
Dunn, B. K., Wickerham, D. L., Ford, L. G.
(2005). Prevention of Hormone-Related Cancers: Breast Cancer. JCO
23: 357-367
[Abstract][Full Text]
International Breast Cancer Study Group,
(2004). Toremifene and tamoxifen are equally effective for early-stage breast cancer: first results of International Breast Cancer Study Group Trials 12-93 and 14-93. Ann Oncol
15: 1749-1759
[Abstract][Full Text]
Schott, A., Hayes, D. F.
(2004). Adjuvant Chemotherapy for Elderly Women With Hormone Receptor-Positive Breast Cancer: An Old(er) Problem. JCO
22: 4660-4662
[Full Text]
Cristofanilli, M., Hortobagyi, G. N.
(2004). Breast Cancer Highlights: Key Findings from the San Antonio Breast Cancer Symposium: A U.S. Perspective. The Oncologist
9: 471-478
[Abstract][Full Text]
Bonadonna, G., Zambetti, M., Moliterni, A., Gianni, L., Valagussa, P.
(2004). Clinical Relevance of Different Sequencing of Doxorubicin and Cyclophosphamide, Methotrexate, and Fluorouracil in Operable Breast Cancer. JCO
22: 1614-1620
[Abstract][Full Text]
Cuzick, J., Buzdar, A., Baum, M., Bianco, R., Coleman, R., Constenla, M., Distler, W., Dowsett, M., Forbes, J., Guastalla, J. P., Houghton, J., Williams, N., Howell, A., Locker, G., MacKey, J., Sainsbury, R., Tobias, J.
(2004). Adjuvant Use of Anastrozole in Breast Cancer. JCO
22: 1524-1526
[Full Text]
Buzdar, A. U.
(2004). Data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial: Implications for Use of Aromatase Inhibitors in 2003. Clin. Cancer Res.
10: 355S-361S
[Abstract][Full Text]
de Haes, H., Olschewski, M., Kaufmann, M., Schumacher, M., Jonat, W., Sauerbrei, W.
(2003). Quality of Life in Goserelin-Treated Versus Cyclophosphamide + Methotrexate + Fluorouracil-Treated Premenopausal and Perimenopausal Patients With Node-Positive, Early Breast Cancer: The Zoladex Early Breast Cancer Research Association Trialists Group. JCO
21: 4510-4516
[Abstract][Full Text]
Lyman, G. H., Dale, D. C., Crawford, J.
(2003). Incidence and Predictors of Low Dose-Intensity in Adjuvant Breast Cancer Chemotherapy: A Nationwide Study of Community Practices. JCO
21: 4524-4531
[Abstract][Full Text]
Boyd, D. B.
(2003). Integrative Tumor Board: Recurrent Breast Cancer or New Primary?. Integr Cancer Ther
2: 270-272
Martin, M., Villar, A., Sole-Calvo, A., Gonzalez, R., Massuti, B., Lizon, J., Camps, C., Carrato, A., Casado, A., Candel, M. T., Albanell, J., Aranda, J., Munarriz, B., Campbell, J., Diaz-Rubio, E.
(2003). Doxorubicin in combination with fluorouracil and cyclophosphamide (i.v. FAC regimen, day 1, 21) versus methotrexate in combination with fluorouracil and cyclophosphamide (i.v. CMF regimen, day 1, 21) as adjuvant chemotherapy for operable breast cancer: a study by the GEICAM group. Ann Oncol
14: 833-842
[Abstract][Full Text]
Bernard-Marty, C., Mano, M., Paesmans, M., Accettura, C., Munoz-Bermeo, R., Richard, T., Kleiber, K., Cardoso, F., Lobelle, J. P., Larsimont, D., Piccart, M. J., Di Leo, A.
(2003). Second malignancies following adjuvant chemotherapy: 6-year results from a Belgian randomized study comparing cyclophosphamide, methotrexate and 5-fluorouracil (CMF) with an anthracycline-based regimen in adjuvant treatment of node-positive breast cancer patients. Ann Oncol
14: 693-698
[Abstract][Full Text]
Pater, J. L., Pritchard, K. I.
(2003). Optimal Chemotherapy for Women With Breast Cancer: The Plot Thickens. JCO
21: 963-964
[Full Text]
Pritchard, K. I.
(2002). Adjuvant Therapy for Premenopausal Women With Breast Cancer: Is It Time for Another Paradigm Shift?. JCO
20: 4611-4614
[Full Text]
Jonat, W., Kaufmann, M., Sauerbrei, W., Blamey, R., Cuzick, J., Namer, M., Fogelman, I., de Haes, J. C., de Matteis, A., Stewart, A., Eiermann, W., Szakolczai, I., Palmer, M., Schumacher, M., Geberth, M., Lisboa, B.
(2002). Goserelin Versus Cyclophosphamide, Methotrexate, and Fluorouracil as Adjuvant Therapy in Premenopausal Patients With Node-Positive Breast Cancer: The Zoladex Early Breast Cancer Research Association Study. JCO
20: 4628-4635
[Abstract][Full Text]
Mariotto, A., Feuer, E. J., Harlan, L. C., Wun, L.-M., Johnson, K. A., Abrams, J.
(2002). Trends in Use of Adjuvant Multi-Agent Chemotherapy and Tamoxifen for Breast Cancer in the United States: 1975-1999. JNCI J Natl Cancer Inst
94: 1626-1634
[Abstract][Full Text]
Arriagada, R., Spielmann, M., Koscielny, S., Le Chevalier, T., Delozier, T., Ducourtieux, M., Tursz, T., Hill, C.
(2002). Patterns of failure in a randomized trial of adjuvant chemotherapy in postmenopausal patients with early breast cancer treated with tamoxifen. Ann Oncol
13: 1378-1386
[Abstract][Full Text]
Zelek, L., Cottu, P., Tubiana-Hulin, M., Vannetzel, J.-M., Chollet, Ph., Misset, J.-L., Chouaki, N., Marty, M., Gamelin, E., Culine, S., Dieras, V., Mackenzie, S., Spielmann, M.
(2002). Phase II Study of Oxaliplatin and Fluorouracil in Taxane- and Anthracycline-Pretreated Breast Cancer Patients. JCO
20: 2551-2558
[Abstract][Full Text]
Ferreira Filho, A. F., Di Leo, A., Paesmans, M., Beauduin, M., Vindevoghel, A., Michel, J., Focan, C., Awada, A., Cardoso, F., Dolci, S., Bartholomeus, S., Piccart, M. J.
(2002). The feasibility of classical cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for pre- and post-menopausal node-positive breast cancer patients in a Belgian multicentric trial: a study of consistency in relative dose intensity (RDI) and cumulative doses across institutions. Ann Oncol
13: 416-421
[Abstract][Full Text]
Goodwin, P. J., Ennis, M., Pritchard, K. I., Trudeau, M. E., Koo, J., Madarnas, Y., Hartwick, W., Hoffman, B., Hood, N.
(2002). Fasting Insulin and Outcome in Early-Stage Breast Cancer: Results of a Prospective Cohort Study. JCO
20: 42-51
[Abstract][Full Text]
Hortobagyi, G. N
(2001). Progress in Systemic Chemotherapy of Primary Breast Cancer: an Overview. J Natl Cancer Inst Monogr
2001: 72-79
[Abstract][Full Text]
Yamauchi, H., Stearns, V., Hayes, D. F.
(2001). When Is a Tumor Marker Ready for Prime Time? A Case Study of c-erbB-2 as a Predictive Factor in Breast Cancer. JCO
19: 2334-2356
[Abstract][Full Text]
Ackland, S. P., Anton, A., Breitbach, G. P., Colajori, E., Tursi, J. M., Delfino, C., Efremidis, A., Ezzat, A., Fittipaldo, A., Kolaric, K., Lopez, M., Viaro, D.
(2001). Dose-Intensive Epirubicin-Based Chemotherapy Is Superior to an Intensive Intravenous Cyclophosphamide, Methotrexate, and Fluorouracil Regimen in Metastatic Breast Cancer: A Randomized Multinational Study. JCO
19: 943-953
[Abstract][Full Text]
Fisher, B., Dignam, J., Tan-Chiu, E., Anderson, S., Fisher, E. R., Wittliff, J. L., Wolmark, N.
(2001). Prognosis and Treatment of Patients With Breast Tumors of One Centimeter or Less and Negative Axillary Lymph Nodes. JNCI J Natl Cancer Inst
93: 112-120
[Abstract][Full Text]
Menard, S., Valagussa, P., Pilotti, S., Gianni, L., Biganzoli, E., Boracchi, P., Tomasic, G., Casalini, P., Marubini, E., Colnaghi, M. I., Cascinelli, N., Bonadonna, G.
(2001). Response to Cyclophosphamide, Methotrexate, and Fluorouracil in Lymph Node-Positive Breast Cancer According to HER2 Overexpression and Other Tumor Biologic Variables. JCO
19: 329-335
[Abstract][Full Text]
Simpson, J. F., Gray, R., Dressler, L. G., Cobau, C. D., Falkson, C. I., Gilchrist, K. W., Pandya, K. J., Page, D. L., Robert, N. J.
(2000). Prognostic Value of Histologic Grade and Proliferative Activity in Axillary Node-Positive Breast Cancer: Results From the Eastern Cooperative Oncology Group Companion Study, EST 4189. JCO
18: 2059-2069
[Abstract][Full Text]
Hortobagyi, G. N., Buzdar, A. U., Theriault, R. L., Valero, V., Frye, D., Booser, D. J., Holmes, F. A., Giralt, S., Khouri, I., Andersson, B., Gajewski, J. L., Rondon, G., Smith, T. L., Singletary, S. E., Ames, F. C., Sneige, N., Strom, E. A., McNeese, M. D., Deisseroth, A. B., Champlin, R. E.
(2000). Randomized Trial of High-Dose Chemotherapy and Blood Cell Autografts for High-Risk Primary Breast Carcinoma. JNCI J Natl Cancer Inst
92: 225-233
[Abstract][Full Text]
Colleoni, M., Bonetti, M., Coates, A. S., Castiglione-Gertsch, M., Gelber, R. D., Price, K., Rudenstam, C.-M., Lindtner, J., Collins, J., Thurlimann, B., Holmberg, S., Veronesi, A., Marini, G., Goldhirsch, A.
(2000). Early Start of Adjuvant Chemotherapy May Improve Treatment Outcome for Premenopausal Breast Cancer Patients With Tumors not Expressing Estrogen Receptors. JCO
18: 584-584
[Abstract][Full Text]
Braeuning, M. P., Burke, E. T., Pisano, E. D.
(2000). Embolization Coils as Tumor Markers for Mammography in Patients Undergoing Neoadjuvant Chemotherapy for Carcinoma. Am. J. Roentgenol.
174: 251-252
[Full Text]
Chu, K. C., Tarone, R. E., Brawley, O. W.
(1999). Breast Cancer Trends of Black Women Compared With White Women. Arch Fam Med
8: 521-528
[Abstract][Full Text]
Goodwin, P. J., Ennis, M., Pritchard, K. I., Trudeau, M., Hood, N.
(1999). Risk of Menopause During the First Year After Breast Cancer Diagnosis. JCO
17: 2365-2365
[Abstract][Full Text]
Goodwin, P. J., Ennis, M., Pritchard, K. I., McCready, D., Koo, J., Sidlofsky, S., Trudeau, M., Hood, N., Redwood, S.
(1999). Adjuvant Treatment and Onset of Menopause Predict Weight Gain After Breast Cancer Diagnosis. JCO
17: 120-120
[Abstract][Full Text]
Esteva, F. J., Hortobagyi, G. N.
(1998). Integration of Systemic Chemotherapy in the Management of Primary Breast Cancer. The Oncologist
3: 300-313
[Abstract][Full Text]
Foote, M.
(1998). The Importance of Planned Dose of Chemotherapy on Time: Do We Need to Change Our Clinical Practice?. The Oncologist
3: 365-368
[Full Text]
El-Tamer, M., Homel, P., Braverman, A. S., Wolberg, W. H., Robins, H. I., Goldhirsch, A., Coates, A. S., Colleoni, M., Gelber, R. D., Raffle, A.E., Evans, R. A., Overgaard, M., Rose, C., Mouridsen, H., Ragaz, J., Jackson, S. M., Spinelli, J. J., Hellman, S.
(1998). Radiotherapy and Chemotherapy in High-Risk Breast Cancer. NEJM
338: 329-333
[Full Text]
Ragaz, J., Jackson, S. M., Le, N., Plenderleith, I. H., Spinelli, J. J., Basco, V. E., Wilson, K. S., Knowling, M. A., Coppin, C. M.L., Paradis, M., Coldman, A. J., Olivotto, I. A.
(1997). Adjuvant Radiotherapy and Chemotherapy in Node-Positive Premenopausal Women with Breast Cancer. NEJM
337: 956-962
[Abstract][Full Text]
Valero, V., Buzdar, A. U., Hortobagyi, G. N.
(1996). Locally Advanced Breast Cancer. The Oncologist
1: 8-17
[Abstract][Full Text]
Bonadonna, G., Valagussa, P., Moliterni, A., Zambetti, M., Brambilla, C.
(1995). Adjuvant Cyclophosphamide, Methotrexate, and Fluorouracil in Node-Positive Breast Cancer -- The Results of 20 Years of Follow-Up. NEJM
332: 901-906
[Abstract][Full Text]
Henderson, I. C.
(1995). Paradigmatic Shifts in the Management of Breast Cancer. NEJM
332: 951-952
[Full Text]
Muller, H.-J., Gleiter, C. H., Gundert-Remy, U., Melnychuk, D., Panasci, L. C., Coppin, C. M.L., Goldie, J. H., Sauter, C., Garey, J., Lehrer, S., Farkas, D. H., Umek, R. M., Morrison, B. W., Atkins, C. D., Wood, W. C., Budman, D., Henderson, I. C., Muss, H. B., Thor, A. D., Berry, D. A., Goldhirsch, A., Gelber, R. D.
(1994). Adjuvant Therapy for Breast Cancer. NEJM
331: 741-746
[Full Text]
Olivotto, I. A., Bajdik, C. D., Plenderleith, I. H., Coppin, C. M., Gelmon, K. A., Jackson, S. M., Ragaz, J., Wilson, K. S., Worth, A.
(1994). Adjuvant Systemic Therapy and Survival after Breast Cancer. NEJM
330: 805-810
[Abstract][Full Text]
HOLLAND, J. F.
(1976). Breast Cancer and Chemotherapy. Science
192: 1062-1063